Evaluating the usability of a virtual reality-based Android application in managing the pain experience of wheelchair users.
Pain constitutes an important medical concern that can have severe implications to a wheelchair user's quality of life. Results from studies indicate that pain is a common problem in this group of individuals, having a reported frequency of always (12%) and everyday (33%). This incidence signifies the need for more applicable and effective pain management clinical tools. As a result, in this paper we present an Android application (PainDroid) that has been enhanced with Virtual Reality (VR) technology for the purpose of improving the management of pain. Our evaluation with a group of wheelchair users revealed that PainDroid demonstrated high usability among this population, and is foreseen that it can make an important contribution in research on the assessment and management of pain.


Gas-phase CO2 subtraction for improved measurements of the organic aerosol mass concentration and oxidation degree by an aerosol mass spectrometer.
The Aerodyne aerosol mass spectrometer (AMS) has been widely used for real-time characterization of the size-resolved chemical composition of sub-micrometer aerosol particles. The first step in AMS sampling is the pre-concentration of aerosols while stripping away the gas-phase components, which contributes to the high sensitivity of this instrument. The strength of the instrument lies in particle phase measurement; however, ion signals generated from gas-phase species can influence the interpretation of the particle-phase chemistry data. Here, we present methods for subtracting the varying contributions of gas-phase carbon dioxide (CO2) in the AMS spectra of aerosol particles, which is critical for determining the mass concentration and oxygen-to-carbon (O/C) ratio of organic aerosol. This report gives details on the gaseous CO2 subtraction analysis performed on a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) data set acquired from sampling of fresh and diluted vehicle emissions. Three different methods were used: (1) collocated continuous gas-phase CO2 measurement coupled with periodic filter tests consisting of sampling the same particle-free air by the AMS and the CO2 analyzer, (2) positive matrix factorization (PMF) analysis to separate the gas- and particle-phase signals of CO2(+) at m/z 44, and (3) use of the particle time-of-flight (PTOF) size-resolved chemical information for separation of gas- and particle-phase signals at m/z 44. Our results indicate that these three different approaches yield internally consistent values for the gas/particle apportionment of m/z 44, but methods 2 and 3 require certain conditions to be met to yield reliable results. The methods presented are applicable to any situation where gas-phase components may influence the PM signal of interest.


Characteristics of high-quality guidelines: evaluation of 86 clinical guidelines developed in ten European countries and Canada.
To identify predictors of high-quality clinical practice guidelines. A total of 86 guidelines from 11 countries were assessed by four independent appraisers per guideline using the AGREE instrument (23 items). Six aspects of guideline development were considered to explain the variation in quality scores: care level (primary/secondary care), scope (diagnosis/treatment), type of guideline (new/update), year of publication, type of agency (governmental/professional), and whether the guideline was produced within a structured and coordinated program. Guidelines produced within a guideline program and by governmental agencies had higher scores than their counterparts. Differences in the applicability of the guidelines could not be explained by the variables studied. To ensure high quality, clinical guidelines should be produced within a structured and coordinated program. Professional organizations or specialist societies that aim to develop guidelines may adopt quality criteria from leading guideline agencies.


Reproductive biology of the Green Ground Snake Erythrolamprus poecilogyrus sublineatus (Serpentes: Dipsadidae) in Subtropical Brazil.
We investigated reproductive features of the dipsadid snake Erythrolamprus poecilogyrus sublineatus in the southernmost Brazilian coast, a subtropical region characterized by well-marked seasons. Females are significantly smaller than males, have a shorter tail, and reach sexual maturity at later times along their development. In contrast to tropical subspecies, E. p. sublineatus females presented a seasonal pattern, with secondary follicles occurring from late winter to early autumn and egg production restricted to the whole spring and early summer. Males presented seasonal variation in testes volume (increase in autumn and decrease in winter) while no significant seasonal variation was found in ductus deferens width. The number of oviductal eggs varied from two to nine, thus, real fecundity is also inferior than that observed in tropical E. poecilogyrus forms. Considering the thermal requirements for reproduction, it is possible that the colder climatic conditions of the southern Brazilian coast have shaped the seasonal reproductive pattern in E. p. sublineatus. The shorter body size of this subspecies may also represent a conditioning factor of low fecundity.


Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma.
Angiogenesis is in part related to mast cells. However, the biological significance of mast cells within lung carcinoma remains unclear. Immunohistochemistry was used to stain for tryptase, CD34 and vascular endothelial growth factor (VEGF) in 85 cases of stage I nonsmall cell lung carcinoma. VEGF was found in 33 of 53 adenocarcinomas and 14 of 32 squamous cell carcinomas. Cases of adenocarcinoma had significantly higher mast cell counts than those of squamous cell carcinoma. In adenocarcinoma, mast cell counts in VEGF-positive tumours were significantly higher than in VEGF-negative tumours, whereas in squamous cell carcinoma they were not. Good correlation was observed between intratumoural mast cell counts and microvessel counts. Double staining showed most intratumoural mast cells expressed VEGF. Importantly, only in lung adenocarcinoma, members in the high mast cell count group had significantly worse prognosis than those in the low mast cell count group. It is concluded that tumour-released vascular endothelial growth factors may be related to mast cell accumulation, intratumoural mast cells may produce vascular endothelial growth factor, and stromal mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma.


Changes in calcium distribution during therapeutic plasmapheresis.
Observations of normal persons indicated that there was a net shift of serum calcium from the ionized and protein-bound fractions to the anion-bound fraction when these persons received citrate during donor plasmapheresis. To confirm these findings and to extend them to diseased persons, we measured total, ionized, and ultrafilterable Ca concentrations in 11 patients who were undergoing therapeutic plasmapheresis. Anticoagulation was achieved with anticoagulant citrate dextrose solution. Mean concentrations of total, ionized, and protein-bound Ca decreased, whereas the ultrafilterable and anion-bound fractions increased. Our results suggest that protein-bound Ca may be relatively labile and may help to maintain constant levels of ionized Ca. Also, the observed increase in the anion-bound Ca level with citrate infusion suggests a shift from the protein-bound and ionized Ca fractions to this pool.


Effects of the flaxseed lignans secoisolariciresinol diglucoside and its aglycone on serum and hepatic lipids in hyperlipidaemic rats.
The present study involved a comparative analysis of the effects of purified flaxseed lignans, secoisolariciresinol diglucoside (SDG) and its aglycone metabolite (SECO), in hyperlipidaemic rats. For hypercholesterolaemia, female Wistars (six rats per group) were fed a standard or 1 % cholesterol diet and orally administered 0, 3 or 6 mg SDG/kg or 0, 1.6 or 3.2 mg SECO/kg body weight once daily for 4 weeks. Hypertriacylglycerolaemia was induced in male Sprague-Dawley rats (ten rats per group) by supplementing tap water with 10 % fructose. These rats were orally administered 0, 3 or 6 mg SDG/kg body weight once daily for 2 weeks. Fasting blood samples (12 h) were collected predose and at the end of the dosing period for serum lipid analyses. Rats were killed and livers rapidly excised and sectioned for lipid, mRNA and histological analyses. Chronic administration of equimolar amounts of SDG and SECO caused similar dose-dependent reductions in rate of body-weight gain and in serum total and LDL-cholesterol levels and hepatic lipid accumulation. SDG and SECO failed to alter hepatic gene expression of commonly reported regulatory targets of lipid homeostasis. SDG had no effect on serum TAG, NEFA, phospholipids and rate of weight gain in 10 % fructose-supplemented rats. In conclusion, our data suggest that the lignan component of flaxseed contributes to the hypocholesterolaemic effects of flaxseed consumption observed in humans. Future studies plan to identify the biochemical mechanism(s) through which flaxseed lignans exert their beneficial effects and the lignan form(s) responsible.


The frequency and mutation rate of balanced autosomal rearrangements in man estimated from prenatal genetic studies for advanced maternal age.
The frequencies of balanced chromosome rearrangements were estimated from three series of advanced maternal-age prenatal genetic studies, and were compared to the frequencies that had been estimated from consecutive newborn surveys. In the maternal-age prenatal studies, the frequencies were: Robertsonian translocations, 0.11%; reciprocal translocations, 0.17%; and inversions, 0.12%. The total frequency of balanced rearrangements in the prenatal genetic studies performed with banding (0.40%, or 1 in 250) was twice that in the consecutive newborn surveys performed without banding (0.19%, or 1 in 526). The difference was limited to inversions and reciprocal translocations; the frequency of Robertsonian translocations was similar in the prenatal series and the newborn surveys. Both familial and de novo rearrangements were more common than anticipated. The de novo cases provided a mutation rate estimate of 4.3 per 10,000 gametes per generation (compared with 1.78 to 2.2 per 10,000 gametes in other surveys). These higher estimates may more reliably approximate the true mutation rate and frequencies of balanced rearrangements in the newborn population than do the newborn surveys.


Unusual Cystic Variant of Calcifying Epithelial Odontogenic Tumor.
Calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic neoplasm, which is exclusively epithelial in its tissue of origin. Many cases of CEOTs are associated with impacted tooth and simulate dentigerous cyst radiographically. The histologic features of CEOT are unique; however, among its various histologic subtypes, the cystic variant is a rare and less well-understood entity. Our report elucidates a cystic variant of CEOT in the maxilla of a 16-year-old male that presents clinical and radiologic findings conscientious to dentigerous cyst; but histopathological diagnosis came out to be a gold standard in identifying this rare tumor. This case report describes the clinicopathologic features of this rare entity, highlighting the histomorphological findings along with reviewing other reported cases.


