Prevalence, awareness, and burden of major depressive disorder in urban China.
This cross-sectional study examined the prevalence and burden of major depressive disorder (MDD) among adults in urban China. Data were included from the 2012 China National Health and Wellness Survey. Respondents self-reporting physician diagnosis of depression and screening positive for MDD (Patient Health Questionnaire-9), plus those screening positive for MDD, but undiagnosed and not experiencing depression, were compared with non-depressed controls. Outcomes included health-related quality of life (HRQoL), productivity loss, and resource utilization. Multivariable models assessed outcomes as a function of MDD, controlling for covariates. MDD prevalence was 6.0%; only 8.3% of these respondents were diagnosed, among whom 51.5% currently used prescription medication for depression. Adults with MDD (diagnosed or undiagnosed) reported significantly poorer HRQoL and greater productivity loss and resource utilization than controls. MDD in urban China may be under-diagnosed and undertreated. Awareness and better access to treatments may help alleviate the burden of MDD.


Regulation of Actin Bundle Mechanics and Structure by Intracellular Environmental Factors.
The mechanical and structural properties of actin cytoskeleton drive various cellular processes, including structural support of the plasma membrane and cellular motility. Actin monomers assemble into double-stranded helical filaments as well as higher-ordered structures such as bundles and networks. Cells incorporate macromolecular crowding, cation interactions, and actin-crosslinking proteins to regulate the organization of actin bundles. Although the roles of each of these factors in actin bundling have been well-known individually, how combined factors contribute to actin bundle assembly, organization, and mechanics is not fully understood. Here, we describe recent studies that have investigated the mechanisms of how intracellular environmental factors influence actin bundling. This review highlights the effects of macromolecular crowding, cation interactions, and actin-crosslinking proteins on actin bundle organization, structure, and mechanics. Understanding these mechanisms is important in determining in vivo actin biophysics and providing insights into cell physiology.


Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation.
As the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated. We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated. A comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P < 0.05, P < 0.01). Bone morphogenetic protein (BMP)2 activity was enhanced with both increased TSH concentration and increased time. The protein levels of Runx2 and osterix were increased in a dose-dependent manner. The circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.


[Effects of hormonal contraceptives on parameters of lipid metabolism (author's transl)].
Constant rise of triglycerides and low but regular increase of phospholipid concentrations in serum were observed as a consequence of intake of single-phase hormonal contraceptives. This has been paralleled by inconstant, moderate rise in cholesterol. Those effects are likely to demonstrate dependence on oestrogen amounts of the preparations in question as well as on both quality and quantity of the progestagenic component. Rising concentrations of low density lipoproteins were recordable with regularity. However, variegated results so far have been obtained from studies into the behaviour of high-density lipoproteins. -The mechanism of origin of those alterations, which usually did not surpass normal limits, and their relevance to clinical practice are discussed.


[Mechanisms of release of leucocytic pyrogen].
Mechanisms of the production and release of leucocytic pyrogen (LP) from peritoneal polymorphonuclear leucocytes (PMN) from rabbits were studied in vitro. The following results were obtained. 1) The fever curves of the microsomal and the lysosomal fractions had a later onset and were longer lasting than those from the extracellular fluid. The fever curves of the supernatant of 105,000 g showed the typical response of endogenous pyrogen characterized by a rapid onset and short lasting fever, as shown by the extracellular fluid. 2) The pyrogenicity of LP was the most potent at 60 min while the 105,000 g supernatant was most potent at 30 min after PMN incubation at 37 degrees C. 3) The extracellular protein attained the maximum level at 30 min after incubation of PMN, while the protein content in the supernatant of 105,000 g of PMN decreased gradually to the constant level at 30 min. 4) It was observed that the lysosomal degradation was stimulated with bacterial pyrogen (LPS) at 37 degrees C but LPS did not directly affect the lysosomal fraction of PMN.


Molecular epidemiology of methicillin-resistant Staphylococcus aureus in a university hospital in northwestern Spain.
Continuous monitoring of methicillin-resistant Staphylococcus aureus (MRSA) is necessary to understand the clonal evolution of successful lineages. In this study, we identified the MRSA clones circulating in a Spanish hospital during a 2-year period, assessed their relationship with antimicrobial resistance profiles, and investigated the presence of the emerging community-associated and livestock-associated MRSA lineages (CA-MRSA, LA-MRSA). CC5-MRSA-IV isolates were the most frequently recovered, which supports the previously reported prevalence of this clone in Spanish hospitals. We observed ST125 isolates that harbored specific cassette chromosome recombinase (ccr) gene elements of the staphylococcal cassette chromosome mec (SCCmec) types IV and VI. That clone, which was first detected only recently, has increased resistance to erythromycin. Furthermore, 94% of the infections were caused by non-multiresistant isolates. Neither CA-MRSA nor LA-MRSA isolates were observed. These findings, along with related events over the last decade, suggest the establishment of a clonal endemic population in the Spanish clinical environment.


Detailed characterization of PD-1/PD-L1 and CTLA4 expression and tumor-infiltrating lymphocytes in yolk sac tumors.
Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been confirmed, and the comprehensive analysis of tumor immune microenvironment and the expression of PD-1/PD-L1 and CTLA4 were also not thoroughly evaluated. Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tumor specimens from 23 YSTs patients to detect the density and distribution of tumor-infiltrating T cells, tertiary lymphoid structures (TLSs), as well as the expression of PD-1/PD-L1 and CTLA4. Overall, more than half (61 %) of all patients exhibited an immune-desert phenotype based on CD3+ T cells. PD-1 expression was identified in five tumor samples (21.7 %), and PD-L1 expression exhibited a different positive rate in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) (39.1 % and 17.4 %). Noteworthily, the rate of positive CTLA4 expression in both TCs and TILs was markedly higher (69.6 % and 56.5 %) than those of PD-1 and PD-L1 expression. Furthermore, TLSs were observed in 21.74 % of all tissues, and samples with TLSs exhibited significantly higher densities of TILs and higher expression of immune checkpoint molecules, particularly PD-1/PD-L1. In addition, tumors located in testes also exhibited a higher density of TILs and higher expression of immune checkpoint molecules. Generally a high frequency of CTLA4 expression was found, PD-1/PD-L1 expression, the immune-inflamed phenotype, and TLSs were low frequency in YSTs, however, YSTs in testes showed a higher density of TILs and higher expression of immune checkpoint molecules.


Accumulation properties of cadmium in a selected vegetable-rotation system of southeastern China.
A rotation experiment was conducted in a greenhouse with three vegetable crops on red yellowish soil (RYS) and silt loamy soil (SLS) to study Cd accumulation in pak choi ( Brassica chinensis L.), tomato ( Lycopersicon esculentum), and radish ( Raphanus sativus L.). Critical Cd concentrations in the two soils were evaluated for these vegetables based on human dietary toxicity. Cadmium was added as Cd(NO 3) 2 at a rate of 0-7.00 mg Cd kg (-1) soil. Shoot growth was not inhibited by Cd except for radish grown on RYS. A small amount of Cd stimulated growth of the vegetables. Cadmium concentration in edible parts of the vegetables generally increased with Cd concentration in soils but was higher in RYS than SLS. The distribution of Cd in pak choi and tomato decreased in the order root > shoot > fruit, but the order was shoot > root for radish. When Cd content in the edible parts reached maximum contaminant levels for safety food standards, the soil total Cd concentrations were 0.327 and 0.120 mg kg (-1) in RYS and 0.456 and 0.368 mg kg (-1) in SLS for pak choi stem and radish, respectively, whereas ammonium acetate-extractable Cd was 0.066 and 0.089 mg kg (-1) in RYS and 0.116 and 0.092 mg kg (-1) in SLS for pak choi leaf and tomato, respectively, based on food safety standards.


