Interference of globin genes with biomarker discovery for allograft rejection in peripheral blood samples.
Microarray technology is a powerful tool in the discovery of new biomarkers for disease. After solid organ transplantation, where the detection of rejection is usually made on invasive biopsies, it could be hypothesized that noninvasive transcriptional profiling of peripheral blood will reveal rejection-specific expression patterns from circulating immune cells. However, in kidney transplant rejection, the analysis of gene expression data in whole blood has proven difficult for detecting significant genes specific for acute graft rejection. Previous studies have demonstrated that the abundance of globin genes in whole blood may mask the underlying biological differences between whole blood samples. In the present study, we compared the gene expression profiles of peripheral blood of nine stable renal allograft recipients with seven matched patients having an ongoing acute renal transplant rejection, using four different protocols of preparation, amplification, and synthesis of cRNA or cDNA and hybridization on the Affymetrix platform. We demonstrated that the globin reduction method is not sufficient to unmask clinically relevant rejection-specific transcriptome profiles in whole blood. Applying an additional mathematical depletion of the globin genes improves the efficacy of globin reduction but cannot remove the confounding influence of globin gene hybridization. Sampling of peripheral blood leukocytes alone, without the confounding influence of globin mRNA, provides sensitive and specific peripheral signatures for graft rejection, with many of these signals overlapping with rejection-driven tissue (kidney)-specific signatures from matched biopsies. Similar applications may exist for array-based biomarker discovery for other diseases associated with changes in leukocyte trafficking, activation, or function.


Home-Based Telemental Health: A Proposed Privacy and Safety Protocol and Tool.
Objectives: To describe the development of a protocol and practical tool for the safe delivery of telemental health (TMH) services to the home. The COVID-19 pandemic forced providers to rapidly transition their outpatient practices to home-based TMH (HB-TMH) without existing protocols or tools to guide them. This experience underscored the need for a standardized privacy and safety tool as HB-TMH is expected to continue as a resource during future crises as well as to become a component of the routine mental health care landscape. Methods: The authors represent a subset of the Child and Adolescent Psychiatry Telemental Health Consortium. They met weekly through videoconferencing to review published safety standards of care, existing TMH guidelines for clinic-based and home-based services, and their own institutional protocols. They agreed on three domains foundational to the delivery of HB-TMH: environmental safety, clinical safety, and disposition planning. Through multiple iterations, they agreed upon a final Privacy and Safety Protocol for HB-TMH. The protocol was then operationalized into the Privacy and Safety Assessment Tool (PSA Tool) based on two keystone medical safety constructs: the World Health Organization (WHO) Surgical Safety Checklist/Time-Out and the Checklist Manifesto.Results: The PSA Tool comprised four modules: (1) Screening for Safety for HB-TMH; (2) Assessment for Safety During the HB-TMH Initial Visit; (3) End of the Initial Visit and Disposition Planning; and (4) the TMH Time-Out and Reassessment during subsequent visits. A sample workflow guides implementation. Conclusions: The Privacy and Safety Protocol and PSA Tool aim to prepare providers for the private and safe delivery of HB-TMH. Its modular format can be adapted to each site's resources. Going forward, the PSA Tool should help to facilitate the integration of HB-TMH into the routine mental health care landscape.


Grazing incidence tomography.
The potentialities of photographic transaxial tomographic methods are discussed. It is shown that unfiltered, transaxial tomographic summation images can yield high-quality tomograms of high-contrast objects. A direct and efficient photographic method for recording transaxial tomograms (grazing incidence tomography) is demonstrated, and various means for analog filtering are discussed. Grazing incidence tomography allows for high geometrical resolution for high- or medium-contrast objects. The present contrast performance is an order of magnitude different to that of computerised tomography, but an improvement of the method seems possible.


Detecting Acceleration-Enhanced Vacuum Fluctuations with Atoms Inside a Cavity.
Some of the most prominent theoretical predictions of modern times, e.g., the Unruh effect, Hawking radiation, and gravity-assisted particle creation, are supported by from the fact that various quantum constructs like particle content and vacuum fluctuations of a quantum field are observer-dependent. Despite being fundamental in nature, these predictions have not yet been experimentally verified because one needs extremely strong gravity (or acceleration) to bring them within the existing experimental resolution. In this Letter, we demonstrate that a post-Newtonian rotating atom inside a far-detuned cavity experiences strongly modified quantum fluctuations in the inertial vacuum. As a result, the emission rate of an excited atom gets enhanced significantly along with a shift in the emission spectrum due to the change in the quantum correlation under rotation. We propose an optomechanical setup that is capable of realizing such acceleration-induced particle creation with current technology. This provides a novel and potentially feasible experimental proposal for the direct detection of noninertial quantum field theoretic effects.


Effects of viral chemotherapeutic agents on membrane properties. Studies of cyclosporin A, benzyloxycarbonyl-D-Phe-L-Phe-Gly and amantadine.
Cyclosporin A, benzyloxycarbonyl-D-Phe-L-Phe-Gly, and amantadine inhibit the dilution of fluorescently labeled lipids, as measured with the resonance energy exchange assay for membrane fusion. The fusion was studied using sonicated vesicles containing 1,2-dioleoyl-sn-glycero(3)phosphoethanolamine, egg (3-sn-phosphatidyl)choline, and cholesterol in a 1:1:1.3 molar ratio. All three antiviral agents inhibited myelin basic protein-induced membrane fusion when present at low concentrations in the membrane. The mechanism by which these agents affect membrane properties was investigated. The effect of these agents on the bilayer to hexagonal phase transition of 1,2-dielaidoyl-sn-glycero(3)phosphoethanolamine was determined using both differential scanning calorimetry and 31P NMR. Benzyloxycarbonyl-D-Phe-L-Phe-Gly is particularly effective in raising the bilayer to hexagonal phase transition temperature while cyclosporin promotes the greatest amount of broadening of the 31P NMR signal. Both effects are suggested to be related to the inhibitory activity of these substances on membrane fusion and possibly also to their antiviral activity.


Femtosecond resolution of soft mode dynamics in structural phase transitions.
The microscopic pathway along which ions or molecules in a crystal move during a structural phase transition can often be described in terms of a collective vibrational mode of the lattice. In many cases, this mode, called a "soft" phonon mode because of its characteristically low frequency near the phase transition temperature, is difficult to characterize through conventional frequency-domain spectroscopies such as light or neutron scattering. A femtosecond time-domain analog of light-scattering spectroscopy called impulsive stimulated Raman scattering (ISRS) has been used to examine the soft modes of two perovskite ferroelectric crystals. The low-frequency lattice dynamics of KNbO(3) and BaTiO(3) are clarified in a manner that permits critical evaluation of microscopic models for their ferroelectric transitions. The results illustrate the advantages of ISRS over conventional Raman spectroscopy of low-frequency, heavily damped soft modes.


Optofluidic Single-Cell Genome Amplification of Sub-micron Bacteria in the Ocean Subsurface.
Optofluidic single-cell genome amplification was used to obtain genome sequences from sub-micron cells collected from the euphotic and mesopelagic zones of the northwestern Sargasso Sea. Plankton cells were visually selected and manually sorted with an optical trap, yielding 20 partial genome sequences representing seven bacterial phyla. Two organisms, E01-9C-26 (Gammaproteobacteria), represented by four single cell genomes, and Opi.OSU.00C, an uncharacterized Verrucomicrobia, were the first of their types retrieved by single cell genome sequencing and were studied in detail. Metagenomic data showed that E01-9C-26 is found throughout the dark ocean, while Opi.OSU.00C was observed to bloom transiently in the nutrient-depleted euphotic zone of the late spring and early summer. The E01-9C-26 genomes had an estimated size of 4.76-5.05 Mbps, and contained "O" and "W"-type monooxygenase genes related to methane and ammonium monooxygenases that were previously reported from ocean metagenomes. Metabolic reconstruction indicated E01-9C-26 are likely versatile methylotrophs capable of scavenging C1 compounds, methylated compounds, reduced sulfur compounds, and a wide range of amines, including D-amino acids. The genome sequences identified E01-9C-26 as a source of "O" and "W"-type monooxygenase genes related to methane and ammonium monooxygenases that were previously reported from ocean metagenomes, but are of unknown function. In contrast, Opi.OSU.00C genomes encode genes for catabolizing carbohydrate compounds normally associated with eukaryotic phytoplankton. This exploration of optofluidics showed that it was effective for retrieving diverse single-cell bacterioplankton genomes and has potential advantages in microbiology applications that require working with small sample volumes or targeting cells by their morphology.


Viable and Total Bacterial Populations Undergo Equipment- and Time-Dependent Shifts during Milk Processing.
We set out to identify the viable and total bacterial content in milk as it passes through a large-scale, dairy product manufacturing plant for pasteurization, concentration, separation, blending, and storage prior to cheese manufacture. A total of 142 milk samples were collected from up to 10 pieces of equipment for a period spanning 21 h on two collection dates in the spring and late summer of 2014. Bacterial composition in the milk was determined by 16S rRNA marker gene, high-throughput DNA sequencing. Milk samples from the late summer were paired such that half were treated with propidium monoazide (PMA) to enrich for viable cells prior to quantification by PCR and identification by DNA sequence analysis. Streptococcus had the highest median relative abundance across all sampling sites within the facility on both sampling dates. The proportions of Anoxybacillus, Thermus, Lactococcus, Lactobacillus, Micrococcaceae, and Pseudomonas were also elevated in some samples. Viable cells detected by PMA treatment showed that Turicibacter was enriched after high-temperature short-time pasteurization, whereas proportions of Staphylococcus were significantly reduced. Using clean-in-place (CIP) times as a reference point, Bacillus, Pseudomonas, and Anoxybacillus were found in high relative proportions in several recently cleaned silos (<19 h since CIP). At later times (>19 h after CIP), 10 of 11 silos containing elevated viable cell numbers were enriched in Acinetobacter and/or Lactococcus These results show the tremendous point-to-point and sample-dependent variations in bacterial composition in milk during processing.IMPORTANCE Milk undergoes sustained contact with the built environment during processing into finished dairy products. This contact has the potential to influence the introduction, viability, and growth of microorganisms within the milk. Currently, the population dynamics of bacteria in milk undergoing processing are not well understood. Therefore, we measured for total and viable bacterial composition and cell numbers in milk over time and at different processing points in a cheese manufacturing facility in California. Our results provide new perspectives on the dramatic variations in microbial populations in milk during processing even over short amounts of time. Although some of the changes in the milk microbiota were predictable (e.g., reduced viable cell numbers after pasteurization), other findings could not be easily foreseen based on knowledge of bacteria contained in raw milk or when the equipment was last cleaned. This information is important for predicting and controlling microbial spoilage contaminants in dairy products.