Social support and hostility as predictors of depressive symptoms in cardiac patients one month after hospitalization: a prospective study.
Hospitalization for cardiac disease is associated with an increased risk for depression, which itself confers a poorer prognosis. Few prospective studies have examined the determinants of depression after hospitalization in cardiac patients, and even fewer have examined depression within the weeks after hospital discharge. The present study assessed the prospective relations among perceptions of social support and trait hostility in predicting symptoms of depressive symptoms at 1 month after hospitalization for a diagnostic angiography in 506 coronary artery disease (CAD) patients. A series of structural equation models 1) estimated the predictive relations of social support, hostility, and depressive symptoms while in the hospital to symptoms of depression 1 month after hospitalization, and 2) compared these relations across gender, predicted risk classification, and age. Social support assessed during hospitalization was independently negatively associated with depressive symptoms 1 month after hospitalization, after controlling for baseline symptoms of depression, gender, disease severity, and age. Hostility was an indirect predictor of postdischarge depressive symptomology by way of its negative relation with social support. This pattern of relations did not differ across gender, predicted risk classification, and age. Our findings suggest that a patient's perceived social support during hospitalization is a determinant of depressive symptoms 1 month later. The relation of social support and hostility to subsequent depressive symptoms was similar across a variety of populations.


Phylogeny-based classification of human rhinoviruses detected in hospitalized children with acute lower respiratory infection in Paraguay, 2010-2011.
Human rhinovirus (HRV), a single-stranded, positive-sense RNA virus, is associated with mild upper respiratory tract infections in children. The aim of this study was to carry out a molecular characterization and phylogeny-based classification of the circulating genotypes of HRV in hospitalized children with clinical manifestations of acute lower respiratory infection in Paraguay. Nasopharyngeal aspirates were collected from 101 children under 5 years of age, hospitalized with symptoms of acute lower respiratory infection, between May 2010 and December 2011, at the largest public pediatric hospital in the Central Department of Paraguay. Detection was performed by a real-time polymerase chain reaction, followed by conventional amplification of the VP4/VP2 genomic region, sequencing, and phylogenetic analysis. Rhinovirus was detected in 33.7% of the samples. Amplification of 18 samples showed the presence of all three species (HRV-A, -B, and -C). Different genotypes were found for each species: 11 for HRV-A (-9, -12, -22, -30, -36, -43, -59, -61, -68, -88, and -89), one for HRV-B (-4), and four for HRV-C (-C2, -C3, -C6, and -C9). In South America, information about HRV diversity is scarce. This is the first report on HRV genotype diversity in South America.


Photostable Platinated Bacteriochlorins as Potent Photodynamic Agents.
Photodynamic therapy (PDT) is used to treat various cancerous diseases. Recently, we have demonstrated that platinated pyridyl-substituted porphyrins are potent agents for PDT with very high phototoxicity (IC50 down to 17 nM) and excellent phototoxic indices of higher than 5800 (p.i. = IC50(dark)/IC50(light)) [Rubbiani, R. et al., Chem. Commun. 2020, 56, 14373]. However, the absorption of porphyrins is not ideal for the treatment of larger tumors because they essentially do not absorb light between 650 and 850 nm. Herein, we report stable conjugates of a novel bacteriochlorin with cisplatin and transplatin. They exhibit extremely high phototoxicity (IC50 values down to 6 nM, irradiated with a 750 nm LED at a fluence of 5 J/cm2), very low dark toxicity, and thereby extremely high phototoxic indices up to 8300. Based on these exciting results, we believe that platinated bacteriochlorins are promising candidates for further investigation as novel PDT anticancer agents.


Modulation of sensory perception by hydrogen peroxide enables Caenorhabditis elegans to find a niche that provides both food and protection from hydrogen peroxide.
Hydrogen peroxide (H2O2) is the most common chemical threat that organisms face. Here, we show that H2O2 alters the bacterial food preference of Caenorhabditis elegans, enabling the nematodes to find a safe environment with food. H2O2 induces the nematodes to leave food patches of laboratory and microbiome bacteria when those bacterial communities have insufficient H2O2-degrading capacity. The nematode's behavior is directed by H2O2-sensing neurons that promote escape from H2O2 and by bacteria-sensing neurons that promote attraction to bacteria. However, the input for H2O2-sensing neurons is removed by bacterial H2O2-degrading enzymes and the bacteria-sensing neurons' perception of bacteria is prevented by H2O2. The resulting cross-attenuation provides a general mechanism that ensures the nematode's behavior is faithful to the lethal threat of hydrogen peroxide, increasing the nematode's chances of finding a niche that provides both food and protection from hydrogen peroxide.


A Qualitative Study of the Experiences of Complementary and Alternative Medicine of Patients With IBS-C.
The aim of this study was to examine the complementary and alternative medicine (CAM) experiences of patients with constipation irritable bowel syndrome (IBS-C). This qualitative study consisted of a total of 30 patients, who were admitted to a university hospital in Turkey. Data were collected using a descriptive questionnaire and a semistructured interview. Data analysis identified 5 main themes: (1) constipation-related difficulties experienced due to IBS, (2) the feeling that the CAM use is natural and useful, (3) the effect of the environmental stimuli in preferring the use of CAM, (4) the feeling that CAM is not negative and relieves, and (5) suggesting the CAM use. In conclusion, it was determined that all the patients with constipation IBS used various CAM methods. It may be recommended to raise the awareness of the patients by health care professionals about the CAM methods that may be useful.


Two types of morphologically distinct fibers comprising Gallionella ferruginea twisted stalks.
Two morphologically distinct extracellular stalk fibers produced by Gallionella ferruginea were compared by electron microscopy and elemental analysis. The thick- and fine-fiber stalks were different in structure on a micrometer scale and in the site on the mother cell to which they were attached, but on a nanometer scale they were similar in ultrastructure and in the elemental composition of their basic fiber matrix.


Peering into the 'black box'. Measuring outcomes of managed care.
Research on the impact of managed care on access, quality, outcomes, and costs of mental health and substance abuse services has been limited because of the lack of generalizability of studies, the "black box" focus of much of the research, the dynamic changes in mental health and substance abuse managed care, and the proprietary nature of the health care industry. This article provides a framework for understanding the organizational, financial, and procedural features of health plans and the effect of these features on the characteristics and flow of patients through health plans and the selection and utilization of treatments. The diverse research priorities of key stakeholders, i.e., public and private purchasers, managed care organizations, providers, and patients and their families, are described along with a broader societal agenda for delineating the outcomes of health care plans. Critical research and methodologic issues in studying the effects of managed care are outlined, including issues related to identifying and selecting appropriate outcome measures and developing appropriate methods for risk adjustment to adequately control for patient selection bias. This article asserts that government, purchasers, health care plans, providers, consumers, and researchers must collaboratively develop resources and research approaches to fully evaluate the effects of managed care. To realize this objective, auspices with reasonable objectivity are needed along with access to necessary data within the black box of health care systems, a cadre of trained investigators, and sufficient research funding, including the development of an all payers fund to support clinical and health services research.


Variations and thicknesses of anterior belly of the digastric muscle: an ultrasonographic study.
This study aims to evaluate the anatomy and anatomical variations of the anterior belly of the digastric muscle. Hundred and fifty one ultrasonographic images of the digastric muscle pairs were evaluated in Near East University Faculty of Dentistry Department of Dentomaxillofacial Radiology. Morphological variations were recorded using the classification of the digastric muscle into 12 types by Kim et al. For the analysis, the Mann-Whitney U test and Chi-square test were used, and for the correlational analysis, Spearman's rho test was applied. P < 0.05 was considered statistically significant in all tests. Seventy female and 81 male patients aged 19-60 years were evaluated. Type 1 digastric muscle was observed in 145 of 151 patients, Type 2 in 3 patients, and Type 7 in 3 patients. The thicknesses of the right and left digastric muscles were measured, and a statistically significant difference was observed between the groups when the genders were compared. It was observed that both right and left digastric muscle thicknesses were higher in males than females. There was a statistically significant positive high correlation between right and left digastric muscle thicknesses (p = 0.000; r = 0.736). No statistically significant difference was found between genders (p = 0.596) in terms of anatomical variations. Considering that the variations of the digastric muscle may have a clinical significance role, the normal anatomy and variations of this muscle should be well known by maxillofacial surgeons and radiologists.


Engineering nanostructured polymer blends with controlled nanoparticle location for excellent microwave absorption: a compartmentalized approach.
In order to obtain better materials, control over the precise location of nanoparticles is indispensable. It is shown here that ordered arrangements of nanoparticles, possessing different characteristics (electrical/magnetic dipoles), in the blend structure can result in excellent microwave absorption. This is manifested from a high reflection loss of ca. -67 dB for the best blend structure designed here. To attenuate electromagnetic radiation, the key parameters of high electrical conductivity and large dielectric/magnetic loss are targeted here by including a conductive material [multiwall carbon nanotubes, MWNTs], ferroelectric nanostructured material with associated relaxations in the GHz frequency [barium titanate, BT] and lossy ferromagnetic nanoparticles [nickel ferrite, NF]. In this study, bi-continuous structures were designed using 50/50 (by wt) blends of polycarbonate (PC) and polyvinylidene fluoride (PVDF). The MWNTs were modified using an electron acceptor molecule, a derivative of perylenediimide, which facilitates π-π stacking with the nanotubes and stimulates efficient charge transport in the blends. The nanoscopic materials have specific affinity towards the PVDF phase. Hence, by introducing surface-active groups, an ordered arrangement can be tailored. To accomplish this, both BT and NF were first hydroxylated followed by the introduction of amine-terminal groups on the surface. The latter facilitated nucleophilic substitution reactions with PC and resulted in their precise location. In this study, we have shown for the first time that by a compartmentalized approach, superior EM attenuation can be achieved. For instance, when the nanoparticles were localized exclusively in the PVDF phase or in both the phases, the minimum reflection losses were ca. -18 dB (for the MWNT/BT mixture) and -29 dB (for the MWNT/NF mixture), and the shielding occurred primarily through reflection. Interestingly, by adopting the compartmentalized approach wherein the lossy materials were in the PC phase and the conductive materials (MWNT) were in the PVDF phase, outstanding reflection losses of ca. -57 dB (for the BT and MWNT combination) and -67 dB (for the NF and MWNT combination) were noted and the shielding occurred primarily through absorption. Thus, the approach demonstrates that nanoscopic structuring in the blends can be achieved under macroscopic processing conditions and this strategy can further be explored to design microwave absorbers.