Expression of p43 associated placental isoferritin (PLF) correlates inversely with cell growth in breast cancer cell lines MCF-7 and T47-D.
We have previously demonstrated that the expression of the recently described immunosuppressive antigen p43 in breast cancer patients correlates with early stages of the disease and a low degree of proliferation of the tumors. Attempts were made to evaluate the expression of p43 in two breast cancer cell lines (MCF-7 and T47-D) stimulated to proliferation by 17-beta estradiol and fetal bovine serum (FBS). p43 expression was determined by RIA technique using the new monoclonal antibody CM-H-9, the rate of proliferation was assessed by [3H]thymidine incorporation during 72 hours of incubation. Induction of proliferation by addition of 17-beta estradiol and FBS to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. The level of p43 expression in nonstimulated cells was low in comparison to that in cells cultivated routinely (15% FBS, no estrogen). However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen stimulated proliferation. Our in vitro results confirmed previous clinical observations describing an inverse correlation between p43 synthesis and degree of proliferation and differentiation in breast cancer for the first time. However, the pathologic mechanisms leading to this phenomenon need to be elucidated.


Molecular Evidence for Natural Hybridization between Cotoneaster dielsianus and C. glaucophyllus.
Hybridization accompanied by polyploidization and apomixis has been demonstrated as a driving force in the evolution and speciation of many plants. A good example to study the evolutionary process of hybridization associated with polyploidy and apomixis is the genus Cotoneaster (Rosaceae), which includes approximately 150 species, most of which are polyploid apomicts. In this study, we investigated all Cotoneaster taxa distributed in a small region of Malipo, Yunnan, China. Based on the morphological characteristics, four Cotoneaster taxa were identified and sampled: C. dielsianus, C. glaucophyllus, C. franchetii, and a putative hybrid. Flow cytometry analyses showed that C. glaucophyllus was diploid, while the other three taxa were tetraploid. A total of five low-copy nuclear genes and six chloroplast regions were sequenced to validate the status of the putative hybrid. Sequence analyses showed that C. dielsianus and C. glaucophyllus are distantly related and they could be well separated using totally 50 fixed nucleotide substitutions and four fixed indels at the 11 investigated genes. All individuals of the putative hybrid harbored identical sequences: they showed chromatogram additivity for all fixed differences between C. dielsianus and C. glaucophyllus at the five nuclear genes, and were identical with C. glaucophyllus at the six chloroplast regions. Haplotype analysis revealed that C. dielsianus possessed nine haplotypes for the 11 genes, while C. glaucophyllus had ten, and there were no shared haplotypes between the two species. The putative hybrid harbored two haplotypes for each nuclear gene: one shared with C. dielsianus and the other with C. glaucophyllus. They possessed the same chloroplast haplotype with C. glaucophyllus. Our study provided convincing evidence for natural hybridization between C. dielsianus and C. glaucophyllus, and revealed that all hybrid individuals were derivatives of one initial F1 via apomixes. C. glaucophyllus served as the maternal parent at the initial hybridization event. We proposed that anthropological disturbance provided an opportunity for hybridization between C. dielsianus and C. glaucophyllus, and a tetraploid F1 successfully bred many identical progenies via apomixis. Under this situation, species integrity could be maintained for these Cotoneaster species, but attentions should be kept for this new-born hybrid.


A critique of the decision analysis for clinically localized prostate cancer.
The question of when to choose surgery over watchful waiting for treatment of clinically localized prostate cancer is difficult. Recently, the Prostate Patient Outcomes Research Team (PORT) published a decision analysis that promoted watchful waiting as a reasonable alternative to invasive treatment for many men with localized prostatic carcinoma. Criticisms were leveled at the analysis itself, its structure, and especially the probabilities and utilities used in the model. We reexamine the PORT decision analysis. Structural sensitivity of the model was conducted, as were multi-way analyses incorporating data more recent than those used in the PORT analysis. The model structure is concluded to be sound and reasonable given the available literature on prostate cancer progression. However, recent data suggest that some probabilities used in the PORT analysis may be understated, causing life expectancy for surgical treatment to be understated. Using these recent data, the decision to operate on all grades of prostate cancer is strongly supported. This finding contradicts that of the original PORT analysis, which suggested that surgery would decrease quality-adjusted life expectancy for patients with well differentiated lesions. Ethical considerations aside, a clinical trial, such as the Prostate Cancer Intervention Versus Observation Trial, would help to establish reliable progression rates. Also, additional quality of life studies with actual prostatic cancer patients are needed for accurate decision making. Decision scientists and academic urologists should collaborate on model refinement and subsequent analyses.


Antimicrobial Resistance of Pseudomonas aeruginosa Isolated from Dogs and Cats in Primary Veterinary Hospitals in Japan.
We collected 200 Pseudomonas aeruginosa isolates from dogs and cats in primary veterinary hospitals in Japan to investigate their antimicrobial resistance. Resistance rates against ciprofloxacin, cefotaxime, gentamicin, amikacin, and fosfomycin were 9%, 12.5%, 4.5%, 2.5%, and 35.5%, respectively. One strain displayed resistance (0.5%) to ceftazidime. We did not detect any imipenem-resistant or multidrug-resistant P. aeruginosa strains as defined by the Japanese Ministry of Health, Labour, and Welfare Law Concerning the Prevention of Infections and Medical Care for Patients with Infections. In addition, we did not find any P. aeruginosa isolates that produced metallo-β-lactamase, the aminoglycoside 6'-N-acetyltransferase AAC(6')-Iae, or the aminoglycoside acetyltransferase AAC(6')-Ib.


Examination of barriers and barrier alteration in transscleral iontophoresis.
The flux enhancing mechanisms of transscleral iontophoresis are not well understood. The objective of the present study was to investigate the ocular barrier and barrier alterations in transscleral iontophoretic delivery with magnetic resonance imaging (MRI). Experiments involving constant current transscleral iontophoresis of 2 mA (current density 10 mA/cm(2)) and subconjunctival injection were conducted with rabbits in vivo and postmortem and with excised sclera in side-by-side diffusion cells in vitro. The postmortem and in vitro experiments were expected to be helpful in clarifying the importance of vascular clearance and other transport barriers in transscleral iontophoresis. Manganese ion (Mn(2+)) and manganese ethylenediaminetetraacetic acid complex (MnEDTA(2-)) were the model permeants. The results show that pretreatment of the eye with an electric field by iontophoresis enhanced subconjunctival delivery of the permeants to the anterior segment of the eye in vivo. This suggests that electric field-induced barrier alterations can be an important absorption enhancing mechanism of ocular iontophoresis. Penetration enhancement was magnified in the postmortem experiments with larger amounts of the permeants delivered into the eye and to the back of the eye. The different results observed in the in vivo and postmortem studies can be attributed to ocular clearance in ocular delivery.


Temporal-spatial analysis of an age-space structured foot-and-mouth disease model with Dirichlet boundary condition.
Foot-and-mouth disease is a highly contagious and economically devastating disease of cloven-hoofed animals. The historic occurrences of foot-and-mouth diseases led to huge economic losses and seriously threatened the livestock food security. In this paper, a novel age-space diffusive foot-and-mouth disease model with a Dirichlet boundary condition, coupling the virus-to-animals and animals-to-animals transmission routes, has been proposed. The basic reproduction number R0 is defined as the spectral radius of a next generation operator K, which is calculated in an explicit form, and it serves as a vital value determining whether or not the disease persists. The existence of a unique trivial nonconstant steady state and at least one nonconstant endemic steady state of the system is established by a smart Lyapunov functional and the Kronoselskii fixed point theorem. An application to a foot-and-mouth outbreak in China is presented. The findings suggest that increasing the movements and disinfection of the environment for animals apparently reduce the risk of a foot-and-mouth infection.