Sphingosine kinase 1 is required for TGF-β mediated fibroblastto- myofibroblast differentiation in ovarian cancer.
Sphingosine kinase 1 (SPHK1), the enzyme that produces sphingosine 1 phosphate (S1P), is known to be highly expressed in many cancers. However, the role of SPHK1 in cells of the tumor stroma remains unclear. Here, we show that SPHK1 is highly expressed in the tumor stroma of high-grade serous ovarian cancer (HGSC), and is required for the differentiation and tumor promoting function of cancer-associated fibroblasts (CAFs). Knockout or pharmacological inhibition of SPHK1 in ovarian fibroblasts attenuated TGF-β-induced expression of CAF markers, and reduced their ability to promote ovarian cancer cell migration and invasion in a coculture system. Mechanistically, we determined that SPHK1 mediates TGF-β signaling via the transactivation of S1P receptors (S1PR2 and S1PR3), leading to p38 MAPK phosphorylation. The importance of stromal SPHK1 in tumorigenesis was confirmed in vivo, by demonstrating a significant reduction of tumor growth and metastasis in SPHK1 knockout mice. Collectively, these findings demonstrate the potential of SPHK1 inhibition as a novel stroma-targeted therapy in HGSC.


What do monkeys know about others' knowledge?
Recently, comparative psychologists have suggested that primates represent others' knowledge states. Evidence for this claim comes from studies demonstrating that primates expect others to maintain representations of objects when those objects are not currently visible. However, little work has explored whether nonhuman primates expect others to share the more sophisticated kinds of object knowledge that they themselves possess. We therefore investigated whether primates attribute to others knowledge that is acquired through the mental transformation of a static object representation. Specifically, we tested whether rhesus macaques (Macaca mulatta) expected a human demonstrator to solve a difficult rotational displacement task. In Experiment 1, monkeys watched a demonstrator hide a piece of fruit in one of two boxes. The monkey and the demonstrator then watched the boxes rotate 180°. We found that monkeys looked longer when the demonstrator reached into the box that did not contain the fruit, indicating that they expected her to be able to track the fruit to its current location. In Experiment 2, we ruled out the possibility that monkeys simply expected the demonstrator to search for the food in its true location. When the demonstrator did not witness the rotation event, monkeys looked equally long at the two reaching outcomes. These results are consistent with the interpretation that rhesus macaques expect others to dynamically update their representations of unseen objects.


The Scale of Functional Specialization within Human Prefrontal Cortex.
At what scale is it possible to observe consistent functional specialization within human prefrontal cortex (PFC), reproducible from one individual to the next? Some studies suggest gross functional divisions between large regions of PFC, but it is not known whether PFC exhibits specialization at the fine-grained scale known to differentiate posterior cortical functions. We used fMRI to confirm a three-way segregation of function between three regions of medial anterior PFC, each centered on coordinates within 15 mm of the other two. Naive participants performed three tasks based on earlier studies, and we investigated activity at regions defined by previous results. In each task, signal was significantly greater at the predicted region than the other two, just millimeters away. These results indicate reproducible functional specialization within PFC, at a much finer scale than previously demonstrated. Furthermore, these findings suggest that divergent results from previous studies may reflect the recruitment of functionally distinct regions and that "reverse inference" should be undertaken with caution.


Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis.
Recombinant forms of Neisseria meningitidis human factor H binding protein (fHBP) are undergoing clinical trials in candidate vaccines against invasive meningococcal serogroup B disease. We report an extensive survey and phylogenetic analysis of the diversity of fhbp genes and predicted protein sequences in invasive clinical isolates obtained in the period 2000-2006. Nucleotide sequences of fhbp genes were obtained from 1837 invasive N. meningitidis serogroup B (MnB) strains from the United States, Europe, New Zealand, and South Africa. Multilocus sequence typing (MLST) analysis was performed on a subset of the strains. Every strain contained the fhbp gene. All sequences fell into 1 of 2 subfamilies (A or B), with 60%-75% amino acid identity between subfamilies and at least 83% identity within each subfamily. One fHBP sequence may have arisen via inter-subfamily recombination. Subfamily B sequences were found in 70% of the isolates, and subfamily A sequences were found in 30%. Multiple fHBP variants were detected in each of the common MLST clonal complexes. All major MLST complexes include strains in both subfamily A and subfamily B. The diversity of strains observed underscores the importance of studying the distribution of the vaccine antigen itself rather than relying on common epidemiological surrogates such as MLST.


Impact of hospital volume on perioperative outcomes and costs of radical cystectomy: analysis of the Maryland Health Services Cost Review Commission database.
The objective of this study was to evaluate the impact of hospital case volume on perioperative outcomes and costs of radical cystectomy (RC) after controlling for differences in patient case mix. The Maryland Health Services Cost Review Commission database was queried for patients who underwent an open RC between 2000 and 2011. Patients were divided into tertiles based on hospital case volume. Groups were compared for differences in length of intensive care unit (ICU) stay, length of total hospital stay, rate of in-hospital deaths and procedure-related costs. In total, 1620 patients underwent a RC during the study period. Of these patients, 457 (28.2%) underwent surgery at 37 low volume centers, 465 (28.7%) at six mid volume centers and 698 (43.1%) at a single high volume center. The mean case volume of each group was 1.1, 7.0 and 63.5 RC/center/year, respectively. After controlling for marked differences in patient case mix, having surgery at the single high-volume center was independently associated with a decrease in length of ICU stay (coefficient = -0.41 days, 95% CI -0.78--0.05, p = 0.03), in-hospital mortality (OR 0.18, 95% CI 0.04-0.80, p = 0.02) and total medical costs (coefficient = -2.91k USD, 95% CI -4.15--1.67, p < 0.001). Decreased total costs were driven by reductions in charges associated with the operating room, drugs, radiology tests, labs, supplies and physical/occupational therapy (all p < 0.001). Undergoing RC at a high volume medical center was associated with improved outcomes and reduced costs. These data support the centralization of RC to high volume centers.


Alteration of gene expression induced by Silurus asotus lectin in Burkitt's lymphoma cells.
Silurus asotus lectin (SAL) is a member of the rhamnose-binding lectin (RBL) family, and recognizes globotriaosylceramide (Gb3) on the cell surface of Burkitt's lymphoma cell lines, such as Raji and Daudi cells. The variation of gene expression in the treatment of both cells with SAL was analyzed using the differential display (DD) method with combination of 16 kinds of arbitary primers and 3 kinds of anchor primers. Treatment of Raji cells with SAL down-regulated mitochondria-associated granulocyte-macropharge colony-stimulating factor (GM-CSF) signaling molecule (Magmas) gene, and up-regulated N-myc downstream regulated gene (NDRG) 3. On the other hand, treatment of Daudi cells with SAL down-regulated Rad50 gene. Since Magmas gene expression was repressed in SAL-treated Raji cells, but did not change in SAL-treated D-threo-1-phenyl-2-decanoylamino-3-morphorino-1-propanol (PDMP)-pretreated Raji cells, it was clear that the expression of Magmas, NDRG3 or Rad50 was regulated by SAL binding to Gb3.


Anaerobic methane oxidation in a landfill-leachate plume.
The alluvial aquifer adjacent to Norman Landfill, OK, provides an excellent natural laboratory for the study of anaerobic processes impacting landfill-leachate contaminated aquifers. We collected groundwaters from a transect of seven multilevel wells ranging in depth from 1.3 to 11 m that were oriented parallel to the flow path. The center of the leachate plume was characterized by (1) high alkalinity and elevated concentrations of total dissolved organic carbon, reduced iron, and methane, and (2) negligible oxygen, nitrate, and sulfate concentrations. Methane concentrations and stable carbon isotope (delta13C) values suggest anaerobic methane oxidation was occurring within the plume and at its margins. Methane delta13C values increased from about -54 per thousand near the source to > -10 per thousand downgradient and at the plume margins. The isotopic fractionation associated with this methane oxidation was -13.6+/-1.0 per thousand. Methane 13C enrichment indicated that 80-90% of the original landfill methane was oxidized over the 210-m transect. First-order rate constants ranged from 0.06 to 0.23 per year, and oxidation rates ranged from 18 to 230 microM/y. Overall, hydrochemical data suggest that a sulfate reducer-methanogen consortium may mediate this methane oxidation. These results demonstrate that natural attenuation through anaerobic methane oxidation can be an important sink for landfill methane in aquifer systems.


Multi-atlas based segmentation using probabilistic label fusion with adaptive weighting of image similarity measures.
Label fusion multi-atlas approaches for image segmentation can give better segmentation results than single atlas methods. We present a multi-atlas label fusion strategy based on probabilistic weighting of distance maps. Relationships between image similarities and segmentation similarities are estimated in a learning phase and used to derive fusion weights that are proportional to the probability for each atlas to improve the segmentation result. The method was tested using a leave-one-out strategy on a database of 21 pre-segmented prostate patients for different image registrations combined with different image similarity scorings. The probabilistic weighting yields results that are equal or better compared to both fusion with equal weights and results using the STAPLE algorithm. Results from the experiments demonstrate that label fusion by weighted distance maps is feasible, and that probabilistic weighted fusion improves segmentation quality more the stronger the individual atlas segmentation quality depends on the corresponding registered image similarity. The regions used for evaluation of the image similarity measures were found to be more important than the choice of similarity measure.