Identification of genetic biomarkers for alloimmunization in sickle cell disease.
Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll-like receptor pathway or in genes previously associated with antibody-mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case-control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.


Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model.
Asthma is a chronic inflammatory disease characterized by T-lymphocyte and eosinophil infiltration, mucus overproduction and airway hyper-responsiveness. The present study examined the therapeutic effects and action mechanism of a saponin-enriched extract of Asparagus cochinchinensis (SEAC) on airway inflammation and remodeling in an ovalbumin (OVA)-induced asthma model. To accomplish this, alterations of the nitric oxide (NO) level, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels, as well as variations in immune cell numbers, immunoglobulin E (IgE) concentration, histopathological structure and inflammatory cytokine levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells or an OVA-induced mouse model of asthma treated with SEAC. The concentration of NO and mRNA levels of COX-2 and iNOS were significantly decreased in the SEAC + LPS-treated RAW264.7 cells compared with the vehicle + LPS-treated RAW264.7 cells. Additionally, in the OVA-induced asthma model, the number of immune cells in the bronchoalveolar lavage fluid, the concentration of OVA-specific IgE, the infiltration of inflammatory cells, the bronchial thickness and the levels of the inflammatory mediators interleukin-4 (IL-4), IL-13 and COX-2 were significantly lower in the OVA + SEAC‑treated group compared with the OVA + vehicle‑treated group. In addition, a significant reduction in goblet cell hyperplasia, peribronchiolar collagen layer thickness and VEGF expression for airway remodeling was detected in the OVA + SEAC‑treated group compared with the OVA + vehicle‑treated group. These findings indicate that SEAC is a suppressor of airway inflammation and remodeling, and may therefore be useful as an anti-inflammatory drug for the treatment of asthma.


Zirconia-Nanoparticle-Reinforced Morphology-Engineered Graphene-Based Foams.
The morphology of graphene-based foams can be engineered by reinforcing them with nanocrystalline zirconia, thus improving their oil-adsorption capacity; This can be observed experimentally and explained theoretically. Low zirconia fractions yield flaky microstructures where zirconia nanoparticles arrest propagating cracks. Higher zirconia concentrations possess a mesh-like interconnected structure where the degree of coiling is dependant on the local zirconia content.


Effect of feed-related farm characteristics on relative values of genetic traits in dairy cows to reduce greenhouse gas emissions along the chain.
Breeding has the potential to reduce greenhouse gas (GHG) emissions from dairy farming. Evaluating the effect of a 1-unit change (i.e., 1 genetic standard deviation improvement) in genetic traits on GHG emissions along the chain provides insight into the relative importance of genetic traits to reduce GHG emissions. Relative GHG values of genetic traits, however, might depend on feed-related farm characteristics. The objective of this study was to evaluate the effect of feed-related farm characteristics on GHG values by comparing the values of milk yield and longevity for an efficient farm and a less efficient farm. The less efficient farm did not apply precision feeding and had lower feed production per hectare than the efficient farm. Greenhouse gas values of milk yield and longevity were calculated by using a whole-farm model and 2 different optimization methods. Method 1 optimized farm management before and after a change in genetic trait by maximizing labor income; the effect on GHG emissions (i.e., from production of farm inputs up to the farm gate) was considered a side effect. Method 2 optimized farm management after a change in genetic trait by minimizing GHG emissions per kilogram of milk while maintaining labor income and milk production at least at the level before the change in trait; the effect on labor income was considered a side effect. Based on maximizing labor income (method 1), GHG values of milk yield and longevity were, respectively, 279 and 143kg of CO2 equivalents (CO2e)/unit change per cow per year on the less efficient farm, and 247 and 210kg of CO2e/unit change per cow per year on the efficient farm. Based on minimizing GHG emissions (method 2), GHG values of milk yield and longevity were, respectively, 538 and 563kg of CO2e/unit change per cow per year on the less efficient farm, and 453 and 441kg of CO2e/unit change per cow per year on the efficient farm. Sensitivity analysis showed that, for both methods, the absolute effect of a change in genetic trait depends on model inputs, including prices and emission factors. Substantial changes in relative importance between traits due to a change in model inputs occurred only in case of maximizing labor income. We concluded that assumptions regarding feed-related farm characteristics affect the absolute level of GHG values, as well as the relative importance of traits to reduce emissions when using a method based on maximizing labor income. This is because optimizing farm management based on maximizing labor income does not give any incentive for lowering GHG emissions. When using a method based on minimizing GHG emissions, feed-related farm characteristics affected the absolute level of the GHG values, but the relative importance of the traits scarcely changed: at each level of efficiency, milk yield and longevity were equally important.


Shear-Rolling Process for Unidirectionally and Perpendicularly Oriented Sub-10-nm Block Copolymer Patterns on the 4 in Scale.
Shear alignment of the block copolymer (BCP) thin film is one of the promising directed self-assembly (DSA) methodologies for the unidirectional alignment of sub-10 nm microdomains of BCPs for next-generation nanolithography and nanowire-grid polarizers. However, because of the differences in the surface/interfacial energies at the top surface/bottom interface, the shear-induced ordering of BCP nanopatterns has been restricted to BCPs with spherical and cylindrical nanopatterns and cannot be realized for high-aspect-ratio perpendicular lamellar structures, which is essential for practical application to semiconductor pattern processes. It is still a difficult challenge to fabricate the unidirectional alignment in a short time over a large area. In this study, we propose an approach for combining the shear-rolling process with the filtered plasma treatment of BCP films for the fabrication of unidirectionally aligned and perpendicularly oriented lamellar nanostructures. This approach enables fabrication within 1 min on a 4 in scale. We treated filtered plasma on the BCP film for perpendicular orientation and executed the hot-rolling process with different roller and stage speeds. Large-scale shear was generated only at the location where the BCP film was in contact with both the roller and stage, effectively applying shear stress to a large area of the BCP film within a short time. The repeated application of this shear-rolling process can achieve a higher level of unidirectional alignment. Our aligned BCP vertical lamellae were used to fabricate a high-aspect-ratio sub-10-nm-wide metallic nanowire array via dry/wet processes. In addition, shear-rolling with chemoepitaxy patterns can achieve higher orientational order and lower defectivity.


Reliability and reproducibility of assessment of corneal epithelial thickness by fourier domain optical coherence tomography.
To analyze the intra-user reliability and inter-user reproducibility of assessment of corneal epithelial thickness by Fourier domain optical coherence tomography. In this consecutive cross-sectional case series performed at a tertiary ocular care institution, 210 eyes of 210 subjects underwent anterior segment Fourier domain optical coherence tomography (FDOCT). A caliper tool software was used to measure the corneal thickness. For the reproducibility measures, the examination was done by 2 examiners (user 1, user 2) within 30 minutes of each other. For the reliability measure, the retest was done by user 1 on the next day, within 30 minutes of the previous test's time. The total corneal thickness, epithelial thickness, and corneal thickness excluding the epithelium were measured. The mean corneal thickness of the population measured by user 1 was 519.5 ± 31.1 μm, 58.6 ± 4.2 μm, and 460.95 ± 31.4 μm for total cornea, epithelium, and non-epithelial cornea, respectively. The difference in results between user 2 and user 1 was 0.8 ± 7.2 μm, 0.23 ± 3.3 μm, and 0.7 ± 8.2 μm for total, epithelium, and non-epithelial cornea, respectively, and the difference in results between the repeated series by user 1 was 0.49 ± 5.7 μm, -0.13 ± 2.7 μm, 0.61 ± 5.4 μm total, epithelium, and non-epithelial cornea, respectively (paired t-test, P > 0.05). Intraclass correlations ranged from 0.87 to 0.99, coefficients of repeatability from 4.5 to 14.11, and coefficient of variation from 2.3% to 11.1%. Fourier domain anterior segment optical coherence tomography is reproducible and reliable for the measurement of epithelial thickness at vertex.


Coal Mine Disasters: Frequency by Month.
Major coal mine disasters (five or more fatalities per accident) in the United States over the past 150 years have tended to occur primarily in the winter months from November through April. Minor accidents (zero to four fatalities per accident) occur at a fairly uniform rate throughout the year. This peak for major disasters is ascribed to effect of barometric minima on the methane content of mine air, to the effect of dry polar air masses in reducing the moisture content of coal dust, and, possibly, to cyclic fatigue of rock structures from cycling barometric pressure. Obvious safety practices are suggested.


Metabolism-dependent activation and toxicity of chemicals in nasal glands.
The mucosae of the nasal passages contain a large amount of glands which express secretory proteins as well as phase I and phase II biotransformation enzymes. In this review the metabolic activation, covalent binding and toxicity of chemicals in the Bowman's glands in the olfactory mucosa, in the sero-mucous glands in the nasal septum and in the lateral nasal glands and maxillary glands around the maxillary sinuses are discussed. Light microscopic autoradiographic studies have demonstrated a selective covalent binding of nasal toxicants and carcinogens such as halogenated hydrocarbons and N-nitrosamines, especially in the Bowman's glands following a single systemic exposure, suggesting a high rate of metabolic activation of chemicals in these glands. Special attention is put on the herbicide dichlobenil which induces necrosis in the olfactory mucosa following a cytochrome-P450-mediated metabolic activation and covalent binding in the Bowman's glands.


Common framework for "virtual lesion" and state-dependent TMS: The facilitatory/suppressive range model of online TMS effects on behavior.
The behavioral effects of Transcranial Magnetic Stimulation (TMS) are often nonlinear; factors such as stimulation intensity and brain state can modulate the impact of TMS on observable behavior in qualitatively different manner. Here we propose a theoretical framework to account for these effects. In this model, there are distinct intensity ranges for facilitatory and suppressive effects of TMS - low intensities facilitate neural activity and behavior whereas high intensities induce suppression. The key feature of the model is that these ranges are shifted by changes in neural excitability: consequently, a TMS intensity, which normally induces suppression, can have a facilitatory effect if the stimulated neurons are being inhibited by ongoing task-related processes or preconditioning. For example, adaptation reduces excitability of adapted neurons; the outcome is that TMS intensities which inhibit non-adapted neurons induce a facilitation on adapted neural representations, leading to reversal of adaptation effects. In conventional "virtual lesion" paradigms, similar effects occur because neurons not involved in task-related processes are inhibited by the ongoing task. The resulting reduction in excitability can turn high intensity "inhibitory" TMS to low intensity "facilitatory" TMS for these neurons, and as task-related neuronal representations are in the inhibitory range, the outcome is a reduction in signal-to-noise ratio and behavioral impairment.