Effect of 2,4-Diacetylphloroglucinol Producing, Overproducing, and Nonproducing Pseudomonas fluorescens F113 in the Rhizosphere of Pea.
Pseudomonas fluorescens F113lacZY and modified strains carrying different function modifications were assessed for their impact in the rhizosphere of pea. Strain F113lacZY naturally produces the anti-fungal metabolite 2,4-diacetylphloroglucinol (Phl) useful in plant disease control. The first modified strain of F113 was repressed in production of Phl, creating the Phl negative strain F113G22. The second was a plasmid based overproducer of Phl (F113Rif (pCUGP)). Both the F113lacZY and the F113Rif (pCUGP) strains increased the rhizoplane fungal populations, whereas the same strains reduced the rhizosphere soil fungal populations with respect to the control. Similar results were found with the rhizoplane and rhizosphere soil bacterial populations. The F113G22 treatment resulted in a significantly greater indigenous fluorescent Pseudomonas population than the F113lacZY and F113Rif (pCUGP) treatments and a greater total Pseudomonas population than the control, F113lacZY, and F113Rif (pCUGP) treatments. Overproduction of Phl did not affect the establishment of the introduced Pseudomonas population. None of the inocula displaced the indigenous populations, but the F113G22 inocula had an additive effect on the total Pseudomonas population. P (phosphatase), S (sulphatase), and N (urease) cycle enzyme activities were increased while C (glucosidase, NAGase) cycle activities were decreased by the F113lacZY and F113Rif (pCUGP) treatments, suggesting C leakage from the roots. Overall, most effects of inoculation compared to the wild type were found with the non-Phl-producing strain. Overproduction of Phl had little environmental effect in relation to wild-type inocula.


Peroxisome proliferator-activated receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma.
Asthma is characterized by a predominant T(H)2 type immune response to airborne allergens. Controlling T(H)2 cell function has been proposed as therapy for this disease. We show here that ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)gamma significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease. A PPARgamma ligand, 15-deoxy-delta(12,14)-prostaglandin J(2), significantly inhibited production of the T(H)2 type cytokine IL-5 from T cells activated in vitro. More importantly, in a murine model of allergic asthma, mice treated orally with ciglitazone, a potent synthetic PPARgamma ligand, had significantly reduced lung inflammation and mucous production following induction of allergic asthma. T cells from these ciglitazone treated mice also produced less IFNgamma, IL-4, and IL-2 upon rechallenge in vitro with the model allergen. Our results suggest that ligands for PPARgamma may be effective treatments for asthmatic patients.


An Unobtrusive Computerized Assessment Framework for Unilateral Peripheral Facial Paralysis.
Unilateral peripheral facial paralysis (UPFP) is a form of facial nerve paralysis and clinically classified according to conditions of facial symmetry. Prompt and precise assessment is crucial to neural rehabilitation of UPFP. The prevalent House-Brackmann (HB) grading system relies on subjective judgments with significant interobservation variation. Therefore, to explore an objective method for the UPFP assessment, clinical image sequences are captured using a web camera setup while 5 healthy and 27 UPFP subjects perform a group of predefined actions, including keeping expressionless, raising brows, closing eyes, bulging cheek, and showing teeth in turn. First, facial region is decided using Haar cascade classifier, and then landmark points are acquired by a supervised descent method. Second, these landmark points are used to generate a group of features reflecting the structural parameters of regions of eyebrows, eyes, nose, and mouth, respectively. Third, correlation coefficients are computed between the raw features HB scores. To reduce feature dimensions, only those with correlation coefficients larger than an empirically selected value, 0.35, are input into a support vector machine to generate a classifier. With the classifier, exact match (discrepancy = 0 between result from proposed method and HB scores) rate at 49.9%, and loose match (discrepancy = 1) rate at 87.97% are achieved on the experiment data. After sample augmentation, the final rate is increased to 90.01%, outperformed previous reports. In conclusion, it is demonstrated with an unobtrusive web camera setup, encouraging results have been generated with the proposed framework in this exploratory study.


Lung volume reduction surgery in Australia and New Zealand. Six years on: registry report.
Lung volume reduction surgery (LVRS) has been shown to improve lung function, exercise performance, and quality of life in highly selected individuals with severe emphysema; however, major questions regarding the efficacy and long-term outcomes of LVRS still remain unanswered. Pending the results of large randomized controlled trials (RCTs), the Australian and New Zealand LVRS Database was created to audit local clinical practice and patient outcomes. To review patient selection, surgical activity, and patient outcomes related to LVRS in Australia and New Zealand. Prospective data were voluntarily submitted by hospitals performing LVRS in Australia and New Zealand. Preoperative, surgical, perioperative, and follow-up variables were analyzed. Data were collected from 15 hospitals regarding 529 patients. Mean age (+/- SD) at surgery was 63 +/- 7 years. Preoperatively, FEV(1) was 29 +/- 9% predicted, total lung capacity (TLC) was 138 +/- 20% predicted, residual volume (RV) was 250 +/- 64% predicted, and 6-min walk (6MW) distance was 327 +/- 111 m. There has been a reduction in the overall number of cases and hospitals performing LVRS since 1999. Improvements in lung function following LVRS (ie, FEV(1) increase of 38%, RV decrease of 27%, TLC decrease of 17%) and exercise capacity (ie, 6MW distance increase of 24%) appear to be maintained for approximately 3 years. LVRS continues to be performed in Australia and New Zealand, predominantly in large tertiary teaching hospitals with similar outcomes to those described in the literature. It remains difficult to capture long-term lung function and survival outcomes in this population. Ongoing audit and RCTs are both required to resolve the confusion that still shrouds this procedure.


Endocytosis of antigen, anti-idiotype, and anti-immunoglobulin antibodies and receptor re-expression by murine B cells.
The endocytosis of Ag mediated by membrane-associated Ig (mIg) molecules has been spectrophotometrically monitored using a cell line (2C3) specific for the hapten phthalate (Xmp) and employing conjugates of Xmp and horseradish peroxidase (HRP) as the labeled ligand. Approximately 50% of both Xmp-HRP, or the larger ligand, Xmp-keyhole limpet hemocyanin-HRP, are internalized rapidly, reaching an initial plateau by 30 min. The rate of endocytosis of anti-idiotype-HRP is similar to the rates that were observed for the hapten-bearing ligands, while a slower rate of endocytosis of anti-Ig-HRP was observed. The percent of ligand bound that is internalized and the rate of endocytosis appear to be largely independent of the size and amount of ligand bound per cell. However, mIg-mediated endocytosis is markedly reduced when mIg-ligand complexes are more extensively cross-linked by the binding of a second antibody. In addition to the initial rapid phase of endocytosis, there is a prolonged phase during which more of the bound ligand is internalized, and up to 90% of the internalized ligand is degraded. Re-expression of Ag-binding receptors by the 2C3 cells is independent of new protein synthesis and is accomplished in part by the translocation of a presynthesized pool of mIg molecules from the cytoplasm to the plasma membrane of the cell. The kinetics of endocytosis of HRP-labeled anti-Ig antibodies by BALB/c splenic B-lymphocytes and other B-lymphocyte cell lines is very similar to the endocytosis of Ag and anti-idiotype observed with the 2C3 cell line. Light and electron microscopy are also performed to visually confirm that the HRP-labeled ligands are being internalized and to determine the percentage of cells involved in this process. Finally it was determined that the transmembrane and cytoplasmic domains of the mIg molecules are required for endocytosis since the secreted form of the molecule (which lacks these domains) fails to mediate the internalization of bound ligand.