Acute hypertensive stress imaged by cardiac hyperpolarized [1-13 C]pyruvate magnetic resonance.
Deranged metabolism is now recognized as a key causal factor in a variety of heart diseases, and is being studied extensively. However, invasive methods may alter metabolism, and conventional imaging techniques measure tracer uptake but not downstream metabolism. These challenges may be overcome by hyperpolarized MR, a noninvasive technique currently crossing the threshold into human trials. The aim of this study was to image metabolic changes in the heart in response to endogastric glucose bolus and to acute hypertension. Five postprandial pigs were scanned with hyperpolarized [1-13 C]pyruvate cardiac MR at baseline, after oral glucose bolus, and after infusion of angiotensin-II. No effect of glucose bolus was seen using hyperpolarized [1-13 C]pyruvate MR despite changes in circulating substrates. During angiotensin-II infusion, blood pressure increased 179% (P = 0.008) and ejection fraction decreased from 54 ± 2% to 47 ± 6% (P = 0.03) The hemodynamic changes were accompanied by increases in the hyperpolarized [1-13 C]pyruvate MR derived ratios of lactate/alanine (from 0.58 ± 0.13 to 0.78 ± 0.06, P = 0.03) and bicarbonate/alanine (from 0.55 ± 0.12 to 0.91 ± 0.14, P = 0.007). Glucose loading did not alter cardiac metabolism, but during acute hypertensive stress, cardiac aerobic, carbohydrate metabolism, and pyruvate-lactate exchange was altered. Hyperpolarized MR allows noninvasive evaluation of acute changes in cardiac metabolism. However, hemodynamics must be taken into account when interpreting the results.


Two subpopulation of human Purkinje neurons: an electron microscopy study.
Conventional electron microscopy of human cerebellar cortex has revealed two types of Purkinje neurons with different staining intensities. The light-stained type constitute the major type and both types have similar diameters. This finding was not reported in human before but in lower mammalian. Whether the different staining pattern of Purkinje neurons implies a specific histo-functional aspect a pathological one or histological artifacts is not known.


Accuracy of implant placement with a stereolithographic surgical guide.
Placement of dental implants requires precise planning that accounts for anatomic limitations and restorative goals. Diagnosis can be made with the assistance of computerized tomographic (CT) scanning, but transfer of planning to the surgical field is limited. Recently, novel CAD/CAM techniques such as stereolithographic rapid prototyping have been developed to build surgical guides in an attempt to improve precision of implant placement. However, comparison of these advanced techniques to traditional surgical guides has not been performed. The goal of this study was to compare the accuracy of a conventional surgical guide to that of a stereolithographic surgical guide. CT scanning of epoxy edentulous mandibles was performed using a cone beam CT scanner with high isotropic spatial resolution, while planning for 5 implants on each side of the jaw was performed using a commercially available software package. Five surgeons performed osteotomies on a jaw identical to the initial model; on the right side a conventional surgical guide (control side) was used, and on the left side a stereolithographic guide was used (test side). Each jaw was then CT scanned, and a registration method was applied to match it to the initial planning. Measurements included distances between planned implants and actual osteotomies. The average distance between the planned implant and the actual osteotomy was 1.5 mm at the entrance and 2.1 mm at the apex when the control guide was used. The same measurements were significantly reduced to 0.9 mm and 1.0 mm when the test guide was used. Variations were also reduced with the test guide, within surgeons and between surgeons. Surgical guidance for implant placement relieves the clinician from multiple perioperative decisions. Precise implant placement is under investigation using sophisticated guidance methods, including CAD/CAM templates. Within the limits of this study, implant placement was improved by using a stereolithographic surgical guide.


Effect of Light/Dark Cycle on Photosynthetic Pathway Switching and CO2 Absorption in Two Dendrobium Species.
Many Dendrobium species are both ornamental and medicinal plants in China. Several wild species have been exploited to near extinction, and facility cultivation has become an important way to meet the great market demand. Most Dendrobium species have evolved into crassulacean acid metabolism (CAM) pathways in adapting to harsh epiphytic environment, leading to low daily net CO2 absorption. Photosynthetic pathways of many facultative CAM plants are regulated by various environmental factors. Light/dark cycle plays an important role in regulating the photosynthetic pathway of several CAM species. The aims of this study were to investigate whether the photosynthetic pathway of Dendrobium species could be regulated between C3 and CAM by changing light/dark cycles and the daily net CO2 absorption could be enhanced by shortening light/dark cycle. In this study, net CO2 exchange rates of D. officinale and D. primulinum were monitored continuously during two different light/dark cycles conversion compared to Kalanchoe daigremontiana as an obligate CAM plant. The net CO2 exchange pattern and stomatal behavior of D. officinale and D. primulinum were switched from CAM to C3-like by changing the light/dark cycle from 12/12 h to 4/4 h. However, this switching was not completely reversible. Compared to the original 12/12 h light/dark cycle, the dark, light, and daily net CO2 exchange amount of D. officinale were significantly increased after the light/dark cycle was changed from 4/4 h to 12/12 h, but those in D. primulinum was opposite and those in K. daigremontiana was not affected. Daily net CO2 exchange amount of D. officinale increased by 47% after the light/dark cycle was changed from 12/12 h to 4/4 h, due to the sharp increase of light net CO2 exchange amount. However, the large decrease of dark net CO2 exchange amount could not be offset by increased light net CO2 exchange amount, leading to reduced daily net CO2 exchange amount of D. primulinum. In conclusion, the 4/4 h light/dark cycle can induce the photosynthetic pathway of D. officinale and D. primulinum to C3-like, and improve the daily CO2 absorption of D. officinale.


Binding of adult T-cell leukemia virus to various hematopoietic cells.
A newly found human retrovirus, adult T-cell leukemia virus (ATLV) was shown by means of membrane immunofluorescence to bind to various hematopoietic cells including T-, B- and non-T, non-B-cell lines. Partially purified viral gp46 from culture fluids of ATL virus producer lines also bound efficiently to an ATLV-negative T-cell line, CCRF-CEM cells. When the viruses were pre-incubated with anti-ATLV-positive human sera, ATLV binding to the cells was clearly inhibited but not by pre-incubation with anti-ATLV-negative sera. These data suggest that: (1) ATLV binds not only to T-cells but also to multiple types of cells of hematopoietic origin; (2) anti-ATLV antibody-positive human sera have the blocking antibody for the binding of ATLV to lymphoid cells.


Structure Integral Transform Versus Radon Transform: A 2D Mathematical Tool for Invariant Shape Recognition.
In this paper, we present a novel mathematical tool, Structure Integral Transform (SIT), for invariant shape description and recognition. Different from the Radon Transform (RT), which integrates the shape image function over a 1D line in the image plane, the proposed SIT builds upon two orthogonal integrals over a 2D K -cross dissecting structure spanning across all rotation angles by which the shape regions are bisected in each integral. The proposed SIT brings the following advantages over the RT: 1) it has the extra function of describing the interior structural relationship within the shape which provides a more powerful discriminative ability for shape recognition; 2) the shape regions are dissected by the K -cross in a coarse to fine hierarchical order that can characterize the shape in a better spatial organization scanning from the center to the periphery; and 3) it is easier to build a completely invariant shape descriptor. The experimental results of applying SIT to shape recognition demonstrate its superior performance over the well-known Radon transform, and the well-known shape contexts and the polar harmonic transforms.


Angiography of pheochromocytomas.
In 24 patients with a pheochromocytoma, angiography revealed a multiple localization in 20%, extra-adrenal localization in 20%, and insufficient information supplied by aortography in 25%. On the basis of this experience, several proposals are advanced for optimal execution of the vascular study, including retrograde phlebography of apparently normal adrenal glands and application of the subtraction technique.


Interactive Effect of Ethnicity and ACE Insertion/Deletion Polymorphism on Vascular Reactivity.
-Bradykinin is a potent endothelium-dependent vasodilator that contributes to the blood pressure lowering effect of angiotensin-converting enzyme inhibition. Angiotensin-converting enzyme inhibitors are widely prescribed for the treatment of hypertension, although the efficacy of this therapy has been reported to vary among different ethnic groups. To determine whether vascular sensitivity to bradykinin is decreased in blacks compared with whites, we measured forearm blood flow with venous plethysmography in response to intraarterially-administered bradykinin (100, 200, and 400 ng/min) under salt-controlled conditions in 28 (14 black, 14 white) normotensive subjects genotyped for the ACE insertion/deletion (I:/D) polymorphism. Acetylcholine (ACh) (15, 30, and 60 µg/min) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 µg/min) were infused as endothelium-dependent and endothelium-independent controls. Compared with whites, blacks exhibited a blunted vasodilator response to bradykinin (maximal blood flow: 20.4+/-2.5 versus 10.9+/-1.4 mL. 100 mL(-1). min(-1), P:=0.004) and SNP (14.1+/-1.6 versus 9.9+/-1.7 mL. 100 mL(-1). min(-1), P:=0.05) but not to ACh (10.5+/-2.8 versus 6.6+/-1.0 mL. 100 mL(-1). min(-1), P:=0.21). White subjects who carried at least 1 ACE D allele demonstrated significantly greater vasodilator responses to bradykinin compared with those homozygous for the I: allele (DD or I:D versus I:I, F=5.6, P:<0.04). In contrast, only blacks homozygous for the ACE D allele had a significantly greater vasodilator response to bradykinin than those who carried the I: allele (DD versus ID or II, F=8.3, P:=0.01). The ethnic difference was most pronounced in subjects heterozygous at the ACE I/D locus in which blacks had a markedly attenuated response to bradykinin compared with whites (F=41.0, P:<0.001). There was no effect of ACE I/D genotype on the vasodilator responses to SNP or ACh in either ethnic group. These data confirm that vascular reactivity to bradykinin and the endothelium-independent vasodilator SNP is decreased in normotensive blacks compared with whites, consistent with attenuated vascular smooth muscle reactivity. The data suggest that genetic variation at the ACE gene locus interacts with ethnicity to impact the vascular response to bradykinin.