Impact of the Korean Diagnosis-Related Groups payment system on the outcomes of adenotonsillectomy: A single center experience.
To report outcomes with regard to clinical aspects and medical costs of adenotonsillectomy and tonsillectomy at a single institution before and after implementation of the Diagnosis-Related Groups (DRG) payment system in Korea. We retrospectively reviewed the records of patients treated with adenotonsillectomy or tonsillectomy between July 2012 and June 2014. The Korean DRG payment system was applied to seven groups of specific diseases and surgeries including adenotonsillectomy and tonsillectomy from July 2013 at all hospitals in Korea. We divided patients into four groups according whether the fee-for-service (FFS) or DRG payment system was implemented and operation type (FFS-adenotonsillectomy (AT), DRG-AT, FFS-tonsillectomy (T), and DRG-T). A total of 1402 patients were included (485 FFS-AT, 490 DRG-AT, 203 FFS-T, and 223 DRG-T). The total medical cost of the DRG-AT group was significantly lower than that of the FFS-AT group (1191±404 vs. 1110±279 USD, P<0.05). There were no significant differences in length of hospital stay or postoperative complications among groups. The Korean DRG system for adenotonsillectomy and tonsillectomy reduced medical costs and clinical outcomes were not significantly altered by the adoption of the DRG system. 4.


A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response.
The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are closely related orphan nuclear hormone receptors that play a critical role as xenobiotic sensors in mammals. Both receptors regulate the expression of genes involved in the biotransformation of chemicals in a ligand-dependent manner. As the ligand specificity of PXR and CAR have diverged between species, the prediction of in vivo PXR and CAR interactions with a drug are difficult to extrapolate from animals to humans. We report the development of what we believe are novel PXR- and CAR-humanized mice, generated using a knockin strategy, and Pxr- and Car-KO mice as well as a panel of mice including all possible combinations of these genetic alterations. The expression of human CAR and PXR was in the predicted tissues at physiological levels, and splice variants of both human receptors were expressed. The panel of mice will allow the dissection of the crosstalk between PXR and CAR in the response to different drugs. To demonstrate the utility of this panel of mice, we used the mice to show that the in vivo induction of Cyp3a11 and Cyp2b10 by phenobarbital was only mediated by CAR, although this compound is described as a PXR and CAR activator in vitro. This panel of mouse models is a useful tool to evaluate the roles of CAR and PXR in drug bioavailability, toxicity, and efficacy in humans.


Aneurysms of the coronary arteries in the adult. Clincial and angiographic features.
One thousand coronary arteriograms were reviewed to determine the incidence, clinical presentation and angiographic features of aneurysms of the coronary artery (ACA) in adults with angina. Criteria for the angiographic diagnosis are described and the angiographic aspects are emphasized. The incidence of ACA was 1.1%. Saccular and fusiform aneurysms were seen. Single aneurysms were present in 7 patients. One patient had an abdominal aneurysm. Five patients underwent surgery; two had postoperative selective coronary angiography one year later and all five underwent follow-up left ventricular angiography. The most likely etiology of the aneurysms in this series is atherosclerosis.


Stereotactic radiosurgery for a cardiac sarcoma: a case report.
Pulmonary artery intimal sarcoma is an uncommon tumor with a poor prognosis. We report a case of a 75-year-old man with a pulmonary artery sarcoma, recurrent following surgical resection. To palliate symptoms of this recurrence, he underwent CyberKnife stereotactic radiosurgery with a clinical and radiographic response of his treated disease. No acute or sub-acute toxicity was seen until the patient's death due to metastatic disease 10 weeks following treatment. The feasibility and short-term safety of this technique are reviewed, with emphasis on the stereotactic planning considerations, such as mediastinal organ movement and radiation tolerance.


Cyclodextrin-assisted synthesis of tailored mesoporous silica nanoparticles.
Mesoporous silica nanoparticles (MSNs) have sparked considerable interest in drug/gene delivery, catalysis, adsorption, separation, sensing, antireflection coatings and bioimaging because of their tunable structural properties. The shape, size and pore structure of MSNs are greatly influenced by the type of additives used, e.g., solvent and pore-templating agent. Here, we studied the influence of cyclodextrin (CD) molecules on the formation of MSNs. The nanoparticles over 100 nm in diameter were synthesized by surfactant-templated, hydrolysis-polycondensation reactions in the presence of pristine CD (β-CD) or hydroxypropyl-functionalized CDs (HP-γ-CD and HP-β-CD). Depending on the formulation conditions, differently shaped MSNs, such as bean-like, spherical, ellipsoid, aggregate and faceted were generated. The morphology and size of MSNs varied with the CD-type used. Generally, spherical particles were obtained with β-CD, while a faceted morphology was observed for the particles synthesized using HP-CDs. The particle size could be tuned by adjusting the amount of CD used; increasing the CD concentration led to larger particles. MSNs synthesized in the presence of β-CD displayed a smaller particle size than those produced with HP-functional CDs. FTIR, TGA and solid-state 13C NMR demonstrated the adsorption of CDs on the particle surfaces. The proposed concept allows for the synthesis of silica nanoparticles with control over particle shape and size by adjusting the concentration of additives in a simple, one-pot reaction system for a wide range of applications.


Endocardial fibroelastosis occurring in a mother and daughter.
Endocardial fibroelastosis (EFE) in a mother and daughter are reported. This entity has a primary and secondary form. In this case, the 23-year-old mother died 11 months after delivery with findings of EFE. At age 3(1/2) years, the daughter was admitted in congestive heart failure and did not respond to medical management. The autopsy findings revealed EFE. Endocardial fibroelastosis in both mother and daughter is a very rare finding.


Novel somatic mutations in the VHL gene in Swedish archived sporadic renal cell carcinomas.
Frequent loss-of-function somatic mutations of the VHL gene have been detected in sporadic renal cell carcinoma (RCC), indicating that inactivation of the VHL gene plays a critical role in RCC. In this study, we collected 35 archived Swedish sporadic RCCs identified from an epidemiological study on occupational exposure and kidney cancer to test how well stored pathological specimens could be retrieved and analyzed for VHL mutations. Thirty specimens were successfully analyzed with PCR-SSCP and sequencing. Aberrant SSCP bands were detected in 16 out of the 30 samples (53%). Sequencing analysis of the aberrant bands revealed seven deletions, one insertion, one base substitution on a splicing site, six missense mutations, one silent mutation and several base substitutions in the 5' non-coding region and intron 1. Most were novel somatic mutations that have not been reported in sporadic RCC. The mutations were found in three types of non-papillary RCC cases, i.e. 14 clear cells, one granular chromophilic and one sarcomatoid RCC. Interesting multiple mutations were found in three cases (5, 3, 2 mutations, respectively).


Human Papillomavirus-Associated Oral Epithelial Dysplasia: Report of 5 Illustrative Cases from Latin America.
Human papillomavirus-associated oral epithelial dysplasia (HPV-OED) is a distinct oral epithelial disorder characterized by viral cytopathic changes caused by transcriptionally active high-risk HPV. The aim of the present study was to report 5 additional cases from Latin America. Clinical data from five patients with HPV-OED were obtained from the archives of three oral pathology services from Brazil and Chile. All cases were submitted to morphological, p16 expression and in situ hybridization (ISH) for HPV analyses. Four patients were male and one patient was female, with a mean age of 55.4 years. Four patients were HIV seropositive and two were smokers. Three cases affected the buccal mucosa and commissure, one of which had an additional plaque in the soft palate, and one case each occurred on the floor of mouth and lower labial mucosa. Most cases presented as well-demarcated white plaques with a verrucous surface. One case presented multiple lesions ranging from normal to white-colored slightly elevated plaques with a cobblestone surface. Peripheral mucosal pigmentation was observed in two cases. All five cases presented with the characteristic microscopic features of HPV-OED, including severe dysplasia with numerous karyorrhectic and apoptotic cells, full-thickness "block positivity" for p16 and high Ki-67 index (> 90%) sharply demarcated from the adjacent non-dysplastic epithelium. Wide-spectrum DNA ISH-HPV was positive in 4 cases. All patients were treated with conservative surgical excision with no signs of recurrence after a mean of 39-month follow-up. This represents the first series of HPV-OED from Latin America; most cases presented as well-demarcated papillary white plaques affecting the buccal mucosa and commissure of HIV-positive middle-aged men, two of them exhibiting peripheral pigmentation caused by reactive melanocytes. The typical microscopic findings of HPV-OED were observed in all cases, which also showed strong p16 positivity in a continuous band through the full thickness of the epithelium and high Ki67.


Characterization of a Sodium Channel Mutation in Permethrin-Resistant Rhipicephalus sanguineus (Acari: Ixodidae).
The brown dog tick, Rhipicephalus sanguineus (Latrielle) sensu lato, is an important ectoparasite of dogs and occasionally humans, capable of transmitting several pathogens, such as Rickettsia and Ehrlichia, which are of veterinary and medical importance. The brown dog tick is distributed worldwide and has an affinity for human habitations in much of its range. In some populations, lack of integrated pest management plans and overuse of pyrethroid pesticides and other sodium channel inhibitors has resulted in high levels of resistance to permethrin. Recently, a highly conserved region of the R. sanguineus sodium channel was sequenced, indicating that a single nucleotide polymorphism of thymine to cytosine on domain III segment VI of the sodium channel could confer resistance. A molecular assay targeting a point mutation in the sodium channel was developed and optimized to separate ticks expressing permethrin resistance from those from a susceptible colony. Thereafter, multiple field-collected phenotypically permethrin-resistant populations were evaluated using this molecular assay to determine genotype. As confirmed by DNA sequencing, a point mutation was present at a high rate in phenotypically resistant tick populations that was not present in the susceptible strain. These data suggest an additional permethrin resistance mechanism to metabolic resistance, which has been reported for this tick species, and confirm its association with phenotypic resistance. The results of this study further emphasize the need to preserve acaricide chemistry through rotation of active ingredients used to control ectoparasites.