A versatile papaya mosaic virus (PapMV) vaccine platform based on sortase-mediated antigen coupling.
Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide. This represents a serious limitation to the utility of this approach as fusion of small peptides only is tolerated. We have developed a novel approach in which peptides are fused directly to pre-formed PapMV nanoparticles. This approach is based on the use of a bacterial transpeptidase (sortase A; SrtA) that can attach the peptide directly to the nanoparticle. An engineered PapMV CP harbouring the SrtA recognition motif allows efficient coupling. To refine our engineering, and to predict the efficacy of coupling with SrtA, we modeled the PapMV structure based on the known structure of PapMV CP and on recent reports revealing the structure of two closely related potexviruses: pepino mosaic virus (PepMV) and bamboo mosaic virus (BaMV). We show that SrtA can allow the attachment of long peptides [Influenza M2e peptide (26 amino acids) and the HIV-1 T20 peptide (39 amino acids)] to PapMV nanoparticles. Consistent with our PapMV structural model, we show that around 30% of PapMV CP subunits in each nanoparticle can be fused to the peptide antigen. As predicted, engineered nanoparticles were capable of inducing a strong antibody response to the fused antigen. Finally, in a challenge study with influenza virus, we show that mice vaccinated with PapMV-M2e are protected from infection. This technology will allow the development of vaccines harbouring long peptides containing several B and/or T cell epitopes that can contribute to a broad and robust protection from infection. The design can be fast, versatile and can be adapted to the development of vaccines for many infectious diseases as well as cancer vaccines.


Assessment of dynamic balancing responses following perturbations during slow walking in relation to clinical outcome measures for high-functioning post-stroke subjects.
Generating appropriate balancing reactions in response to unexpected loss of balance during walking is important to prevent falls. The purpose of this study was to assess dynamic balancing responses following pushes to the pelvis in groups of post-stroke and healthy subjects. Forty-one post-stroke subjects and forty-three healthy subjects participated in the study. Dynamic balancing responses to perturbations triggered at heel strike of the left or right leg, directed in the forward, backward, inward and outward directions during slow treadmill walking were assessed. Responses of the healthy group provided reference values used to classify responses of the post-stroke group into two subgroups; one within the reference responses ("inside" subgroup) and the other that falls out ("outside" subgroup). A battery of selected clinical outcome measures (6-Minute Walk Test, 10-Meter Walk Test, Timed-Up-and-Go test, Four Square Step Test, Functional Gait Assessment, Functional Independence Measure and One-legged stance test) was additionally assessed in the post-stroke group. The "inside" subgroup of post-stroke subjects was able to appropriately modulate centre-of-pressure and ground-reaction-force both under the impaired and non-impaired leg in response to perturbations. The "outside" subgroup of post-stroke subjects showed limited modulation of centre-of-pressure and ground-reaction-force under the impaired leg; instead stepping strategy was used in which the non-impaired leg was placed such as to make a longer step (forward perturbation), to make a shorter step (backward perturbation) or to make a cross-step (outward perturbation). Consequently, peak centre-of-mass displacements following perturbations were significantly higher in the "outside" subgroup compared to the "inside" subgroup. Responses in both subgroups following inward perturbations did not differ. Majority of clinical outcome measures moderately correlated with the peak centre-of-mass displacements for forward perturbations and exhibited weak correlations for other perturbation directions. Substantial number of post-stroke subjects, that were considered to be independent walkers, have reduced capabilities to execute appropriate balancing responses following perturbations commencing on the hemiparetic leg and may thus benefit from perturbation-based training. Timed-Up-and-Go and Functional Independence Measure tests may provide an indication on the abilities of each subject to counteract unexpected loss of balance. However, a reliable assessment should be done through perturbation-based measures.


Use of cilostazol in percutaneous coronary interventions.
To evaluate the addition of cilostazol to standard dual antiplatelet therapy (DAT) with aspirin and clopidogrel in patients receiving coronary stenting. Relevant information was identified through a search of MEDLINE (1966-November 2011), International Pharmaceutical Abstracts (1960-2011), and Cochrane Databases (publications archived until November 2011) using the terms cilostazol, percutaneous coronary intervention, triple therapy, and antiplatelet agents. English-language prospective and retrospective studies, including registry data in adults, were eligible for inclusion if triple therapy with cilostazol was compared with DAT with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) with stenting. Article bibliographies were also reviewed. Cilostazol uniquely possesses antiproliferative properties in addition to its antiplatelet effects. Several prospective and retrospective clinical trials evaluated it as a third agent in standard antiplatelet regimens after PCI with both bare metal and drug-eluting stents. Both angiographic and clinical outcomes, including major adverse cardiac events (MACEs), have been improved with the addition of cilostazol to DAT in most trials, without increasing bleeding risk. Higher-risk patients, such as elderly individuals and patients with diabetes, long lesions, or small vessels, seem to benefit the most from triple therapy. Patients who are poor responders to clopidogrel also appear to benefit from the addition of cilostazol by improving platelet reactivity with standard DAT. Triple therapy with cilostazol has been shown to reduce MACEs by providing increased inhibition of platelet aggregation and reducing the rates of in-stent thrombosis compared to DAT without increasing the risk of bleeding complications. Further studies are needed to identify proper patient selection based on risk factors for the addition of cilostazol. Additionally, studies comparing cilostazol with newer antiplatelet therapies, such as prasugrel and ticagrelor, are needed.


Plasma cholesterol levels and short-term adaptations of metabolism and milk production during feed restriction in early lactating dairy cows on pasture.
Low plasma total cholesterol (TC) concentrations are characteristic during the negative energy balance in early lactating dairy cows. The objective was to investigate short-term effects of different TC concentrations during an aggravated energy deficiency through a 1-week concentrate withdrawal on adaptations of metabolism and milk production. Multiparous Holstein cows (n = 15) were investigated during 3 week beginning at 24 ± 7 DIM (mean ± SD). Cows were kept on pasture and received additional concentrate in experimental week 1 and 3, while in week 2, concentrate was withdrawn. Blood was sampled once and milk twice daily. Based on their average TC concentration during week 1 (prior to concentrate withdrawal), cows were retrospectively assigned into a high (H-Chol; n = 8, TC ≥ 3.36 mmol/L) and a low TC groups (L-Chol; n = 7, TC < 3.36 mmol/L). Concentrations of phospholipids and lipoproteins were higher in H-Chol compared to L-Chol throughout the study (p < 0.05). During concentrate withdrawal, milk yield, glucose and insulin concentrations decreased similarly in both groups, while milk fat, milk acetone and plasma BHB were higher in H-Chol compared to L-Chol (p < 0.05). Compared to initial values, plasma NEFA, TAG and VLDL increased in both groups within 2 days after concentrate withdrawal (p < 0.05). Concentrations of NEFA during week 2 were greater in L-Chol compared to H-Chol (p < 0.05). Despite reintroduction of concentrate, milk yield in H-Chol remained lower for two more days compared to week 1 (p < .05), whereas milk yield recovered immediately in L-Chol. Activity of aspartate aminotransferase was higher in H-Chol compared to L-Chol in week 2 (p < 0.05). Greater plasma TC concentrations were associated with a reduced increase of NEFA. Further research is warranted if TC concentrations are related to adipose tissue mobilization and fatty acid turnover.