Disposable surface plasmon resonance aptasensor with membrane-based sample handling design for quantitative interferon-gamma detection.
ELISA and ELISPOT methods are utilized for interferon-gamma (IFN-γ) release assays (IGRAs) to detect the IFN-γ secreted by T lymphocytes. However, the multi-step protocols of the assays are still performed with laboratory instruments and operated by well-trained people. Here, we report a membrane-based microfluidic device integrated with a surface plasmon resonance (SPR) sensor to realize an easy-to-use and cost effective multi-step quantitative analysis. To conduct the SPR measurements, we utilized a membrane-based SPR sensing device in which a rayon membrane was located 300 μm under the absorbent pad. The basic equation covering this type of transport is based on Darcy's law. Furthermore, the concentration of streptavidin delivered from a sucrose-treated glass pad placed alongside the rayon membrane was controlled in a narrow range (0.81 μM ± 6%). Finally, the unbound molecules were removed by a washing buffer that was pre-packed in the reservoir of the chip. Using a bi-functional, hairpin-shaped aptamer as the sensing probe, we specifically detected the IFN-γ and amplified the signal by binding the streptavidin. A high correlation coefficient (R(2) = 0.995) was obtained, in the range from 0.01 to 100 nM. A detection limit of 10 pM was achieved within 30 min. Thus, the SPR assay protocols for IFN-γ detection could be performed using this simple device without an additional pumping system.


Reproductive interference explains persistence of aggression between species.
Interspecific territoriality occurs when individuals of different species fight over space, and may arise spontaneously when populations of closely related territorial species first come into contact. But defence of space is costly, and unless the benefits of excluding heterospecifics exceed the costs, natural selection should favour divergence in competitor recognition until the species no longer interact aggressively. Ordinarily males of different species do not compete for mates, but when males cannot distinguish females of sympatric species, females may effectively become a shared resource. We model how reproductive interference caused by undiscriminating males can prevent interspecific divergence, or even cause convergence, in traits used to recognize competitors. We then test the model in a genus of visually orienting insects and show that, as predicted by the model, differences between species pairs in the level of reproductive interference, which is causally related to species differences in female coloration, are strongly predictive of the current level of interspecific aggression. Interspecific reproductive interference is very common and we discuss how it may account for the persistence of interspecific aggression in many taxonomic groups.


Problems in classification of cancer for epidemiologic research.
In vital statistics and most epidemiologic studies, cancers have been classified mostly by site of origin alone. This continues to be true even though it is continually being demonstrated that among cancers of a site important subsets with different epidemiologies almost always are present. Reasons for epidemiologists' failure to use all the information contained in the standard cancer classification are explored as are problems that arise from the nature of the classification, from the nature of the cancers being classified, and even from patient characteristics that determine how much information on the cancer can be gathered. The solution to the problem of too little information is generally difficult, but pathologists can say more about the epidemiologic implications of their various diagnoses and epidemiologists can learn to use these diagnoses in their cohort and other studies.


Mutational hot spots in Ig V region genes of human follicular lymphomas.
The genes coding for the Ig light chains expressed in two cases of human follicular lymphoma were cloned and sequenced. In each case, multiple independent isolates of the tumor population were compared. Although each tumor represented a single clone of B cells with a unique V/J joint, different cells within each tumor had accumulated multiple point mutations in the V gene during clonal expansion. Most of the mutations observed were silent, but some resulted in amino acid replacements. Identical silent mutations were often observed in independent isolates of each tumor. By combining the current data with VH sequences obtained previously from the same cells, it was apparent that the repetitive silent mutations could not be explained solely by a genealogic tree. Such mutations could represent hot spots whose tendency to mutate may be influenced by neighboring DNA sequences or by the methylation of specific cytosine residues.


C12ORF39, a novel secreted protein with a typical amidation processing signal.
In the present study we describe a novel secreted protein, named C12ORF39 (chromosome 12 open-reading framework 39), which contains a typical amidation/proteolytic processing signal (Gly-Arg-Arg motif). Interestingly, C12ORF39 protein is not hydrolysed, but is a full-length protein without signal peptides. Western blotting indicated that c-Myc-tagged C12ORF39 is secreted into culture medium in transfected HeLa cells. Quantitative RT-PCR (reverse transcription-PCR) analysis revealed that c12orf39 is mainly expressed in placenta and brain. Immunohistochemistry on formalin-fixed paraffin-embedded human term placenta using a rabbit antibody against human C12ORF39 demonstrated that the protein was localized extracellularly, surrounding the trophoblastic cells. In addition, C12ORF39 secretion could be blocked by brefeldin A, suggesting that the secretion of C12ORF39 is dependent on the Golgi apparatus. Furthermore, laser-scanning confocal microscopy also confirmed that the C12ORF39 protein co-localized with the Golgi apparatus. Taken together, although C12ORF39 is not a secreted small peptide, it can also be secreted to play a role in the biological functions of the placenta.


Forensic reporting of a case of sexual abuse broadcast on periscope.
Children who are investigated or prosecuted for an action that is considered a crime by the law, or children who were placed in security facilities due to his/her actions are defined as "children forced into crime". The period between ages 12-18 years is adolescence, during which crime rates are relatively high. The incidence of sexual behavior of adolescents on social media, which may be considered a crime, has increased in recent years due to technological improvements and increase in the use of social media. Also, the crime rates involving adolescents have increased due to environmental influences, familial factors, and mental disorders. Mental disorders such as conduct disorder, attention deficit hyperactivity disorder, and mood disorders have been found to be associated with sexual abuse in young persons in previous literature. In this study, we present the case of a boy who sexually abused his younger brother at the age of 14 years 2 months and broadcast this abuse on "Periscope". In this case study, we aimed to discuss the relationships between sexual abuse, social media, and psychiatric disorders.


Poultry, pig and the risk of BSE following the feed ban in France--a spatial analysis.
A spatial analysis was carried out in order to analyse the reason why the risk of Bovine Spongiform Encephalopathy (BSE) was spatially heterogeneous in France, during the period following the feed ban of Meat and Bone Meal to cattle. The hypothesis of cross-contamination between cattle feedstuff and monogastric feedstuff, which was strongly suggested from previous investigations, was assessed, with the assumption that the higher the pig or poultry density is in a given area, the higher the risk of cross-contamination and cattle infection might be. The data concerned the 467 BSE cases born in France after the ban of meat and bone meal (July 1990) and detected between July 1st, 2001 and December 31, 2003, when the surveillance system was optimal and not spatially biased. The disease mapping models were elaborated with the Bayesian graphical modelling methods and based on a Poisson distribution with spatial smoothing (hierarchical approach) and covariates. The parameters were estimated by a Markov Chain Monte Carlo simulation method. The main result was that the poultry density did not significantly influence the risk of BSE whereas the pig density was significantly associated with an increase in the risk of 2.4% per 10 000 pigs. The areas with a significant pig effect were located in regions with a high pig density as well as a high ratio of pigs to cattle. Despite the absence of a global effect of poultry density on the BSE risk, some areas had a significant poultry effect and the risk was better explained in some others when considering both pig and poultry densities. These findings were in agreement with the hypothesis of cross-contamination, which could take place at the feedstuff factory, during the shipment of food or on the farm. Further studies are needed to more precisely explore how the cross-contamination happened.


Lichens survive in space: results from the 2005 LICHENS experiment.
This experiment was aimed at establishing, for the first time, the survival capability of lichens exposed to space conditions. In particular, the damaging effect of various wavelengths of extraterrestrial solar UV radiation was studied. The lichens used were the bipolar species Rhizocarpon geographicum and Xanthoria elegans, which were collected above 2000 m in the mountains of central Spain and as endolithic communities inhabiting granites in the Antarctic Dry Valleys. Lichens were exposed to space in the BIOPAN-5 facility of the European Space Agency; BIOPAN-5 is located on the outer shell of the Earth-orbiting FOTON-M2 Russian satellite. The lichen samples were launched from Baikonur by a Soyuz rocket on May 31, 2005, and were returned to Earth after 16 days in space, at which time they were tested for survival. Chlorophyll fluorescence was used for the measurement of photosynthetic parameters. Scanning electron microscopy in back-scattered mode, low temperature scanning electron microscopy, and transmission electron microscopy were used to study the organization and composition of both symbionts. Confocal laser scanning microscopy, in combination with the use of specific fluorescent probes, allowed for the assessment of the physiological state of the cells. All exposed lichens, regardless of the optical filters used, showed nearly the same photosynthetic activity after the flight as measured before the flight. Likewise, the multimicroscopy approach revealed no detectable ultrastructural changes in most of the algal and fungal cells of the lichen thalli, though a greater proportion of cells in the flight samples had compromised membranes, as revealed by the LIVE/DEAD BacLight Bacterial Viability Kit. These findings indicate that most lichenized fungal and algal cells can survive in space after full exposure to massive UV and cosmic radiation, conditions proven to be lethal to bacteria and other microorganisms. The lichen upper cortex seems to provide adequate protection against solar radiation. Moreover, after extreme dehydration induced by high vacuum, the lichens proved to be able to recover, in full, their metabolic activity within 24 hours.