Fatty acid composition of serum lecithin and cholesterol ester in the normal menstrual cycle.
Gonadal hormones and the relative fatty acid composition of serum lecithin and cholesterol ester were studied on four occasions during one cycle in twenty-two regularly menstruating women. The most evident change during the menstrual cycle was a decrease in the sum of polyunsaturated fatty acids of the linoleic series in the late luteal phase. Concomitantly an increase in oleic acid as well as palmitic acid was recorded. These changes were considered to be dietary influenced since a shift of the oleic/linoleic acid ratio is often seen when fat is replaced by sugar and some women are known to increase their intake of refined carbohydrates premenstrually. The only correlation found for fatty acids and hormone levels was a correlation of the ratio oleic/linoleic acids and 17-beta-estradiol. This pattern is not seen after administration of exogenous estrogens and obviously there is a discrepancy between endogenous and exogenous estrogens in this context. Whether physiological fluctuations of sex hormones during the menstrual cycle directly influence the fatty acid composition of serum lecithin and cholesterol ester is uncertain. No changes in dihomo-gamma-linolenic acid or arachidonic acid, the major precursors of prostaglandin synthesis were recorded.


The effect of bolus volume on hyoid kinematics in healthy swallowing.
Hyoid movement in swallowing is biomechanically linked to closure of the laryngeal vestibule for airway protection and to opening of the upper esophageal sphincter. Studies suggest that the range of hyoid movement is highly variable in the healthy population. However, other aspects of hyoid movement such as velocity remain relatively unexplored. In this study, we analyze data from a sample of 20 healthy young participants (10 male) to determine whether hyoid movement distance, duration, velocity, and peak velocity vary systematically with increases in thin liquid bolus volume from 5 to 20 mL. The temporal correspondence between peak hyoid velocity and laryngeal vestibule closure was also examined. The results show that maximum hyoid position and peak velocity increase significantly for 20 mL bolus volumes compared to smaller volumes, and that the timing of peak velocity is closely linked to achieving laryngeal vestibule closure. This suggests that generating hyoid movements with increased power is a strategy for handling larger volumes.


Identification of transthyretin variants by sequential proteomic and genomic analysis.
Transthyretin-associated hereditary amyloidosis (ATTR) is an inherited disease in which variants in the primary structure of transthyretin (TTR; prealbumin) lead to the extracellular polymerization of insoluble protein fibrils, causing organ failure and ultimately death when major organs are involved. We have developed an integrated approach to molecular diagnosis with initial analysis of intact plasma TTR by electrospray ionization mass spectrometry (MS) and referral of positive samples for DNA sequence analysis and real-time PCR to confirm the common Gly6Ser polymorphism. Samples from 6 patients previously diagnosed with ATTR and from 25 controls with (n = 15) or without (n = 10) polyneuropathy were analyzed in a blinded fashion for the presence of variant TTR. TTR protein was extracted with an immunoaffinity resin from 20 microL of archived plasma samples. The purified TTR was reduced with tris(2-carboxyethyl)phosphine and analyzed by MS. The appearance of two peaks (or a single peak shifted in mass indicative of a homozygous variant), including the wild-type mass of 13,761 Da, was indicative of the presence of a variant, and the individual was referred for DNA sequence analysis. MS analysis of intact reduced TTR correctly identified each of six samples known to contain variant TTR. These results were corroborated by subsequent DNA sequence analysis. Additionally, all Gly6Ser polymorphisms were correctly called based on the +30 mass shift and an equal relative abundance of the +30 polymorphism relative to wild-type TTR. No false-positive results were seen. This referral method eliminates the necessity of sequencing most samples and allows screening for the familial forms of amyloidosis in a broad patient population in a timely fashion. This method correctly identified all previously known variants and also identified a novel variant, Val94Ala.


Morphologic Variability of Bone and Soft Tissue in Microtia With Hemifacial Microsomia.
Objective: Microtia patients with hemifacial microsomia (HFM) have a host of distinct anatomical disorder of skeletal and soft tissue asymmetries. The purpose of this study was to assess soft tissue discrepancies in microtia patients with HFM and their correlation with skeletal discrepancies. Methods: A total of 42 patients were enrolled and studied prospectively using a 3-dimensional superimposition and color mapping of the soft and hard tissues. Mirroring techniques created perfectly symmetric models for comparison. Differences between affected and normal sides were evaluated in 5 areas: retroauricular mastoid, malar, maxillary frontal, mandibular frontal, and gonion areas. Pearson correlations were used to assess the relationship between skeletal and soft tissue asymmetry. Results: Hard tissue asymmetry ranged from 0.79 mm (mandibular frontal) to 1.29 mm (malar), while soft tissue asymmetry ranged from 1.34 mm (maxillary frontal) to 5.26 mm (retroauricular mastoid). Correlations between skeletal and soft tissue asymmetry varied, with the strongest correlation observed at the retroauricular mastoid area and the weakest at the maxillary frontal area. Conclusion: There was a high correlation between bone and soft tissue hypoplasia at the retroauricular mastoid area, while the other evaluated areas showed poor correlation between skeletal and soft tissue asymmetries. Clinicians should assess each component separately for optimal treatment planning in microtia patients with HFM.


[Chemotherapy of gestational chorionepithelioma].
The department of Gynecology and Obstetrics of Florence University reports the following findings for the chemotherapy of gestational choriocarcinoma during the period 1962-74. Sixteen cases, 11 of which were rated high risk cases, were given chemotherapy with MTX alone or in association with other cytotoxic agents. In the 12 surviving cases that may be considered the incidence of complete remission (from 4 to 13 years) is 67%. Of the 8 cases rated as cured 3 were high risk cases at the beginning of treatment. Intermittent chemotherapy with MTX only was given by slow intravenous injection at doses of 3 to 4 mg/kg for 24-48 h followed from the 48th h by folinic acid treatment for 1-2 days. This schedule is recommended because of its negligible toxicity as a replacemen for intramuscular MTX in 5-day courses, which carries a fairly high risk of toxicity.


Alpha-thalassemia in Ashkenazi Jews.
Members of a Jewish family of Polish origin were found to have hypochromic, microcytic erythrocytes. By restriction endonuclease analysis of DNA, the propositus, a brother, and an aunt were found to have a single alpha-globin gene on each chromosome 16. Five family members have one chromosome bearing two alpha-genes (5' and 3') with a single alpha-gene on the homologous chromosome. Gene mapping indicated that the chromosome bearing a single alpha-gene arose via an unequal crossover between misaligned 5' and 3' alpha-genes and was introduced into the family from three separate sources. In addition, a Jewish man of Hungarian origin was found to have alpha-thalassemia trait with single alpha-genes on both chromosomes 16 and a survey of 25 Jewish subjects yielded one man of German origin with an alpha-gene deletion. Alpha-thalassemia should be considered in the differential diagnosis of disease in Jewish persons with microcytic, hypochromic erythrocytes.


Dispersal, environmental niches and oceanic-scale turnover in deep-sea bivalves.
Patterns of beta-diversity or distance decay at oceanic scales are completely unknown for deep-sea communities. Even when appropriate data exist, methodological problems have made it difficult to discern the relative roles of environmental filtering and dispersal limitation for generating faunal turnover patterns. Here, we combine a spatially extensive dataset on deep-sea bivalves with a model incorporating ecological dynamics and shared evolutionary history to quantify the effects of environmental filtering and dispersal limitation. Both the model and empirical data are used to relate functional, taxonomic and phylogenetic similarity between communities to environmental and spatial distances separating them for 270 sites across the Atlantic Ocean. This study represents the first ocean-wide analysis examining distance decay as a function of a broad suite of explanatory variables. We find that both strong environmental filtering and dispersal limitation drive turnover in taxonomic, functional and phylogenetic composition in deep-sea bivalves, explaining 26 per cent, 34 per cent and 9 per cent of the variation, respectively. This contrasts with previous suggestions that dispersal is not limiting in broad-scale biogeographic and biodiversity patterning in marine systems. However, rates of decay in similarity with environmental distance were eightfold to 44-fold steeper than with spatial distance. Energy availability is the most influential environmental variable evaluated, accounting for 3.9 per cent, 9.4 per cent and 22.3 per cent of the variation in functional, phylogenetic and taxonomic similarity, respectively. Comparing empirical patterns with process-based theoretical predictions provided quantitative estimates of dispersal limitation and niche breadth, indicating that 95 per cent of deep-sea bivalve propagules will be able to persist in environments that deviate from their optimum by up to 2.1 g m(-2) yr(-1) and typically disperse 749 km from their natal site.


Enhancer evolution across 20 mammalian species.
The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution.


Single amino acid substitutions in the severe acute respiratory syndrome coronavirus spike glycoprotein determine viral entry and immunogenicity of a major neutralizing domain.
Neutralizing antibodies (NAbs) against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) spike (S) glycoprotein confer protection to animals experimentally infected with the pathogenic virus. We and others previously demonstrated that a major mechanism for neutralizing SARS-CoV was through blocking the interaction between the S glycoprotein and the cellular receptor angiotensin-converting enzyme 2 (ACE2). In this study, we used in vivo electroporation DNA immunization and a pseudovirus-based assay to functionally evaluate immunogenicity and viral entry. We characterized the neutralization and viral entry determinants within the ACE2-binding domain of the S glycoprotein. The deletion of a positively charged region Sdelta(422-463) abolished the capacity of the S glycoprotein to induce NAbs in mice vaccinated by in vivo DNA electroporation. Moreover, the Sdelta(422-463) pseudovirus was unable to infect HEK293T-ACE2 cells. To determine the specific residues that contribute to related phenotypes, we replaced eight basic amino acids with alanine. We found that a single amino acid substitution (R441A) in the full-length S DNA vaccine failed to induce NAbs and abolished viral entry when pseudoviruses were generated. However, another substitution (R453A) abolished viral entry while retaining the capacity for inducing NAbs. The difference between R441A and R453A suggests that the determinants for immunogenicity and viral entry may not be identical. Our findings provide direct evidence that these basic residues are essential for immunogenicity of the major neutralizing domain and for viral entry. Our data have implications for the rational design of vaccine and antiviral agents as well as for understanding viral tropism.


Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men.
Testosterone (T) exerts negative feedback on the hypothalamo-pituitary (GnRH-LH) unit, but the relative roles of the CNS and pituitary are not established. We postulated that relatively greater LH responses to flutamide (brain-permeant antiandrogen) than bicalutamide (brain-impermeant antiandrogen) should reflect greater feedback via CNS than pituitary/peripheral androgen receptor-dependent pathways. To this end, 24 healthy men ages 20-73 yr, BMI 21-32 kg/m2, participated in a prospective, placebo-controlled, randomized, double-blind crossover study of the effects of antiandrogen control of pulsatile, basal, and entropic (pattern regularity) measurements of LH secretion. Analysis of covariance revealed that flutamide but not bicalutamide 1) increased pulsatile LH secretion (P = 0.003), 2) potentiated the age-related abbreviation of LH secretory bursts (P = 0.025), 3) suppressed incremental GnRH-induced LH release (P = 0.015), and 4) decreased the regularity of GnRH-stimulated LH release (P = 0.012). Furthermore, the effect of flutamide exceeded that of bicalutamide in 1) raising mean LH (P = 0.002) and T (P = 0.017) concentrations, 2) accelerating LH pulse frequency (P = 0.013), 3) amplifying total (basal plus pulsatile) LH (P = 0.002) and T (P < 0.001) secretion, 4) shortening LH secretory bursts (P = 0.032), and 5) reducing LH secretory regularity (P < 0.001). Both flutamide and bicalutamide elevated basal (nonpulsatile) LH secretion (P < 0.001). These data suggest the hypothesis that topographically selective androgen receptor pathways mediate brain-predominant and pituitary-dependent feedback mechanisms in healthy men.


Attitudes Toward Mobile Apps for Pandemic Research Among Smartphone Users in Germany: National Survey.
During the COVID-19 pandemic, but also in the context of previous epidemic diseases, mobile apps for smartphones were developed with different goals and functions, such as digital contact tracing, test management, symptom monitoring, quarantine compliance, and epidemiological and public health research. The aim of this study was to explore the potential for the acceptance of research-orientated apps (ROAs) in the German population. To this end, we identified distinctive attitudes toward pandemic apps and data sharing for research purposes among smartphone users in general and with a focus on differences in attitudes between app users and nonusers in particular. We conducted a cross-sectional, national, telephone-based survey of 1003 adults in Germany, of which 924 were useable for statistical analysis. The 17-item survey assessed current usage of pandemic apps, motivations for using or not using pandemic apps, trust in app distributors and attitudes toward data handling (data storage and transmission), willingness to share coded data with researchers using a pandemic app, social attitudes toward app use, and demographic and personal characteristics. A vast majority stated that they used a smartphone (778/924, 84.2%), but less than half of the smartphone users stated that they used a pandemic app (326/778, 41.9%). The study focused on the subsample of smartphone users. Interestingly, when asked about preferred organizations for data storage and app distribution, trust in governmental (federal or state government, regional health office), public-appointed (statutory health insurance), or government-funded organizations (research institutes) was much higher than in private organizations (private research institutions, clinics, health insurances, information technology [IT] companies). Having a university degree significantly (P<.001) increased the likelihood of using a pandemic app, while having a migration background significantly (P<.001) decreased it. The overwhelming majority (653/778, 83.9%) of smartphone users were willing to provide their app data for state-funded research. Regarding attitudes toward app usage, striking differences between users and nonusers were found. Almost all app users (317/327, 96.9%) stated they would be willing to share data, whereas only 74.3% (336/452) of nonusers supported data sharing via an app. Two-thirds (216/326, 66.3%) of app users fully or rather agreed with the statement that using a pandemic app is a social duty, whereas almost the same proportion of nonusers entirely or rather disagreed with that statement (273/451, 60.5%). These findings indicate a high potential for the adoption of ROAs among smartphone users in Germany as long as organizational providers engaged in development, operation, and distribution are state-funded or governmental institutions and transparency about data-using research institutions is provided.


Characteristics Associated with In-Hospital Death among Commercially Insured Decedents with Cancer.
A majority of patients with poor-prognosis cancer express a preference for in-home death; however, in-hospital deaths are common. We sought to identify characteristics associated with in-hospital death. Case series. Commercially insured patients with cancer who died between July 2010 and December 2013 and who had at least two outpatient visits at a tertiary cancer center during the last six months of life. Patient characteristics, healthcare utilization, and in-hospital death (primary outcome) were ascertained from institutional records and healthcare claims. Bivariate and multivariable analyses were used to evaluate the association of in-hospital death with patient characteristics and end-of-life outcome measures. We identified 904 decedents, with a median age of 59 years at death. In-hospital death was observed in 254 patients (28%), including 110 (12%) who died in an intensive care unit. Hematologic malignancy was associated with a 2.57 times increased risk of in-hospital death (95% confidence interval [CI] 1.91-3.45, p < 0.001), and nonenrollment in hospice was associated with a 14.5 times increased risk of in-hospital death (95% CI 9.81-21.4, p < 0.001). Time from cancer diagnosis to death was also associated with in-hospital death (p = 0.003), with the greatest risk among patients dying within six months of cancer diagnosis. All significant associations persisted in multivariable analyses that were adjusted for baseline characteristics. In-hospital deaths are common among commercially insured cancer patients. Patients with hematologic malignancy and patients who die without receiving hospice services have a substantially higher incidence of in-hospital death.


Modulation of Lactobacillus casei in ileal and fecal samples from healthy volunteers after consumption of a fermented milk containing Lactobacillus casei DN-114 001Rif.
Lactobacillus casei DN-114 001 is a probiotic strain able to interact with the immune system and to interfere with gastrointestinal pathogens. The derived strain DN-114 001Rif was studied during its transit through the upper and distal intestine of human volunteers. Seven volunteers participated in the study, which involved intestinal intubation to sample ileal contents and collection of fecal samples, with a wash-out period of 8 days between the 2 steps. The retrieval of the probiotic was analyzed in the ileum every 2 h for 8 h following the ingestion of one dose of the test product and in the feces prior to, during, and after daily consumption of the test product for 8 days. Persistence of the probiotic amplifiable DNA was assessed using temporal temperature gradient gel electrophoresis and real-time PCR. Fluorescent in situ hybridization allowed analysis of the composition of the dominant digestive microbiota. The ingestion of L. casei DN-114 001Rif led to a significant and transient increase of its amplifiable DNA in ileal and fecal samples. This is related to a high stability in the composition of dominant groups of the gut microbiota. Data from ileal samples are scarce and our study confirms the potentiality for interaction between probiotics and the human immune system.


Differential effects of patient symptom subtypes on informal hospice caregiver depression.
ABSTRACTObjective:Researchers sought to determine the extent to which burden related to patients' symptom subtypes could predict informal hospice caregiver depression, and to illustrate the differences between caregivers who experience suicidal ideation and those who do not. Informal caregivers recruited from a not-for-profit community-based hospice agency participated in a cross-sectional survey. Self-report questionnaires assessed caregiver burden associated with patient symptomatology (via a modified version of the Memorial Symptom Assessment Scale-Short Form) and caregiver depressive symptoms, including suicidal ideation (measured by the Patient Health Questionnaire-9). Multiple regressions evaluated the unique predictability of patients' symptom subtypes on caregiver depression. Exploratory analyses examined mean differences of study variables between participants who did and did not endorse suicidal ideation. Caregiver burden related to patients' psychological symptoms accounted for significant variance in caregiver depression scores when controlling for burden related to physical symptoms. Among 229 caregivers (M age = 61.4 years), 12 reported suicidal ideation, where 6 of the 12 were male, despite male caregivers comprising less than 20% of the total sample. Burden associated with patients' psychological symptoms uniquely contributed to caregiver depression, further highlighting the clinical utility and necessity for hospice providers to address the emotional needs of patients and their caregivers alike. Developing clinical procedures to identify and respond to such needs would not only behoove hospice agencies, but it would likely enhance the caregiving experience holistically, which might be particularly imperative for male caregivers.


Liquid culture medium for the rapid cultivation of Helicobacter pylori from biopsy specimens.
The goal of this study was to develop a liquid culture medium for the rapid isolation, cultivation, identification and subsequent antibiotics susceptibility testing of Helicobacter pylori directly from biopsy specimens. Five liquid media were tested: Ham's F-12, Brucella broth, tryptic soybroth, brain heart infusion broth and Mueller-Hinton broth. After optimisation of the medium, it was applied in order to investigate biopsy samples from 150 patients with gastro-duodenal disorders and compared with traditional culture methods, microscopy and an H. pylori-specific TaqMan real-time polymerase chain reaction (PCR). The most reliable and rapid growth of H. pylori, even at a small inoculum size, was obtained in Ham's F-12 medium with 5% horse serum. The developed system allowed the primary isolation of H. pylori in clinical samples and provided 87% sensitivity and 100% specificity.