The changing health care environment: implications for residency training.
Throughout the United States, the growth of managed care is forcing pediatric providers (physicians and hospitals) to reconstruct and integrate the health care delivery system with a focus away from the academic center and toward the community. Managed care also is forcing new financing approaches geared toward the assumption of economic risk for patient management and utilization of services. Radical changes in pediatric training programs will be necessary to accommodate the strategic and operational changes being pursued in response to these evolving market forces. These changes, while disruptive, will strengthen the breadth and diversity of graduate medical education and will better prepare trainees for the new delivery system in which they will practice. In this article, we examine how the evolution of managed care is redefining the basic financial and organizational framework for pediatric care and the implications of this redefinition for children's hospitals and academic medical center-based pediatric programs. We draw on our experience in the greater Philadelphia market to illustrate the impact of these changes and discuss one pediatric system's response. Finally, we review the educational opportunities provided by these changes.


Isotopic niche provides an insight into the ecology of a symbiont during its geographic expansion.
The study of the recent colonization of a symbiont and its interaction with host communities in new locations is an opportunity to understand how they interact. The use of isotopic ratios in trophic ecology can provide measurements of a species' isotopic niche, as well as knowledge about how the isotopic niches between symbiont and host species overlap. Stable isotope measurements were used to assess the sources of carbon assimilated by the host species (the bivalves Mytilus galloprovincialis and Scrobicularia plana) and their associated symbiont pea crab Afropinnotheres monodi, which occurs within these bivalves' mantle cavities. The mixing model estimates suggest that all of them assimilate carbon from similar sources, particularly from pseudofaeces and particulate organic matter in this symbiotic system based on filter feeding. The symbiotic species occupy comparable trophic levels and its association seems to be commensal or parasitic depending on the duration of such association. The pea crab A. monodi reflects a sex-specific diet, where males are more generalist than the soft females because the latter's habitat is restricted to the host bivalve. The high isotopic overlap between soft females and M. galloprovincialis may reflect a good commensal relationship with the host.


Oxidative tissue response promoted by 5-aminolevulinic acid promptly induces the increase of plasma antioxidant capacity.
The heme precursor 5-aminolevulinic acid (ALA), acting as a prooxidant, has been proposed to underlie the clinical manifestations of various porphyric disorders. Accordingly, ALA-generated oxyradicals where shown to cause oxidative lesions in biomolecules and isolated cell organelles and to release iron from ferritin. In rats, administered ALA triggered oxidative stress in liver, brain and red muscles. We now study the correlation between the plasma antioxidant capacity and tissue oxidative damage, after acute (one and two doses) and prolonged (eight doses) ALA treatment of rats (one dose of ALA = 40 mg/kg body weight). The in situ spontaneous chemiluminescence intensity increased 5-fold in brain, 50% in liver and 4-fold in soleus muscle upon two dose-treatment, indicating tissue response to oxidative injury by ALA. Chemiluminescence reached the highest intensity after one or two doses of ALA and decreased after eight doses in all tissues. The plasma trapping capacity, evaluated by the luminol/2-amidinopropane system, gave a parallel response: maximum values after two doses and decreased values after prolonged treatment. After eight doses, the ALA concentration was found to be 3-fold above the normal value in plasma, 48% higher in liver and 38% higher in total brain. These data indicate that the plasma antioxidant system responds to ALA treatment and is correlated with tissue chemiluminescence. In vitro studies showed that ALA does not interfere with the antioxidant plasma capacity, neither promoting oxidation of plasma elements nor binding to plasma proteins.


Dietary Exogenous α-Amylase Modulates the Nutrient Digestibility, Digestive Enzyme Activity, Growth-Related Gene Expression, and Diet Degradation Rate of Olive Flounder (Paralichthys olivaceus).
In this study, a 12-week feeding experiment was conducted to characterize the effects of exogenous α-amylase on the growth, feed utilization, digestibility, plasma α-amylase activity, feed degradation rate, and fecal particle size of olive flounder (Paralichthys olivaceus). Diet was supplemented with 0 (AA0; control), 100 (AA100), 200 (AA200), or 400 (AA400) mg/kg of α-amylase, respectively. Fish (273.1 ± 2.3 g) were stocked into 12 tanks (25 fish/1,000-L tank) and 3 tanks were randomly selected for each diet group. As a result, α-amylase was found to have no significant effects (p ≥ 0.05) on the growth, feed utilization parameters, and whole-body proximate compositions. α-Amylase-treated fish exhibited only a significant increase in the apparent digestibility coefficient of carbohydrates compared to the controls. In addition, in vitro analyses revealed that α-amylase dose-dependently increased (p < 0.05) the feed degradation rate, while photographs of the intestinal content after 2, 4, and 8 h of feeding demonstrated an improved degradation rate in the α-amylase-treated groups. Plasma α-amylase content was higher in the AA200 and AA400 groups, whereas the control group produced significantly larger-sized fecal particles (90% size class) than these two groups. In the intestine, no changes were observed in the expression levels of the immune-related TNF-α, IL-1β, IL-2, immunoglobulin-M, HSP-70, lysozyme, and amylase alpha-2A. However, growth-related genes IGF-1, IGF-2, TGF-β3, and growth hormone genes were upregulated in muscle tissues. Collectively, exogenous α-amylase has positive roles in the modulation of the digestibility coefficient, blood α-amylase concentration, growth-related gene expression, and diet degradation for improved digestion in olive flounder.


Selective product amplification of thymine photodimer by recognition-directed supramolecular assistance.
Two symmetric ditopic supramolecular templates (1 and 2) each presenting two hydrogen bonding recognition subunits were synthesized. Each such subunit comprises the same donor and acceptor pattern, capable of binding a substrate molecule with complementary hydrogen bonding groups to form a supramolecular complex. Substrate molecules, such as thymine or uracil derivatives, yield 2 : 1 complexes with the acceptors involving two hydrogen bonds to each subunit with ideal orientation for subsequent [2 + 2] dimerization upon photoirradiation. Selective syn photoproduct formation and concomitant suppression of the trans isomer are favored by orientation of the two guest nucleobases within the template cleft. Complementary donor and acceptor hydrogen bonding induced positioning of the two substrates and steric hindrance within the template clefts are responsible for the selective product formation.


Reaction between CH2 and HCCN: a theoretical approach to acrylonitrile formation in the interstellar medium.
Acrylonitrile (CH2CHCN) was first detected in dense molecular cloud SgrB2. The synthesis of this interstellar molecule is reported to be quite difficult. Therefore, in the present work an attempt has been made to explore the possibility of formation of acrylonitrile from some simple molecules and radicals detected in interstellar space by radical-radical interaction scheme, both in the gas phase and in the icy grains. All calculations are performed using quantum chemical methods with density functional theory (DFT) at the B3LYP/6-311G (d,p) level and Møller-Plesset perturbation theory at the MP2/6-311G (d,p) level. In the discussed chemical pathway, the reaction is found to be totally exothermic and barrier less giving rise to a high probability of acrylonitrile formation in Interstellar space.


Measuring nurses' time in medication related tasks prior to the implementation of an electronic medication management system.
A substantial proportion of nurses' work consists of medication related tasks undertaken in a current environment of high medication error rates. Electronic medication management systems (EMMS) are anticipated to address many of the factors which contribute to errors. These factors, for example illegible hand-written drug orders, reputedly require nurses to spend additional time in clarification and discussion. We report an observational modified time and motion study of 44 registered nurses (215 hours of observation) in a major academic hospital to quantify the time nurses spend in medication related tasks prior to EMMS introduction. On average nurses spent seven minutes in an 8.75 hour shift clarifying or discussing medication issues. The majority of this time (5.4 mins) was spent talking with other nurses. Only 1.6 minutes was spent clarifying or discussing medication with doctors. Our results call into question some of the predicted efficiency benefits to nurses' work following EMMS introduction.