Decomposition treatment of SO2F2 using packed bed DBD plasma followed by chemical absorption.
The technology of packed bed dielectric barrier discharge (DBD) plasma followed by a chemical absorption has been developed and was found to be an efficient way for decomposition treatment of sulfuryl fluoride (SO2F2) in simulated residual fumigant. The effects of energy density, initial SO2F2 concentration, and residence time on the removal efficiency of SO2F2 for the DBD plasma treatment alone were investigated. It was found that the SO2F2 could be removed completely when initial volume concentration, energy density, and residence time were 0.5%, 33.9 kJ/L, and 5.1 s, respectively. The removal mechanism of SO2F2 in the packed bed DBD reactor was discussed. Based on the detailed analysis of SO2F2 molecular stability and its exhaust products in the DBD plasma reactor, it was concluded that the energetic electrons generated in the packed bed DBD reactor played a key role on the removal of SO2F2, and the major decomposition products of SO2F2 detected were SO2, SiF4, and S (Sulfur). Among these products, SiF4 was formed by the F atom reacted with the filler-quartz glass beads (SiO2) in the packed bed DBD reactor. Aqueous NaOH solution was used as the chemical absorbent for the gaseous products of SO2F2 after plasma pretreatment. It was found that the gaseous products in the plasma exhaust could be absorbed and fixed by the subsequent aqueous NaOH solution.


A nurse clinician's role in the management of hypertension.
The nurse has assumed more responsibility for patients with hypertension, not only in their education, but also in their follow-up. In this study the physician was aware of each patient's progress through conference with the nurse clinician. In addition, the nurse clinician consulted the physician about any problems or questions that arose. The nurse also served an educational role by informing patients about their disease and the side effects of the medications being used in their therapy. Since the physician was aware of the progress of these patients, his time was freed for other purposes. The nurse clinician's role in the management of hypertension was beneficial not only to the patient, but also to the physician.


Occurrence and effects of plastic additives on marine environments and organisms: A review.
Plastics debris, especially microplastics, have been found worldwide in all marine compartments. Much research has been carried out on adsorbed pollutants on plastic pieces and hydrophobic organic compounds (HOC) associated with microplastics. However, only a few studies have focused on plastic additives. These chemicals are incorporated into plastics from which they can leach out as most of them are not chemically bound. As a consequence of plastic accumulation and fragmentation in oceans, plastic additives could represent an increasing ecotoxicological risk for marine organisms. The present work reviewed the main class of plastic additives identified in the literature, their occurrence in the marine environment, as well as their effects on and transfers to marine organisms. This work identified polybrominated diphenyl ethers (PBDE), phthalates, nonylphenols (NP), bisphenol A (BPA) and antioxidants as the most common plastic additives found in marine environments. Moreover, transfer of these plastic additives to marine organisms has been demonstrated both in laboratory and field studies. Upcoming research focusing on the toxicity of microplastics should include these plastic additives as potential hazards for marine organisms, and a greater focus on the transport and fate of plastic additives is now required considering that these chemicals may easily leach out from plastics.


New crops for arid lands.
Five plants are described that could be grown commercially under arid conditions. Once the most valuable component has been obtained from each plant (rubber from guayule; seed oil from jojoba, buffalo gourd, and bladderpod; and resin from gumweed), the remaining material holds potential for useful products as well as fuel. It is difficult to realize the full potential of arid land plants, however, because of the complexities of developing the necessary agricultural and industrial infrastructure simultaneously. To do so, multicompany efforts or cooperative efforts between government and the private sector will be required.


A Novel Fracture Prediction Model Using Machine Learning in a Community-Based Cohort.
The prediction of fracture risk in osteoporotic patients has been a topic of interest for decades, and models have been developed for the accurate prediction of fracture, including the fracture risk assessment tool (FRAX). As machine-learning methodologies have recently emerged as a potential model for medical prediction tools, we aimed to develop a novel fracture prediction model using machine-learning methods in a prospective community-based cohort. In this study, 2227 participants (1257 females) with a baseline bone mineral density (BMD) and trabecular bone score were enrolled from the Ansung cohort. The primary endpoint was the fragility fractures reported by patients or confirmed by X-rays. We used 3 different models: CatBoost, support vector machine (SVM), and logistic regression. During a mean 7.5-year follow-up (range, 2.5 to 10 years), fragility fractures occurred in 537 (25.6%) of participants. In predicting total fragility fractures, the area under the curve (AUC) values of the CatBoost, SVM, and logistic regression models were 0.688, 0.500, and 0.614, respectively. The AUC value of CatBoost was significantly better than that of FRAX (0.663; p < 0.001), whereas the the SVM and logistic regression models were not. Compared with the conventional models such as SVM and logistic regression, the CatBoost model had the best performance in predicting total fragility fractures (p < 0.001). According to feature importance in the CatBoost model, the top predicting factors (listed in order) were total hip, lumbar spine, and femur neck BMD, subjective arthralgia score, serum creatinine, and homocysteine. The latter three factors were listed higher than conventional predictors such as age or previous fracture history. In summary, we hereby report the development of a prediction model for fragility fractures using a machine-learning method, CatBoost, which outperforms the FRAX model as well as two conventional machine-learning models. The model was also able to propose novel high-ranking predictors. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.


Antitrypanosomal screening and cytotoxic effects of selected medicinal plants.
Trypanosoma evansi, the causative agent of "surra", infects many species of wild and domestic animals worldwide. In the current study, the aqueous and ethanolic extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and Strobilanthes crispus were screened in vitro for activity against T. evansi. The cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero) cells using MTT-cell proliferation assay. The median inhibitory concentrations (IC50) of the extracts ranged between 2.30 and 800.97 μg/ml and the median cytotoxic concentrations (CC50) ranged between 29.10 μg/ml and 14.53 mg/ml. The aqueous extract of G. hombroniana exhibited the highest selectivity index (SI) value of 616.36, followed by A. malaccensis aqueous extract (47.38). Phytochemical screening of the G. hombroniana aqueous extract revealed the presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here that the aqueous extract of G. hombroniana has potential antitrypanosomal activity with a high SI, and may be considered as a potential source for the development of new antitrypanosomal compounds.


Salvage living donor liver transplantation for posthepatectomy recurrence: a higher incidence of recurrence but promising strategy for long-term survival.
The scarcity of deceased donor organ donation has led to increasing utilization of living donor liver transplantation (LDLT), which is an optimal treatment for cirrhosis associated with hepatocellular carcinoma (HCC). The study thus aims to analyze prognostic factors and beneficial effects of LDLT for patients with HCC. All patients who underwent LDLT for HCC were included in this study. A multivariate analysis of patients' clinicopathologic parameters was performed to determine prognostic factors. Subsequently, the type of LDLT was further analyzed and compared based on the result of multivariate analysis. Overall, 36 (11.9%) of 303 patients were identified as having HCC recurrence after LDLT. Salvage LDLT (sLDLT) defined by liver transplantation for those patients with recurrent HCC after primary liver resection (LR) was identified as the major prognostic factor of HCC recurrence following the transplantation (HR=2.49 [1.12-5.54], p=0.025). The HCC recurrence incidence and recurrence-free survival after LDLT were significantly inferior in the salvage group than the other group. The pre-transplantation factors were further evaluated and resulted in only maximum tumour size ≥5 cm at primary LR(HR=10.79 [2.10-55.43], p=0.004) affecting post-transplantation HCC recurrence in those patients who had been performed sLDLT. However, patients receiving salvage LDLT had 5- and 10-year overall survival of 86.7% and 52.9%, respectively, measured from the time of initial HCC diagnosis. Overall, LDLT achieves a satisfactory result with low incidence of HCC recurrence based on certain transplantation criteria. Despite the higher incidence of HCC recurrence after sLDLT, it remains a promising strategy to improve long-term outcomes.


GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury via upregulating LAS1 expression.
This study aims at investigating whether GAS5 (grow arrest-specific 5) could promote cardiomyocyte apoptosis by upregulating LAS1 expression, thereby participating in the development of myocardial ischemia-reperfusion injury. The expression level of GAS5 in H9c2 cells after hypoxia/reoxygenation (H/R) treatment was detected by quantitative Real time-polymerase chain reaction (qRT-PCR). Myocardial injury markers in H9c2 cells were evaluated using relative commercial kits, including activities of LDH (lactate dehydrogenase), MDA (malondialdehyde), SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The protein expressions of apoptosis-related genes and p38/MAPK pathway-related genes were detected by Western blot. The regulatory effects of GAS5 on the p38/MAPK pathway were assessed after treatment with p38/MAPK pathway inhibitor in H9c2 cells. QRT-PCR results showed that the expression levels of GAS5 and LAS1 in H/R-treated H9c2 cells were remarkably upregulated compared to those of controls. GAS5 overexpression increased activities of LDH, MDA, SOD and GSH-PX in H/R-treated H9c2 cells. Meanwhile, GAS5 overexpression reduced cell proliferation and apoptosis of H/R-treated cells. Western blot results suggested that the pro-apoptosis genes Bax and cytochrome C were upregulated, whereas the anti-apoptosis gene Bcl-2 was downregulated after GAS5 overexpression. The overexpression of LAS1 in H9c2 cells obtained the same results as GAS5 overexpression. Furthermore, the expressions of p-p38 and p-ERK were upregulated by GAS5 overexpression. SB203580, the p38/MAPK pathway inhibitor, could reverse the inhibited proliferation and increase apoptosis induced by overexpression of GAS5. GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury by upregulating LAS1 expression via p38/MAPK pathway. GAS5 may be a potential therapeutic target for myocardial ischemia-reperfusion injury.


The proactive brain: memory for predictions.
It is proposed that the human brain is proactive in that it continuously generates predictions that anticipate the relevant future. In this proposal, analogies are derived from elementary information that is extracted rapidly from the input, to link that input with the representations that exist in memory. Finding an analogical link results in the generation of focused predictions via associative activation of representations that are relevant to this analogy, in the given context. Predictions in complex circumstances, such as social interactions, combine multiple analogies. Such predictions need not be created afresh in new situations, but rather rely on existing scripts in memory, which are the result of real as well as of previously imagined experiences. This cognitive neuroscience framework provides a new hypothesis with which to consider the purpose of memory, and can help explain a variety of phenomena, ranging from recognition to first impressions, and from the brain's 'default mode' to a host of mental disorders.