Burnout among nurses working in medical and educational centers in Shahrekord, Iran.
Nursing burnout is the main characteristic of job stress that is a delayed reaction to chronic stressful situations in the workplace which could affect nurses who do not have sufficient emotional energy to cope and communicate with different types of patients. There is also sometimes this belief that they do not have the required capabilities for their jobs. The aim of this study was the evaluation of burnout among nurses working in medical and educational centers in Shahrekord. This descriptive study was performed on 340 nurses working in medical and educational centers in Shahrekord in 2009. Samples were selected using proportionate random sampling. Demographic information and the Maslach Burnout Inventory (MBI) were filled in for all nurses. Burnout was considerable among nurses. The results showed that 34.6, 28.8, and 95.7% of the nurses had emotional exhaustion (EE), high depersonalization (DP), and high reduced personal accomplishment (PA), respectively. The mean scores (± standard deviation) for EE, DP, and PA were 22.77 (12.44), 6.99 (6.23), and 32.20 (9.26), respectively. Our results showed that burnout was noticeable among nurses working in medical and educational centers in Shahrekord. Disproportionate relationship between the number of nurses, workload, and income was the most important factor affecting nursing burnout. Due to the importance of nursing in the health-care system, policy makers should adopt suitable strategies for increasing the satisfaction of nurses.


Cross-reactive CD8+ T cell epitopes identified in US adolescent minorities.
Vaccines designed to bring forth CD8+ T cell responses in different racial and ethnic groups will require inclusion of T cell epitopes presented by various MHC class I molecules. This study was designed to identify new CD8+ T cell epitopes in HIV-infected African American and Hispanic youth as well as to determine the frequency of responses to both novel and previously described HIV-1 epitopes in a cohort of racially and ethnically diverse individuals. We found 8 MHC class I-restricted CD8+ T cell epitopes that had not been previously described, another 8 epitopes that were restricted by class I alleles not previously associated with these epitopes, and 8 additional epitopes that have been described previously. In a larger cohort, we demonstrated that 11 (69%) of these 16 newly described immunogens were recognized by individuals of different race or ethnicity. Most HIV-1-specific CD8+ T cell epitopes identified were either novel or restricted by alternative MHC class I alleles. Frequent recognition of several of these CTL epitopes in persons of diverse racial backgrounds bodes well for the development of a broadly reactive HIV-1 vaccine.


Effects of protein phosphatase inhibitors on the regulation of insulin-sensitive enzymes within rat epididymal fat-pads and cells.
1. The effects of the protein phosphatase inhibitors okadaic acid and microcystin LR on the regulation by insulin of pyruvate dehydrogenase and acetyl-CoA carboxylase have been studied in rat epididymal fat-pads and isolated cells. These inhibitors both completely blocked the phosphatase activity (against phosphorylase a) present in extracts of epididymal fat-pads, with half-maximal effects in the nanomolar range. 2. Okadaic acid treatment of pads and cells lowered the activity of acetyl-CoA carboxylase assayed in tissue extracts, both before and after treatment of the extracts with the activator, citrate. Further, okadaic acid treatment abolished the 2-3-fold difference in activity observed between extracts from control and insulin-treated tissues, assayed without prior treatment with citrate. 3. Incubation of pads with [32P]Pi, sufficient to label the intracellular pool of ATP, demonstrated that okadaic acid increased the overall phosphorylation of acetyl-CoA carboxylase on a number of distinct sites, as judged by two-dimensional mapping of tryptic peptides. These included the 'I-peptide' [Brownsey & Denton (1982) Biochem. J. 202, 77-86], the phosphorylation of which may be associated with the stimulation of the activity of the enzyme by insulin, as well as inhibitory phosphorylation sites. 4. Incubation with 1 microM-okadaic acid had no effect on the basal level of active pyruvate dehydrogenase apparent after tissue extraction, but abolished the 2-3-fold increase in this parameter which was elicited by insulin in the absence of okadaic acid. However, okadaic acid treatment did not affect the persistent increase in active pyruvate dehydrogenase levels which was apparent in mitochondria subsequently isolated from insulin-treated pads and re-incubated with an oxidizable substrate. It is concluded that the effects of okadaic acid are exerted through changes in metabolite concentrations rather than some direct action on the signalling pathway whereby insulin stimulates pyruvate dehydrogenase. 5. Microcystin LR did not mimic the effects of okadaic acid on intact cells and pads described above.


The phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) by engineered surfaces with electrostatically or covalently immobilized VEGF.
Growth factors are a class of signaling proteins that direct cell fate through interaction with cell-surface receptors. Although a myriad of possible cell fates stems from a growth factor binding to its receptor, the signaling cascades that result in one fate over another are still being elucidated. One possible mechanism by which nature modulates growth factor signaling is through the method of presentation of the growth factor--soluble or immobilized (matrix bound). Here we present the methodology to study signaling of soluble versus immobilized VEGF through VEGFR-2. We have designed a strategy to covalently immobilize VEGF using its heparin-binding domain to orient the molecule (bind) and a secondary functional group to mediate covalent binding (lock). This bind-and-lock approach aims to allow VEGF to assume a bioactive orientation before covalent immobilization. Surface plasmon resonance (SPR) demonstrated heparin and VEGF binding with surface densities of 60 ng/cm2 and 100 pg/cm2, respectively. ELISA experiments confirmed VEGF surface density and showed that electrostatically bound VEGF releases in cell medium and heparin solutions while covalently bound VEGF remains immobilized. Electrostatically bound VEGF and covalently bound VEGF phosphorylate VEGFR-2 in both VEGFR-2 transfected cells and VEGFR-2 endogenously producing cells. HUVECs plated on VEGF functionalized surfaces showed different morphologies between surface-bound VEGF and soluble VEGF. The surfaces synthesized in these studies allow for the study of VEGF/VEGFR-2 signaling induced by covalently bound, electrostatically bound, and soluble VEGF and may provide further insight into the design of materials for the generation of a mature and stable vasculature.


Transurethral Electrovaporization of Bladder Diverticulum: An Alternative to Open or Laparoscopic Bladder Diverticulectomy.
We used transurethral electrovaporization of the diverticular mucosa as the primary treatment for an acquired bladder diverticulum in a female patient. The bladder diverticulum was secondary to bladder outlet obstruction from a previous pubovaginal sling. In comparison to either open or laparoscopic bladder diverticulectomy, transurethral electrovaporization of the bladder diverticulum was effective in significantly reducing the diverticular size while being less invasive, requiring a short operative time, and a quick patient recovery.


Acute stroke: delays to presentation and emergency department evaluation.
To document prehospital and inhospital time intervals from stroke onset to emergency department evaluation and to identify factors associated with presentation to the ED within 3 hours of symptom onset, the current time window for thrombolytic therapy. Patients admitted through the ED with a diagnosis of stroke were identified through admitting logs. Time intervals were obtained from EMS runsheets and ED records. Information regarding first medical contact, education, and income was obtained by patient interview. Baseline variables were analyzed to assess association with ED arrival within 3 hours of symptom onset; variables significant on univariate analysis were placed in a multivariable model. There were 151 stroke patients (59% white and 41% black). Time of stroke onset and time to ED arrival were documented for 119 patients (79%). The median time from stroke onset to ED arrival was 5.7 hours; 46 patients (30%) presenting within 3 hours. Of those with times recorded, the median time from stroke onset to EMS arrival was 1.7 hours. Multivariable logistic regression identified use of EMS (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.3 to 12.1) and white race (OR, 3.5; 95% CI, 1.3 to 10) as being independently associated with ED arrival within 3 hours of symptom onset. Median time from ED arrival to physician evaluation was 20 minutes. Median time from ED arrival to computed tomographic evaluation was 72 minutes. When patients were asked the main reason they sought medical attention, 40% (60/141) of those able to be interviewed said that they themselves did not decide to seek medical attention, but rather a friend or family member told them they should go to the hospital. The median time from stroke onset to ED evaluation was 5.7 hours, with almost a third of patients presenting within 3 hours. Use of EMS and white race were independently associated with arrival within 3 hours.


Development and characterization of a continuous cell line PSCF from Puntius sophore.
A continuous Puntius sophore caudal-fin (PSCF) cell line of the pool barb Puntius sophore, an important freshwater food and ornamental fish of Asia and South East Asia, was developed from the caudal fin for the first time. The cell line was optimally maintained at 28° C in Leibovitz-15 (L-15) medium supplemented with 10% foetal bovine serum (FBS). The cytogenetic analysis revealed a diploid count of 50 chromosomes at 25th and 50th passage and 52 chromosomes at passage 70, 85 and 100. The viability of the PSCF cell lines was 75% after 6 months of storage in liquid nitrogen (-196° C). The most striking feature of the PSCF cells was its high increased growth ratio as evident from the population doubling time of 25 h at passage 100. The origin of the cell lines was confirmed by the amplification of 581 and 655 bp fragments of 16 S rRNA and cytochrome oxidase subunit I (COI) of mitochondrial DNA (mtDNA) genes, respectively. The PSCF cells were successfully transfected with green fluorescent protein (GFP) reporter plasmids and the expression of GFP gene in the cells indicated the potential utility of the cells in gene expression studies.


Species-specific differences of the spectroscopic properties of P700: analysis of the influence of non-conserved amino acid residues by site-directed mutagenesis of photosystem I from Chlamydomonas reinhardtii.
We applied optical spectroscopy, magnetic resonance techniques, and redox titrations to investigate the properties of the primary electron donor P700 in photosystem I (PS I) core complexes from cyanobacteria (Thermosynechococcus elongatus, Spirulina platensis, and Synechocystis sp. PCC 6803), algae (Chlamydomonas reinhardtii CC2696), and higher plants (Spinacia oleracea). Remarkable species-specific differences of the optical properties of P700 were revealed monitoring the (3P700-P700) and (P700+.-P700) absorbance and CD difference spectra. The main bleaching band in the Qy region differs in peak position and line width for the various species. In cyanobacteria the absorbance of P700 extends more to the red compared with algae and higher plants which is favorable for energy transfer from red core antenna chlorophylls to P700 in cyanobacteria. The amino acids in the environment of P700 are highly conserved with two distinct deviations. In C. reinhardtii a Tyr is found at position PsaB659 instead of a Trp present in all other organisms, whereas in Synechocystis a Phe is found instead of a Trp at the homologous position PsaA679. We constructed several mutants in C. reinhardtii CC2696. Strikingly, no PS I could be detected in the mutant YW B659 indicating steric constraints unique to this organism. In the mutants WA A679 and YA B659 significant changes of the spectral features in the (3P700-P700), the (P700+.-P700) absorbance difference and in the (P700+.-P700) CD difference spectra are induced. The results indicate structural differences among PS I from higher plants, algae, and cyanobacteria and give further insight into specific protein-cofactor interactions contributing to the optical spectra.