Individual Choice and Risk: The Case of Higher Education.
The expansion of higher education raises the risk environment for school-leavers as more occupations become partially graduate with the result that occupational signals are fuzzy. This makes the educational decision more difficult and more risky, especially with more of the cost of higher education being transferred to the individual. After a discussion of the nature of risk, derived from Beck, and of the role of government policy and of economics in obscuring this, the analysis uses simple quantitative techniques, based on British Labour Force Survey data, to demonstrate the increased fuzziness of graduate work. It is also shown that a rising proportion of graduates receive only average pay, thus raising the risks associated with educational investments even further.


Characterization and production of protein complexes by co-expression in Escherichia coli.
The functional units within cells are often macromolecular complexes rather than single species. Production of these complexes as assembled homogenous samples is a prerequisite for their biophysical and structural characterization and hence an understanding of their function in molecular terms. Co-expression in Escherichia coli has been used routinely to decipher the subunit composition, assembly, and production of whole protein complexes. Such complexes can then be used to reconstitute protein/nucleic acid complexes in vitro. In this chapter we present protocols for the widely utilized ACEMBL and pET-MCN/pET-MCP vector series which enable the rapid and automated co-expression of protein complexes in Escherichia coli.


Cognitive flexibility in a Tanganyikan bower-building cichlid, Aulonocranus dewindti.
Cognitive flexibility, the ability to modify one's decision rules to adapt to a new situation, has been extensively studied in many species. In fish, though, data on cognitive flexibility are scarce, especially in the wild. We studied a lekking species of cichlid fish in Lake Tanganyika, Aulonocranus dewindti. Males create sand bowers as spawning sites and maintain them by removing any objects falling into it. In the first part of our experiment, we investigated the existence of spontaneous decision rules for the maintenance of the bowers. We showed that if a snail shell and a stone are placed in their bower, fish prefer to remove the shell first. In the second phase of our experiment, we took advantage of this spontaneous decision rule to investigate whether this rule was flexible. We tested five individuals in a choice against preference task, in which the fish had to modify their preference rule and remove the stone first to be allowed to then remove the shell and have a clean bower. While there was no overall trend towards flexibility in this task, there was variation at an individual level. Some individuals increased their preference for removing the shell first, deciding quickly and with little exploration of the objects. Others were more successful at choosing against preference and showed behaviours suggesting self-regulatory inhibition abilities. Bower-building cichlids could therefore be a promising model to study cognitive flexibility, and other aspects of animal cognition in the wild.


Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.
Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients.


Lipopolysaccharide Upregulated Intestinal Epithelial Cell Expression of Fn14 and Activation of Fn14 Signaling Amplify Intestinal TLR4-Mediated Inflammation.
TLR4 in intestinal epithelial cells has been shown both inflammatory and homeostatic roles following binding of its cognate ligand lipopolysaccharide (LPS). TWEAK-Fn14 axis plays an important role in pathologies caused by excessive or abnormal inflammatory responses. This study aimed to evaluate potential cross-talk between TLR4 and TWEAK/Fn14 system in porcine small intestinal epithelial cells. Our in vivo results showed that, compared with the age-matched normal control piglets, increased expression of Fn14 in epithelium and decreased TWEAK expression in lamina propria were detected in the small intestinal of piglets stimulated with LPS. Consistent with this finding, treatment with LPS increased the expression of Fn14 and TLR4 while decreased TWEAK expression in porcine small intestinal epithelial cell lines SIEC02. Interestingly, modulating Fn14 activation using agonistic anti-Fn14 decreased TLR4-mediated TNF-α production by SIEC02. In addition, pretreatment of LPS-stimulated SIEC02 with recombinant TWEAK protein suppresses the expression of Fn14 and TNF-α and inhibits the negative impact of LPS on the tight junctional protein occludin expression. In conclusion, this study demonstrates that the TWEAK-independent Fn14 activation augments TLR4-mediated inflammatory responses in the intestine of piglets. Furthermore, the TWEAK-dependent suppression of Fn14 signaling may play a role in intestinal homeostasis.


Tolerance versus immune response -- microRNAs as important elements in the regulation of the HLA-G gene expression.
HLA-G is a class Ib HLA which has gained much attention due to its multiple functions on the immune system. HLA-G exerts several immunomodulatory effects, being beneficially implicated in embryo implantation and fetal survival but, conversely, being potentially detrimental in tumors and viral infections. Such a two-edged sword behavior suggest that HLA-G expression is under tight regulation. However, to date, little is known about the regulation of this gene and previous works have been unable to well correlate HLA-G regulation at the mRNA level with the polymorphic variants at the genomic level. Here we present the hypothesis that an element, which was until now neglected, might play a role in HLA-G expression regulation: MicroRNAs might participate in the regulation of the HLA-G gene expression through a putative microRNA binding site at its 3' UTR region. Inside the 20 nt region of this microRNA binding site lies a C/G polymorphism, which was shown to be responsible for differential microRNA binding affinity and translation suppression. The role of microRNA binding on the regulation of HLA-G gene expression (and therefore on tolerance versus immune response) can be easily tested through relatively simple steps: Confirming the expression of those three complementary microRNAs in human cells which express HLA-G, followed by examination of the correlation between HLA-G mRNA and protein production controlling for HLA-G genotypes and microRNA levels; finally, selective inhibition of microRNA activity with anti-sense oligos restoring HLA-G production would access microRNA influence on HLA-G expression which, if confirmed, might help in the development of strategies to the management of several conditions in which HLA-G is involved, including pregnancy complications, transplantation, and cancer.


Selective inhibition of glycoprotein-processing enzymes. Differential inhibition of glucosidases I and II in cell culture.
In this study, we compared the effects of 2,6-dideoxy-2,6-imino-7-O-(beta-D-glucopyranosyl)-D-glycero-L-gulohep titol (MDL) to those of the glucosidase I inhibitor, castanospermine, on the purified processing enzymes glucosidases I and II. WE also compared the effects of these two inhibitors on glycoprotein processing in cell culture using influenza virus-infected Madin-Darby canine kidney cells as a model system. With the purified processing enzymes, castanospermine was a better inhibitor of glucosidase I than of glucosidase II, whereas MDL is more effective against glucosidase II than glucosidase I. In cell culture at the appropriate dose, MDL also preferentially affected glucosidase II. Thus, at 250 micrograms/ml MDL, the major [3H]glucose-labeled (or [3H]mannose-labeled) glycopeptide from the viral hemagglutinin was susceptible to endoglucosaminidase H, and the oligosaccharide liberated by this treatment was characterized as a Glc2Man7-9GlcNAc on the basis of size, resistance to digestion by glucosidase I (but sensitivity to glucosidase II), methylation analysis, and Smith degradation studies. These data indicate that at appropriate concentrations of MDL (250 micrograms/ml), one can selectively inhibit glucosidase II in Madin-Darby canine kidney cells. However, at higher concentrations of inhibitor (500 micrograms/ml), both enzymes are apparently affected. Since MDL did not greatly inhibit the synthesis of lipid-linked saccharides or the synthesis of protein or RNA, it should be a useful tool for studies on the biosynthesis and role of N-linked oligosaccharides in glycoprotein function.


Comparing quantitative values of two generations of laser-assisted indocyanine green dye angiography systems: can we predict necrosis?
Several devices exist today to assist the intraoperative determination of skin flap perfusion. Laser-Assisted Indocyanine Green Dye Angiography (LAICGA) has been shown to accurately predict mastectomy skin flap necrosis using quantitative perfusion values. The laser properties of the latest LAICGA device (SPY Elite) differ significantly from its predecessor system (SPY 2001), preventing direct translation of previous published data. The purpose of this study was to establish a mathematical relationship of perfusion values between these 2 devices. Breast reconstruction patients were prospectively enrolled into a clinical trial where skin flap evaluation and excision was based on quantitative SPY Q values previously established in the literature. Initial study patients underwent mastectomy skin flap evaluation using both SPY systems simultaneously. Absolute perfusion unit (APU) values at identical locations on the breast were then compared graphically. 210 data points were identified on the same patients (n = 4) using both SPY systems. A linear relationship (y = 2.9883x + 12.726) was identified with a high level or correlation (R(2) = 0.744). Previously published values using SPY 2001 (APU 3.7) provided a value of 23.8 APU on the SPY Elite. In addition, postoperative necrosis in these patients correlated to regions of skin identified with the SPY Elite with APU less than 23.8. Intraoperative comparison of LAICGA systems has provided direct correlation of perfusion values predictive of necrosis that were previously established in the literature. An APU value of 3.7 from the SPY 2001 correlates to a SPY Elite APU value of 23.8.