Is affect aversive to young children with autism? Behavioral and cardiac responses to experimenter distress.
The aim of this study was to determine whether displays of negative emotions are more aversive to young children with autism than displays of neutral emotions. The attention, behavioral reactions, facial affect, and cardiac responses of 22 autistic and 22 mentally retarded 3-5-year-old children were compared when an experimenter pretended to hurt herself and showed strong distress in contrast to when the experimenter pretended to hurt herself but showed only neutral affect. The children in both diagnostic groups looked more at the experimenter and appeared more interested and concerned when she displayed strong distress than when she showed neutral affect. The heart rate of the mentally retarded children decreased during the distress condition relative to a baseline condition, but the heart rate of the children with autism did not change across conditions. In summary, the children with autism gave no evidence of being overly aroused by or avoiding the distressed experimenter.


Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis.
Fenretinide is a synthetic retinoid pharmaceutical linked to ceramide build-up in vivo. Saposin D is an intralysosomal protein necessary for ceramide binding/degradation. We show, via electronic absorption spectroscopy, fluorescence spectroscopy, and ceramide hydrolysis assays, that fenretinide is bound by saposin D {K a = (1.45 ± 0.49) × 105 M-1}, and affects ceramide solubilization/degradation.


Current trends and problems in health screening.
Automation in clinical chemistry is a powerful tool. Like most innovations it is posing many questions as well as resolving some. Its use in population screening has led to questioning the validity of the old system of ;normal values' and to the search for better methods of indicating the significance of laboratory tests. This in itself is likely to have a good effect in that it is leading to a rigorous examination of the clinical value in diagnosis of the ever increasing number of laboratory tests.The ease and cheapness with which laboratory screening can be carried out is in itself a danger; it can readily lead to an increasingly large diagnostic effort but diminishing returns, including some inconvenience or even harm to a fair proportion of the people screened. It is, therefore, important to examine thoroughly, through population surveys and intervention studies, the validity of all novel forms of prescriptive screening, including those of clinical chemistry. Cheapness of testing needs to be examined in the wider context of the overall cost-effectiveness of screening.


A phase II trial of high dose carboplatin and paclitaxel with G-CSF and peripheral blood stem cell support followed by surgery and/or chest radiation in patients with stage III non-small cell lung cancer: CALGB 9531.
We designed a phase II trial to evaluate the efficacy and tolerability of high dose induction chemotherapy with carboplatin and paclitaxel with G-CSF and stem cell support followed by surgical resection and/or chest radiotherapy in patients with stage III non-small cell lung cancer (NSCLC). Patients had pathologically confirmed stage IIIA-IIIB NSCLC, adequate end-organ function, no prior chemotherapy or radiation, and performance status 0-1. Peripheral stem cells were mobilized with G-CSF stimulation on days 1-5 and collected prior to chemotherapy. Chemotherapy consisted of 2 cycles of paclitaxel 250 mg/m(2) over 3h and carboplatin at an AUC 18 on days 11 and 32, each followed by stem cell reinfusion. Stable and responding patients went on to surgical resection (in patients deemed resectable) followed by post-operative radiation, or to conventional chest radiotherapy to 66 Gy in unresectable patients. Twelve patients (11 eligible) were accrued from 1996 to 1999. The 11 patients were predominately male (64%), white (82%), of performance status 0 (64%), and with weight loss less than 5% (55%). The median age was 51 (range 31-63). Ten (10) patients (91%) experienced grade 4 toxicity. There were no lethal toxicities. Grade 3-4 toxicities most commonly reported included: platelets (100%), lymphocytopenia (91%), leukopenia (91%), neutropenia (73%), anemia (55%), pain (45%), and nausea (27%). Three patients (27%) had a partial response to induction chemotherapy. Of the 11 patients, 7 underwent surgical exploration, and 10 received radiation. Two patients were completely resected, 3 patients had incomplete resections, and 2 patients had no resection. There were 4 complete responses and 3 partial responses following surgery and/or radiation. The median overall survival time was 17.8 months. The median failure-free survival time was 8.3 months. One-year and 2-year overall survival are estimated at 64% and 27%, respectively. High dose induction chemotherapy with carboplatin and paclitaxel and stem cell support in patients with stage IIIA-IIIB NSCLC produced response rates and survival similar to standard therapy. Excessive toxicity (and cost) suggests that this approach does not merit further investigation.


CDE Perspectives of Providing New-Onset Type 1 Diabetes Education Using Formal Vignettes and Simulation.
Purpose The purpose of this article is to describe the 4 Parent Education Through Simulation-Diabetes (PETS-D) nurse certified diabetes educators' (CDEs) perspectives of teaching parents of children with newly diagnosed type 1 diabetes mellitus (T1DM) early diabetes management skills using formal vignettes and a human patient simulator/human patient simulation (HPS) to augment/enhance the teaching-learning process. Methods A qualitative descriptive approach was used. Four CDEs were interviewed by phone about their teaching experiences. Meticulous notes were taken. Data were analyzed using qualitative content analysis. Results The vignettes (and use of HPS) provided structure, especially for parents who were struggling to learn. Certified diabetes educators described a short learning curve to master the use of the HPS manikin. Human patient simulation-enhanced education was described as helpful for teaching multiple caregivers about diabetes. Certified diabetes educators also described factors that affect parent learning, mechanical issues with the HPS, and additional space requirements for HPS-enhanced education. Conclusion Vignettes and HPS-enhanced education can successfully be used to educate parents of children with new-onset T1DM and were preferred by the CDEs when compared with previous teaching strategies. The results of this study support the use of both vignette-based and HPS-enhanced education when a child is newly diagnosed with T1DM. Further studies need to be done to see if these effects persist with different populations, during different stages of the disease, and for individuals with other chronic illnesses.


Activation of the habenula complex evokes autonomic physiological responses similar to those associated with emotional stress.
Neurons in the lateral habenula (LHb) discharge when an animal anticipates an aversive outcome or when an expected reward is not forthcoming, contributing to the behavioral response to aversive situations. So far, there is little information as to whether the LHb also contributes to autonomic physiological responses, including increases in body temperature (emotional hyperthermia) that are integrated with defensive behaviors. Vasoconstriction in cutaneous vascular bed and heat production in brown adipose tissue (BAT) both contribute to emotional hyperthermia. Our present study determines whether stimulation of the LHb elicits constriction of the tail artery and BAT thermogenesis in anesthetized Sprague-Dawley rats. Disinhibition of neurons in LHb with focal microinjections of bicuculline (1 nmol in 100 nl, bilaterally) acutely increased BAT temperature (+0.6 ± 0.1°C, n = 9 rats, P < 0.01) and reduced tail artery blood flow (by 88 ± 4%, n = 9 rats, P < 0.01). Falls in mesenteric blood flow, simultaneously recorded, were much less intense. The pattern of BAT thermogenesis and cutaneous vasoconstriction elicited by stimulating the habenula is similar to the pattern observed during stress-induced emotional hyperthermia, suggesting that the habenula may be important in this response.


Botulinum toxin in treating spasticity.
The value of locally injected botulinum toxin is emphasised. The toxin was injected directly into the skeletal muscles of eight patients with severe spasticity due to stroke-related hemiplegia. It produced both subjective and objective improvement. The toxin injections were well tolerated and no significant side effects were noted.


[Significance of bovine herpesvirus 4 and its detection].
In the last years different strains of the bovine cytomegalo-virus have been isolated. They have been grouped as bovine herpes virus 4 (BHV 4) and separated from other bovine herpes viruses. Their clinical importance remains uncertain. Different tests to detect infection have been developed.


Immunity and leg ulcers in homozygous sickle cell disease.
Probably because of an abnormality of the alternative pathway of complement activation, acute bacterial infections are common in patients with homozygous sickle cell (SS) disease. To find out whether defective immunity might also predispose to chronic bacterial infection, SS patients with indolent ulcers of the legs were studied. When compared with SS individuals who had never had ulcers the differences of serum immunoglobulin and complement component concentration were similar to those found in a comparison of ulcer patients with normal (AA) haemoglobin genotype and AA controls. Both ulcer groups had higher than normal prevalences of serum cryoprecipitates and anticomplementary activity. However, the latter was found less commonly in SS patients than AA patients, suggesting that SS patients form immune complexes which lack the ability to fix complement. They may therefore have a defect of immune elimination which could predispose to chronicity of infection even in the presence of an adequate antibody response.


Light and electron microscope analysis of lectin binding to adult rat liver in situ.
A comprehensive mapping of lectin receptors on adult rat liver in situ was performed at light and ultrastructural levels by using 12 biotin-labeled lectins and an avidin-biotin-peroxidase complex. In addition, concanavalin A conjugated directly to peroxidase was utilized to study intracellular membrane glycoconjugates. To achieve optimal preservation of these membrane sugar moieties, several fixatives and fixation procedures were evaluated. A periodate-lysin-paraformaldehyde combination provided the best compromise between preservation of ultrastructural details and lectin-binding reactivity. Hepatocyte cell surfaces reacted intensely with concanavalin A, Lens culinaris agglutinin, and Pisum sativum agglutinin (all specific for alpha-D-mannosyl and alpha-D-glucosyl groups) as well as Ricinus communis agglutinin type I (specific for alpha or beta-D-galactose) and wheat germ agglutinin (specific for neuraminic acid and beta-NAc-glucosaminyl groups). In addition, R. communis agglutinin and wheat germ agglutinin exhibited an extremely strong reactivity for bile canaliculi which surpassed the binding of concanavalin A, L. culinaris agglutinin, and P. sativum to these structures. Phaseolus vulgaris agglutinin (specific for beta-D-galactose-glucosyl-NAc and D-mannosyl groups), which exhibited a moderate binding to hepatocyte plasma membranes, reacted more strongly with the endothelium of sinusoids and portal vessels. Although all six of these lectins plus Bandeiraea simplicifolia stained Kupffer cells, B. simplicifolia lectin (an alpha-D-galactosyl marker) was unique in showing a strong reactivity for only this cell type. The avidin-biotin-peroxidase procedure is a sensitive method for detection of sugar moieties on cell surfaces of rat liver at both light and electron microscopic levels. In this study, the procedure was used to localize differential binding of lectins to several anatomical structures of the organ, and furthermore, we were able to map preferential localizations of carbohydrate residues in the glycocalyx of the rat hepatocyte in situ.