HIV/AIDS and maternity care in Kenya: how fears of stigma and discrimination affect uptake and provision of labor and delivery services.
Although policies and programs exist to promote safe motherhood in sub-Saharan Africa, maternal health has not improved and may be deteriorating in some countries. Part of the explanation may be the adverse effects of HIV/AIDS on maternity care. We conducted a study in Kisumu, Kenya to explore how fears related to HIV/AIDS affect women's uptake and health workers' provision of labor and delivery services. In-depth qualitative interviews with 17 maternity workers, 14 pregnant or postpartum women, four male partners and two traditional birth attendants; as well as structured observations of 22 births; were conducted at four health facilities. Participants reported that fears of HIV testing; fears of involuntary disclosure of HIV status to others, including spouses; and HIV/AIDS stigma are among the reasons that women avoid delivering in health facilities. Maternity workers now have to take into account the HIV status of the women they serve (as well as their own fears of becoming infected and stigmatized) but do not seem to be adequately prepared to handle issues related to consent, confidentiality and disclosure. Importantly, it appeared that women of unknown HIV status during labor and delivery were likely to be targets of stigma and discriminatory practices and that these women were not receiving needed counseling services. The findings suggest that increasing infection control precautions will not be enough to address the challenges faced by maternity care providers in caring for women in high-HIV-prevalence settings. Maternity workers need enhanced culturally sensitive training regarding consent, confidentiality and disclosure. Furthermore, this study points to the necessity of paying more attention to the care of women of unknown HIV-serostatus during labor and delivery. Such interventions may improve the quality of maternity care, increase utilization and contribute to overall improvements in maternal health, while also enhancing prevention of mother-to-child-transmission and HIV care.


Comparison of outcome of patients with unstable angina and non-Q-wave acute myocardial infarction with and without prior coronary artery bypass grafting (Thrombolysis in Myocardial Ischemia III Registry).
The aim of this study was to characterize patients with and without prior coronary artery bypass grafting (CABG) among a prospectively identified cohort of patients presenting with unstable angina or non-Q-wave myocardial infarction. Patients in the Thrombolysis in Myocardial Infarction phase III Registry Prospective Study presented within 96 hours of an episode of unstable angina or non-Q-wave acute myocardial infarction. Of 2,048 patients, 336 (16.4%) had prior CABG. Compared with those without prior CABG, patients were the same age, but were more likely to be men, white, diabetic, have a history of angina or myocardial infarction, to have received anti-ischemic medications in the prior week, and to receive intravenous heparin or nitroglycerin, or both, during hospitalization. They were equally likely to undergo coronary angioplasty or CABG. Death or nonfatal myocardial infarction occurred by day 10 in 4.5% of patients with prior CABG and 2.8% of patients without prior CABG (p = 0.11); and by day 42 in 7.7% and 5.1%, respectively (p = 0.03). The composite of death, myocardial infarction, or recurrent ischemia at 1 year was more common among patients with prior CABG (39.3% vs 30.2%, p = 0.002). By multiple logistic regression, prior CABG was not independently associated with the occurrence of death or myocardial infarction, or the composite of death, myocardial infarction, or recurrent ischemia either at 6 weeks or at 1 year. The likelihood of recurrent ischemic events is greater among patients with than without prior CABG, but is not likely explained by differences in baseline or treatment characteristics which reflect the degree of underlying cardiac disease.


A cross-sectional study of patients with and without substance use disorders in Community Mental Health Centres.
Epidemiological studies have consistently established high comorbidity between psychiatric disorders and substance use disorders (SUD). This comorbidity is even more prominent when psychiatric populations are studied. Previous studies have focused on inpatient populations dominated by psychotic disorders, whereas this paper presents findings on patients in Community Mental Health Centres (CMHCs) where affective and anxiety disorders are most prominent. The purpose of this study is to compare patients in CMHCs with and without SUD in regard to differences in socio-demographic characteristics, level of morbidity, prevalence of different diagnostic categories, health services provided and the level of improvement in psychiatric symptoms. As part of the evaluation of the National Plan for Mental Health, all patients seen in eight CMHCs during a 4-week period in 2007 were studied (n = 2154). The CMHCs were located in rural and urban areas of Norway. The patients were diagnosed according to the ICD-10 diagnoses and assessed with the Health of the Nation Outcome Scales, the Alcohol Use Scale and the Drug Use Scale. Patients with SUD in CMHCs are more frequently male, single and living alone, have more severe morbidity, less anxiety and mood disorders, less outpatient treatment and less improvement in regard to recovery from psychological symptoms compared to patients with no SUD. CMHCs need to implement systematic screening and diagnostic procedures in order to detect the special needs of these patients and improve their treatment.


Can sugars be produced from fatty acids? A test case for pathway analysis tools.
In recent years, several methods have been proposed for determining metabolic pathways in an automated way based on network topology. The aim of this work is to analyse these methods by tackling a concrete example relevant in biochemistry. It concerns the question whether even-chain fatty acids, being the most important constituents of lipids, can be converted into sugars at steady state. It was proved five decades ago that this conversion using the Krebs cycle is impossible unless the enzymes of the glyoxylate shunt (or alternative bypasses) are present in the system. Using this example, we can compare the various methods in pathway analysis. Elementary modes analysis (EMA) of a set of enzymes corresponding to the Krebs cycle, glycolysis and gluconeogenesis supports the scientific evidence showing that there is no pathway capable of converting acetyl-CoA to glucose at steady state. This conversion is possible after the addition of isocitrate lyase and malate synthase (forming the glyoxylate shunt) to the system. Dealing with the same example, we compare EMA with two tools based on graph theory available online, PathFinding and Pathway Hunter Tool. These automated network generating tools do not succeed in predicting the conversions known from experiment. They sometimes generate unbalanced paths and reveal problems identifying side metabolites that are not responsible for the carbon net flux. This shows that, for metabolic pathway analysis, it is important to consider the topology (including bimolecular reactions) and stoichiometry of metabolic systems, as is done in EMA. Supplementary data are available at Bioinformatics online.


The interaction of particulate horseradish peroxidase (HRP)-anti HRP immune complexes with mouse peritoneal macrophages in vitro.
The uptake, distribution, and fate of particulate horseradish peroxidase (HRP)-anti HRP aggregates has been studied in homogeneous monolayers of mouse macrophages in vitro. Macrophages rapidly interiorize the immune complexes after binding to the cell surface. The rate of interiorization is maximal for complexes formed in a broad zone of 4-fold antibody excess to equivalence and corresponds to a rate of 10% of the administered load/10(6) cells per hour. This rate is 4000-fold greater than the uptake of soluble HRP. The binding and endocytosis of HRP-anti HRP by macrophages is mediated by the trypsin insensitive F(c) receptor. Cytochemically, intracellular HRP is localized within membrane bound vacuoles. After uptake of HRP, the enzymatic activity is degraded exponentially with a half-life of 14-18 hr until enzyme is no longer detectable. This half-life is twice as long as that previously observed for soluble uncomplexed HRP and is related to the combination of HRP with anti-HRP rather than the absolute amounts of enzyme or antibody ingested. The half-life of HRP-(125)I was 30 hr. Exocytosis of cell associated enzyme or TCA precipitable counts was not detected, nor were persistent surface complexes demonstrable. The extensive capacity of macrophages to interiorize and destroy large amounts of antigen after the formation of antibody illustrates a role of this cell in the efferent limb of the immune response.


Roles of the auxiliary genes and AP-1 binding site in the long terminal repeat of feline immunodeficiency virus in the early stage of infection in cats.
To examine the roles of auxiliary genes and the AP-1 binding site in the long terminal repeat of feline immunodeficiency virus (FIV) in vivo, three mutant viruses, which are defective in the vif gene ([delta]vif), ORF-A gene (deltaORF-A), and AP-1 binding site (deltaAP-1), and wild-type virus as a positive control were separately inoculated into three specific-pathogen-free cats. These cats were assessed by measuring the number of proviral DNA copies in peripheral blood mononuclear cells (PBMCs), the CD4/CD8 ratio and antibody responses to FIV for 16 weeks and then examining histological changes at necropsy. Although viral DNAs were detected in PBMCs from all 12 cats to various degrees until 16 weeks postinoculation, no virus was recovered from PBMCs of cats infected with (delta)vif virus during the observation period. However, a very weak antibody response was induced in one cat infected with the (delta)vif virus. In contrast, despite the successful recovery of virus from both groups of cats infected with deltaORF-A and deltaAP-1 virus, antibody responses and decrease in the CD4/CD8 ratio in the groups were milder than those in cats infected with wild-type virus. Furthermore, the numbers of proviral DNA copies in PBMCs from the two groups were not able to reach the level in cats infected with wild-type virus during the observation period. From these results, we conclude that these mutant viruses are still infectious for cats but failed in efficient viral replication and suggest that these auxiliary genes and enhancer element are important or essential to full viral replication kinetics and presumably to full pathogenicity during the early stage of infection in vivo.


A phase diagram for microfabrication of geometrically controlled hydrogel scaffolds.
Hydrogels are considered as excellent candidates for tissue substitutes by virtue of their high water content and biphasic nature. However, the fact that they are soft, wet and floppy renders them difficult to process and use as custom-designed scaffolds. To address this problem alginate hydrogels were modeled and characterized by measuring stress-strain and creep behavior as well as viscosity as a function of sodium alginate concentration, cross-linking time and calcium ion concentration. The gels were then microfabricated into scaffolds using the pressure-assisted microsyringe. The mechanical and viscous characteristics were used to generate a processing window in the form of a phase diagram which describes the fidelity of the scaffolds as a function of the material and machine parameters. The approach can be applied to a variety of microfabrication methods and biomaterials in order to design well-controlled custom scaffolds.