Is greener better? Associations between greenness and birth outcomes in both urban and non-urban settings.
Beneficial effects of greenness on birth outcomes have been reported, but few studies have investigated the associations in both urban and non-urban settings. We aimed to evaluate and compare linear and nonlinear associations between greenness and birth outcomes in urban and non-urban settings. From October 2015 to December 2018, participants were recruited into the Maoming Birth Cohort Study. A total of 11 258 live birth records were obtained. Greenness exposure was assessed using the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). Linear regression and nonlinear restricted cubic spline models were implemented to investigate the associations between greenness and birthweight, birth length, gestational age, preterm birth, low birthweight, small for gestational age and the potential for effect variation under urban or non-urban settings, after adjusting for covariates. A 0.1-unit increase in NDVI-500m was significantly associated with an increase of 35.4 g in birthweight [95% confidence interval (CI): 13.2, 57.7], 0.15 cm in birth length (95% CI: 0.03, 0.26), 0.88 days in gestational age (95% CI: 0.05, 1.71) and lower odds of low birthweight [odds ratio (OR) = 0.69, 95% CI: 0.56, 0.85] and preterm birth (OR = 0.70, 95% CI: 0.58, 0.85). No association with head circumference was observed. For all outcomes, no significant linear associations were observed among non-urban dwellers. Inversed 'U-shaped' associations between greenness exposure and birth outcomes were observed in the total study population. Greenness exposure was associated with increased gestational age, birthweight and birth length in urban dwellers. Nonlinear associations assessed by restricted cubic splines suggested that health benefits could be larger when increasing greenness levels from low to medium compared with increasing greenness from medium to high levels. Further studies adopting nonlinear methods are warranted to verify our findings.


The appearance of the feet in Pfeiffer syndrome caused by FGFR1 P252R mutation.
Patients affected by Pfeiffer syndrome generally present with syndromic craniosynostosis and typical limb defects including broad thumbs, wide halluces with varus deformity, toe syndactyly and sometimes elbow ankylosis. This autosomal dominant condition can be caused by mutations in either fibroblast growth factor receptor gene type 1 or 2 (FGFR1 or FGFR2). We report four new affected families showing an FGFR1 P252R mutation and emphasize the characteristic malformations of the feet in this form of Pfeiffer syndrome. In one family this was the only abnormality.


Topical non-iontophoretic application of acetylcholine and nitroglycerin via a translucent patch: a new means for assessing microvascular reactivity.
Assessments of endothelial cell function with acetylcholine have typically used systemic, regional intra-arterial, or iontophoretic delivery of drug. Each of these techniques induces systemic and/or local changes that compromise their safety or effectiveness. Using translucent drug preparations applied under laser Doppler flowmetry (LDF) probes, we tested whether local vasodilation can be induced with non-iontophoretic transdermal delivery of acetylcholine and how such dilation would compare to the dilation achieved with topical nitroglycerin in healthy volunteers. Ten subjects without known vascular disease were recruited for LDF monitoring at sites of drug application for this preliminary investigation. Topical acetylcholine chloride, nitroglycerin, and placebo were applied via translucent patches to the forehead directly below LDF probes. LDF readings increased by 406 percent (245 percent to 566 percent) and 36 percent (26 percent to 46 percent), respectively, at the acetylcholine and placebo sites (p = .005 by Wilcoxon Signed Rank Test (WSRT) for acetylcholine vs. placebo); and they increased by 365 percent (179 percent to 550 percent) at the nitroglycerin site (p = .005 by WSRT for nitroglycerin vs. placebo; p = .6 vs. acetylcholine). Transdermal delivery of acetylcholine can induce significant local vasodilatory responses comparable to those achieved with nitroglycerin without requiring iontophoresis. The means of transdermal delivery and monitoring described herein may constitute a new minimally invasive way to interrogate the microvasculature and thereby assess the microcirculatory changes induced by various disorders and therapeutic interventions.


Anti-inflammatory and immunomodulatory effects of Biodentine on human periapical lesion cells in culture.
To evaluate the effect of Biodentine eluate on cytotoxicity and production of pro- and anti-inflammatory cytokines and osteodestructive/osteoprotective cytokines in cultures of human periapical lesion cells. Conditioned Biodentine Medium (CBM) was prepared according to ISO 10993-12, by incubating Biodentine in RPMI medium (0.2 g mL-1 ) for 3 days at 37 °C. CBM contained both released microparticles and leachable soluble components. Inflammatory cells were isolated from 22 human periapical lesions after apicectomy or tooth extraction, by collagenase/DNase digestion, and cultured in several dilutions of CBM. The composition of periapical lesion cells was determined by morphological criteria, cytotoxicity was quantified by MTT and flow cytometric apoptosis/necrosis assays, whereas the levels of produced cytokines in cell culture supernatants were measured by flow cytometry and ELISA. Student t-test and Friedman test with Dunn's post-test were used for comparison of parametric and nonparametric variables, respectively. Undiluted (100%), 75% and 50% CBM were cytotoxic for periapical lesion cells due to induction of both necrosis (100% CBM) and apoptosis (75% and 50% CBM). Noncytotoxic concentrations of CBM (25%) inhibited the production of pro-inflammatory cytokines: TNF-α, (P < 0.005); IL-1β (P < 0.01); IL-6 (P < 0.005) and chemokines IL-8: (P < 0.005); MCP-1 (P < 0.005), stimulated the production of anti-inflammatory cytokine (IL-10; P < 0.005), Th2 cytokines: IL-4, IL-5 and IL-33 (all P < 0.01), and IL-17A (P < 0.01). The concentration of CBM (12.5%) inhibited the production of IL-6 (P < 0.05), IL-8 (P < 0.01) and MCP-1 (P < 0.005) and augmented the production of IL-10 (P < 0.05). No significant effects on Th1-related cytokines (IFN-γ and IL-12) and IL-23 were detected with 25% and 12.5% CBM concentrations. Both CBM concentrations inhibited the production of osteolytic receptor activator of nuclear factor kappa-Β ligand (RANKL), dose dependently (P < 0.005 and P < 0.01, respectively). Higher CBM concentrations decreased RANKL/osteoprotegerin (OPG) ratio (P < 0.05), without significant influence on the levels of osteoprotective OPG. Biodentine possesses immunomodulatory properties by suppressing pro-inflammatory and augmenting anti-inflammatory cytokines. Together with the reduction of osteodestructive mediators, this novel root-end filling cement could be beneficial for healing and bone reparation after the surgical treatment of periapical lesions.


In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype.
To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A) of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.