Cross reactivity between Anaplasma marginale and two Plasmodium species as demonstrated by passive hemagglutination.
Two types of antigens were prepared from each of 3 partially purified preparations of Anaplasma marginale, Plasmodium lophurae, and P berghei. Hemagglutination tests were conducted with homologous serums to detect antigenic relationships between these organisms. Serums were also absorbed with both homologous and heterologous antigen preparations. Cross reactivity between these organisms was observed.


Diversity and evolution of myxozoan minicollagens and nematogalectins.
Myxozoa are a diverse group of metazoan parasites with a very simple organization, which has for decades eluded their evolutionary origin. Their most prominent and characteristic feature is the polar capsule: a complex intracellular structure of the myxozoan spore, which plays a role in host infection. Striking morphological similarities have been found between myxozoan polar capsules and nematocysts, the stinging structures of cnidarians (corals, sea anemones and jellyfish) leading to the suggestion that Myxozoa and Cnidaria share a more recent common ancestry. This hypothesis has recently been supported by phylogenomic evidence and by the identification of a nematocyst specific minicollagen gene in the myxozoan Tetracapsuloides bryosalmonae. Here we searched genomes and transcriptomes of several myxozoan taxa for the presence of additional cnidarian specific genes and characterized these genes within a phylogenetic context. Illumina assemblies of transcriptome or genome data of three myxozoan species (Enteromyxum leei, Kudoa iwatai, and Sphaeromyxa zaharoni) and of the enigmatic cnidarian parasite Polypodium hydriforme (Polypodiozoa) were mined using tBlastn searches with nematocyst-specific proteins as queries. Several orthologs of nematogalectins and minicollagens were identified. Our phylogenetic analyses indicate that myxozoans possess three distinct minicollagens. We found that the cnidarian repertoire of nematogalectins is more complex than previously thought and we identified additional members of the nematogalectin family. Cnidarians were found to possess four nematogalectin/ nematogalectin-related genes, while in myxozoans only three genes could be identified. Our results demonstrate that myxozoans possess a diverse array of genes that are taxonomically restricted to Cnidaria. Characterization of these genes provide compelling evidence that polar capsules and nematocysts are homologous structures and that myxozoans are highly degenerate cnidarians. The diversity of minicollagens was higher than previously thought, with the presence of three minicollagen genes in myxozoans. Our phylogenetic results suggest that the different myxozoan sequences are the results of ancient divergences within Cnidaria and not of recent specializations of the polar capsule. For both minicollagen and nematogalectin, our results show that myxozoans possess less gene copies than their cnidarian counter parts, suggesting that the polar capsule gene repertoire was simplified with their reduced body plan.


Cartilage oligomeric matrix protein (COMP) promotes cell proliferation in early-onset colon cancer tumorigenesis.
Colon cancer (CC) is the third most commonly diagnosed cancer in the USA. While the overall incidence is declining, it is rising alarmingly in young patients (EOCC). CC in young patients tends to be more aggressive and often diagnosed at more advanced stages and portend poorer prognosis. Our recently published data showed that EOCC is a distinct disease with unique molecular features compared to late-onset CC (LOCC). The Cartilage Oligomeric Matrix Protein (COMP) was shown to be significantly upregulated in EOCC and correlated with poor survival. However, the role of COMP in CC tumorigenesis, especially in young patients, is not well understood. Thus, the aim of this study was to elucidate the role of COMP in CC tumorigenesis by modulating COMP levels in vitro and test how it affects proliferation. Then, patient samples were evaluated by testing the levels of proliferation marker Ki67. In addition, this study investigates whether higher transcriptional mRNA levels of COMP seen in more aggressive early-onset CC correlate with protein levels compared to late-onset CC. COMP mRNA levels in fresh frozen colon tumors (young: n = 5; old: n = 5) were assessed by quantitative PCR (qPCR). Additionally, CC cell lines were profiled for COMP expression to choose an in vitro model to study the role of COMP in CC tumorigenesis. HT-29 (low COMP expression) and CaCo-2 (high COMP expression) cells were used for in vitro proliferation studies. Immunohistochemical (IHC) analysis was conducted to assess COMP and Ki67 protein levels in formalin-fixed paraffin-embedded (FFPE) colon tumors. Significantly higher COMP expression levels were observed in fresh frozen EOCC compared to LOCC tumors. This observation confirmed our previously reported results from NanoString gene expression assay using FFPE samples. Cell proliferation was significantly increased in HT-29 and CaCo-2 cells upon treatment with human recombinant COMP protein after 48 and 72 h (P < 0.05). This increase was more profound in HT-29 cells. Staining for COMP and Ki67 revealed high COMP protein levels in EOCC compared to LOCC patients. COMP mRNA and protein levels are significantly higher in EOCC patients. Higher COMP levels correlate with increased proliferation suggesting a role in CC tumorigenesis.


Human alpha-defensin-1 inhibits growth of human lung adenocarcinoma xenograft in nude mice.
Human alpha-defensin-1 (HNP1), a small antimicrobial peptide, shows cytotoxicity to tumor cells in vitro and inhibitory activity for pathologic neovascularization in vivo. Here, we did a gene therapy with a plasmid that expresses a secretable form of HNP1 for assaying its antitumor activity. The expression and secretion of HNP1 were determined by reverse transcription-PCR and ELISA in vitro. We found that expression of HNP1 in A549 tumor cells caused significant growth inhibition. This effect is most likely cell autonomous, as a significant amount of recombinant HNP1 protein was found to be accumulated in the cytoplasm by immunohistochemical staining using an anti-HNP1 antibody and the supernatant containing secreted HNP1 failed to produce any noticeable antitumor activity. Flow cytometry and Hoechst 33258 staining showed that the number of apoptotic cells among the A549 cells expressing recombinant HNP1 proteins was significantly greater than that of the nontransfected control cultures, suggesting that this growth-inhibitory activity was due to an apoptotic mechanism triggered by the intracellular HNP1. The antitumor activity of intracellularly expressed HNP1 was also shown in vivo. Decreased microvessel density and increased lymphocyte infiltration were observed in tumor tissue from HNP1-treated mice through histologic analysis. These results indicate that intracellularly expressed HNP1 induces tumor cell apoptosis, which inhibits tumor growth. The antiangiogenesis effect of HNP1 may contribute to its inhibitory activity in vivo, and HNP1 might involve the host immune response to tumor. These findings provide a rationale for developing HNP1-based gene therapy for cancer.


Neurosyphilis.
In patients with abnormal neuropsychiatric symptoms and a reactive fluorescent treponemal antibody absoption (FTA-ABS) test in the cerebrospinal fluid (CSF) or serum, a normal CSF cell count and total protein concentration does not exlude late syphilis involving the central nervous system. In these patients, the presence of plasma cells in the CSF cytogram, increased concentration of CSF immunoglobulin G (IgG), immunoelectrophoretic abnormalities in the precipitates of the IgG and of the Fab fragments of IgG in the CSF immunoelectropherogram, and an increased serum level of immunoglobulin M (IgM) suggest an active, potentially treatable neurosyphilis.


Evolution. Comment on "A promiscuous intermediate underlies the evolution of LEAFY DNA binding specificity".
Sayou et al. (Reports, 7 February 2014, p. 645) proposed a new model for evolution of transcription factors without gene duplication, using LEAFY as an archetype. Their proposal contradicts the evolutionary history of plants and ignores evidence that LEAFY evolves through gene duplications. Within their data set, we identified a moss with multiple LEAFY orthologs, which contests their model and supports that LEAFY evolves through duplications.


Computational design of a thermostable mutant of cocaine esterase via molecular dynamics simulations.
Cocaine esterase (CocE) has been known as the most efficient native enzyme for metabolizing naturally occurring cocaine. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only ∼11 min at physiological temperature (37 °C). It is highly desirable to develop a thermostable mutant of CocE for therapeutic treatment of cocaine overdose and addiction. To establish a structure-thermostability relationship, we carried out molecular dynamics (MD) simulations at 400 K on wild-type CocE and previously known thermostable mutants, demonstrating that the thermostability of the active form of the enzyme correlates with the fluctuation (characterized as the root-mean square deviation and root-mean square fluctuation of atomic positions) of the catalytic residues (Y44, S117, Y118, H287, and D259) in the simulated enzyme. In light of the structure-thermostability correlation, further computational modelling including MD simulations at 400 K predicted that the active site structure of the L169K mutant should be more thermostable. The prediction has been confirmed by wet experimental tests showing that the active form of the L169K mutant had a half-life of 570 min at 37 °C, which is significantly longer than those of the wild-type and previously known thermostable mutants. The encouraging outcome suggests that the high-temperature MD simulations and the structure-thermostability relationship may be considered as a valuable tool for the computational design of thermostable mutants of an enzyme.


Interpretation of digital mammograms: comparison of speed and accuracy of soft-copy versus printed-film display.
To compare the speed and accuracy of the interpretations of digital mammograms by radiologists by using printed-film versus soft-copy display. After being trained in interpretation of digital mammograms, eight radiologists interpreted 63 digital mammograms, all with old studies for comparison. All studies were interpreted by all readers in soft-copy and printed-film display, with interpretations of images in the same cases at least 1 month apart. Mammograms were interpreted in cases that included six biopsy-proved cancers and 20 biopsy-proved benign lesions, 20 cases of probably benign findings in patients who underwent 6-month follow-up, and 17 cases without apparent findings. Area under the receiver operating characteristic curve (A(z)), sensitivity, and specificity were calculated for soft-copy and printed-film display. There was no significant difference in the speed of interpretation, but interpretations with soft-copy display were slightly faster. The differences in A(z), sensitivity, and specificity were not significantly different; A(z) and sensitivity were slightly better for interpretations with printed film, and specificity was slightly better for interpretations with soft copy. Interpretation with soft-copy display is likely to be useful with digital mammography and is unlikely to significantly change accuracy or speed.


Long-term care and hospital utilisation by older people: an analysis of substitution rates.
Older people are intensive users of hospital and long-term care services. This paper explores the extent to which these services are substitutes. A small area analysis was used with both care home and (tariff cost-weighted) hospital utilisation for older people aggregated to electoral wards in England.Health and social-care structural equations were specified using a theoretical model. The estimation accounted for the skewed and censored nature of the data. For health utilisation, both a fixed effects instrumental variables GMM model and a generalised estimating equations (GEE) model were fitted, the later on a log dependent variable with predicted values of social care utilisation used to account for endogeneity (bootstrapping was used to derive standard errors). In addition to a GMM model, the social-care estimation used both two-part and tobit models (also with predicted health utilisation and bootstrapping).The results indicate that for each additional pound1 spent on care homes, hospital expenditure falls by pound0.35. Also, pound1 additional hospital spend corresponds to just over pound0.35 reduction on care home spend. With these cost substitution effects offsetting, a transfer of resources to care homes is efficient if the resultant outcome gain is greater than the outcome loss from reduced hospital use.


Comparison of Emergency Department Visits for Complications of Gastrostomy Versus Gastrojejunostomy Tubes in Children.
This study aims to evaluate frequency, type, and cost of gastrostomy tube (GT) versus gastrojejunostomy tube (GJT) complications in children presenting to the emergency department (ED). Patients were selected by electronic health record search for International Classification of Diseases, Ninth Revision, and procedure codes for GTs and GJTs/jejunostomy tubes. All children aged less than 18 years with GTs or GJTs placed during a 5-year period (2007-2012) at the University of Minnesota Masonic Children's Hospital were identified for retrospective review. Comparisons were made on demographic data, number and type of complications, and interventions performed for ED visits, which were abstracted from the electronic health record. Cost data were abstracted from the financial data system. A total of 161 GT and GJT patients were identified; 31 children had 43 ED visits for complications. Ages ranged from 1 month to 17 years; median, 12 months; mean, 5.4 years; 25 (58%) were male, and 18 female (42%). Complications occurred in 15 GT (48.4%) and 16 GJT (51.6%) patients. The most common ED presenting complication was dislodgement, which occurred in 14 GTs (67%) and 18 GJTs (82%), followed by clogging 6 GTs (29%) and 1 GJTs (4.5%). Those presenting to the ED with GJT complications had higher mean overall charge (US $1987.00 vs US $913.10, P = 0.05). Although GTs and GJTs had similar rates of complications and ED visits, GJT complications were more likely to result in hospital admission and intervention by radiology, require specialist involvement, and have a higher cost charged to the patient.


TTC17 is an endoplasmic reticulum resident TPR-containing adaptor protein.
Protein folding, quality control, maturation, and trafficking are essential processes for proper cellular homeostasis. Around one-third of the human proteome is targeted to the endoplasmic reticulum (ER), the organelle that serves as entrance into the secretory pathway. Successful protein trafficking is paramount for proper cellular function and to that end there are many ER resident proteins that ensure efficient secretion. Here, biochemical and cell biological analysis was used to determine that TTC17 is a large, soluble, ER-localized protein that plays an important role in secretory trafficking. Transcriptional analysis identified the predominantly expressed protein isoform of TTC17 in various cell lines. Further, TTC17 localizes to the ER and interacts with a wide variety of chaperones and cochaperones normally associated with ER protein folding, quality control, and maturation processes. TTC17 was found to be significantly upregulated by ER stress and through the creation and use of TTC17-/- cell lines, quantitative mass spectrometry identified secretory pathway wide trafficking defects in the absence of TTC17. Notably, trafficking of insulin-like growth factor type 1 receptor, glycoprotein nonmetastatic melanoma protein B, clusterin, and UDP-glucose:glycoprotein glucosyltransferase 1 were significantly altered in H4 neuroglioma cells. This study defines a novel ER trafficking factor and provides insight into the protein-protein assisted trafficking in the early secretory pathway.


Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes. PURSUIT Investigators.
We aimed to evaluate the benefits of the glycoprotein (GP) IIb/IIIa antagonist, eptifibatide, after patients with acute coronary syndromes (ACS) were admitted to hospitals that approach revascularization for ACS through early transfer to tertiary referral centers. Across a variety of hospital settings, GP IIb/IIIa inhibition, after patients were admitted to the hospital for non-ST segment elevation ACS, is associated with a reduction in death or myocardial infarction (MI) before and during a percutaneous coronary intervention. The outcomes of 429 patients from 153 sites in the Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, who were transferred during study drug infusion ("transfer patients"), were compared with those of 1,987 patients who either remained in the hospital at those sites or were transferred after study drug termination ("nontransfer patients"). The baseline characteristics of transfer and nontransfer patients were similar. Patients receiving eptifibatide were transferred less frequently than those receiving placebo (16% vs. 20%, p = 0.014). Transfer patients underwent more procedures and experienced a greater 30-day incidence of death or MI, as compared with nontransfer patients (21% vs. 12%, p = 0.001). Eptifibatide was associated with a reduction in death or MI through 30 days, independent of transfer status (2.5% absolute reduction), as well as for those transferred (5.5% absolute reduction). For patients with ACS admitted to community hospitals, eptifibatide is associated with a reduced need for transfer and improved clinical outcomes.


A Framework to Improve Energy Efficient Behaviour at Home through Activity and Context Monitoring.
Real-time Localization Systems have been postulated as one of the most appropriated technologies for the development of applications that provide customized services. These systems provide us with the ability to locate and trace users and, among other features, they help identify behavioural patterns and habits. Moreover, the implementation of policies that will foster energy saving in homes is a complex task that involves the use of this type of systems. Although there are multiple proposals in this area, the implementation of frameworks that combine technologies and use Social Computing to influence user behaviour have not yet reached any significant savings in terms of energy. In this work, the CAFCLA framework (Context-Aware Framework for Collaborative Learning Applications) is used to develop a recommendation system for home users. The proposed system integrates a Real-Time Localization System and Wireless Sensor Networks, making it possible to develop applications that work under the umbrella of Social Computing. The implementation of an experimental use case aided efficient energy use, achieving savings of 17%. Moreover, the conducted case study pointed to the possibility of attaining good energy consumption habits in the long term. This can be done thanks to the system's real time and historical localization, tracking and contextual data, based on which customized recommendations are generated.


Effects of the probiotic formulation SLAB51 in in vitro and in vivo Parkinson's disease models.
Parkinson is a common neurodegenerative disorder, characterized by motor and non-motor symptoms, including abnormalities in the gut function, which may appear before the motor sign. To date, there are treatments that can help relieve Parkinson' disease (PD)-associated symptoms, but there is no cure to control the onset and progression of this disorder. Altered components of the gut could represent a key role in gut-brain axis, which is a bidirectional system between the central nervous system and the enteric nervous system. Diet can alter the microbiota composition, affecting gut-brain axis function. Gut microbiome restoration through selected probiotics' administration has been reported. In this study, we investigated the effects of the novel formulation SLAB51 in PD. Our findings indicate that this probiotic formulation can counteract the detrimental effect of 6-OHDA in vitro and in vivo models of PD. The results suggest that SLAB51 can be a promising candidate for the prevention or as coadjuvant treatment of PD.


Cardiac Magnetic Resonance for Evaluating Nonculprit Lesions After Myocardial Infarction: Comparison With Fractional Flow Reserve.
This study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis. The agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown. Seventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ≤0.80. Hemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%. CMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.


Health care reform's effect on home care: strategies for survival.
Home care is expected to thrive under President Clinton's health care reform proposal, growing from a $12.1 billion business in 1995 to $18.8 billion by the year 2000. While the home care industry grows, both public and private payers will be increasing their interest in reviewing home care services provided and billed. Home care companies must prepare for a future that includes increased interaction with managed care plans. In this article, the authors discuss strategies for home care providers to succeed in a managed care environment.


[Condition of the nervous elements of skeletal muscle in Duchenne myopathy].
In order to determine the role of the nervous system in the pathogenesis of myopathy, the author examined the nervous apparatus in a bioptate of the widest muscle of the back in 8 patients with Duchenne's myopathy and in some other muscles in one post-mortem case of the same disease. The morphological changes in the nervous structures of skeletal muscles were expressed in signs of irritation, substituted by destruction which began in the terminal parts and was more expressed in the atrophized muscles. Besides there were symptoms of excessive growth of the nervous filaments especially in the initial phases of the process. The regenerating nervous filaments are subjected to destruction and do not provide an innervation of the muscles.


Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma.
We have recently performed the characterization of alternative splicing events (ASEs) in head and neck squamous cell carcinoma, which allows dysregulation of protein expression common for cancer cells. Such analysis demonstrated a high ASE prevalence among tumor samples, including tumor-specific alternative splicing in the GSN gene.In vitro studies confirmed that overall expression of either ASE-GSN or wild-type GSN (WT-GSN) isoform inversely correlated with cell proliferation, whereas the high ratio of ASE-GSN to WT-GSN correlated with increased cellular invasion. Additionally, a change in expression of either isoform caused compensatory changes in expression of the other isoform. Our results suggest that the overall expression and the balance between GSN isoforms are mediating factors in proliferation, while increased overall expression of ASE-GSN is specific to cancer tissues. As a result, we propose ASE-GSN can serve not only as a biomarker of disease and disease progression, but also as a neoantigen for head and neck squamous cell carcinoma treatment, for which only a limited number of disease-specific targeted therapies currently exist.