An Autopsy Case of Injuries Caused by Automobile Dragging for a Distance of 3.4 km Without Thoracoabdominal Organ Injuries.
Dragging injuries caused by automobiles involved in an accident are occasionally reported; however, those without injury to the thoracoabdominal organs are rare. We present an autopsy case of a man in his 20s found dead on the road after being dragged by a passenger automobile for a distance of 3.4 km. The accident caused fatal dragging injuries but no thoracoabdominal injuries. The victim appeared to be drunk and was lying on the road in front of the parked automobile. Dragging injuries are a unique type of traffic accident that sometimes result from limited and poor visibility due to darkness, rain, or fog. In particular, lying on the road in a drunken state is a specific risk factor for dragging injuries. The dragging distance, road-surface properties, strength of pressure applied by the underbody of the automobile, and the victim's posture are considered to affect the distribution and degree of dragging injuries. Based on autopsy findings and eyewitness testimonies, we discuss the injury mechanism and attempt to reconstruct the accident.


Cloning of the debranching-enzyme gene from Thermoanaerobium brockii into Escherichia coli and Bacillus subtilis.
The gene for an enzyme with single or dual specificity on complex carbohydrates has been transferred from its native host (Thermoanaerobium brockii), a thermophilic anaerobe, into Escherichia coli and Bacillus subtilis. Most of the gene coding region is in a 2.2-kilobase PstI fragment that is common to the E. coli and B. subtilis chimeric vectors pCPC902 and pCPC903, respectively. Although the T. brockii debranching enzyme secreted from B. subtilis was unglycosylated and had less thermostability, more enzyme was secreted from B. subtilis (0.80 to 1.0 U/ml) than from T. brockii (0.23 U/ml). E. coli did not export any measurable enzyme. From the fermentation broth of B. subtilis containing pCPC903, three active species of the debranching enzyme were separated; two species are possibly protease digestion products of the larger protein (105,000 molecular weight). Whereas the enzyme can cleave all of the alpha-1----6 glucosidic linkages (and none of the alpha-1----4 bonds) in pullulan, it hydrolyzed mostly alpha-1----4 and very few of the alpha-1----6 linkages in starch. Upon hydrolysis of pullulan by the enzyme, only maltotriose was produced, while starch was digested to various-sized oligomers.


Sustained-release isradipine compared with spirapril in the treatment of elderly patients with isolated systolic hypertension.
The benefits of treating isolated systolic hypertension (ISH) have been established, but the most appropriate choice of drug is still uncertain. For this reason, a sustained-release formulation of isradipine was compared with spirapril in a double-blind randomized study in elderly Chinese patients with ISH. The dosage was titrated if necessary after 4 weeks of treatment. The reduction in systolic/diastolic blood pressure after 8 weeks was similar for both treatments--20/10 mm Hg with isradipine versus 24/6 mm Hg with spirapril--measured in the supine position. There were no orthostatic symptoms and both treatments were well tolerated.


Detection of antibodies of the IgM class in sera of patients recently infected with influenza viruses.
Sucrose density gradient ultracentrifugation can be used to detect specific 19S antibodies of the IgM class in the sera of patients recently infected with influenza A virus, provided steps are taken to remove non-specific inhibitors of haemagglutination. The usefulness of the procedure for the diagnosis of influenza requires further evaluation.


Performance indicators: healthcare professionals' views.
Purpose - The purpose of this paper is to capture factors behind professional views of indicator usefulness as a common structure for assessing healthcare performance and their important characteristics to design limited key performance indicators (PIs) for holistic hospital management. Design/methodology/approach - Two surveys were conducted using self-administered questionnaires, in which hospital manager/staff respondents were asked to rate the 52 PIs' usefulness. In total, 228 manager and 894 staff responses were collected. Findings - Eight factors were elicited from manager and staff responses as performance measures with 72 percent cumulative variance accounted for. Hospital managers and staff showed similar performance measure perceptions: high-utility acknowledgment on safety, operational efficiency and patient/employee satisfaction but relatively low-employee development concerns. Manager indicator usefulness perceptions were rather homogeneous and significantly higher than staff for almost all performance measures. Practical implications - Homogeneous manager views mean that a single key PI set for hospital management may be established regardless of hospital attributes. The following aspects may be measures that should be managed in a healthcare organization based on their key PIs: patient/employee safety, operational efficiency, financial effectiveness and patient/employee satisfaction. Originality/value - This is a pilot study on hospital management PIs in Japan. The eight-dimensional factor structure and findings about healthcare provider perceptions may be useful for healthcare management.


An evaluation of the CARL manikin for use in "patient-free" real ear measurement: consistency and comparison to normative data.
Simulation-based learning experiences provide low-risk opportunities for procedural training and practice in audiology. A series of real ear measurements (REM) were completed using Clinical Assistant for Research and Learning (CARL) manikins to determine expected responses and to compare to normative data. (1) Real-ear Unaided Response (REUR) curves were measured with one CARL and each of three ear styles. (2) Test/retest reliability was evaluated by repeating each REUR. (3) Real ear to coupler difference (RECD) values for foam-tip and custom earmolds were calculated. (4) The reliability across copies of the CARL heads was evaluated by comparing REUR measurement from one set of ears on 4 heads. Four adult CARL manikins and thirty ears (5 sets of large, small, and bent). Within each ear category, the average difference across frequencies from one ear to the next was less than 2.5 dB with no significant individual difference more than 5.8 dB. Test/retest reliability was excellent. Typical REUR and RECD curves were created for each ear style and compared to published data on human ears. REM using the adult CARL head are predictable and repeatable making this simulator a good tool for audiological training.


NFP: An R Package for Characterizing and Comparing of Annotated Biological Networks.
Large amounts of various biological networks exist for representing different types of interaction data, such as genetic, metabolic, gene regulatory, and protein-protein relationships. Recent approaches on biological network study are based on different mathematical concepts. It is necessary to construct a uniform framework to judge the functionality of biological networks. We recently introduced a knowledge-based computational framework that reliably characterized biological networks in system level. The method worked by making systematic comparisons to a set of well-studied "basic networks," measuring both the functional and topological similarities. A biological network could be characterized as a spectrum-like vector consisting of similarities to basic networks. Here, to facilitate the application, development, and adoption of this framework, we present an R package called NFP. This package extends our previous pipeline, offering a powerful set of functions for Network Fingerprint analysis. The software shows great potential in biological network study. The open source NFP R package is freely available under the GNU General Public License v2.0 at CRAN along with the vignette.


Universality of the DNA methylation codes in Eucaryotes.
Genetics and epigenetics are tightly linked heritable information classes. Question arises if epigenetics provides just a set of environment dependent instructions, or whether it is integral part of an inheritance system. We argued that in the latter case the epigenetic code should share the universality quality of the genetic code. We focused on DNA methylation. Since availability of DNA methylation data is biased towards model organisms we developed a method that uses kernel density estimations of CpG observed/expected ratios to infer DNA methylation types in any genome. We show here that our method allows for robust prediction of mosaic and full gene body methylation with a PPV of 1 and 0.87, respectively. We used this prediction to complement experimental data, and applied hierarchical clustering to identify methylation types in ~150 eucaryotic species covering different body plans, reproduction types and living conditions. Our analysis indicates that there are only four gene body methylation types. These types do not follow phylogeny (i.e. phylogenetically distant clades can have identical methylation types) but they are consistent within clades. We conclude that the gene body DNA methylation codes have universality similar to the universality of the genetic code and should consequently be considered as part of the inheritance system.


Changing the culture of care for dying patients.
A care setting's culture will affect the roles played by nurses and people who are dying. The theory of malignant social psychology developed in dementia care can provide insight into the treatment of dying people. A major cultural shift is required if the needs of dying people are to be met and the balance of power altered.


Characteristics of skeletal muscle ecto-ATPase in situ.
The properties of a cell surface nucleoside 5'-triphosphatase have been studied in small, intact, frog skeletal muscles, as a means of distinguishing the enzyme from other adenosine 5'-triphosphatases and of understanding its behaviour in the muscle membrane. The ectoenzyme in situ was shown to be a Ca2+- or Mg2+-activated ATPase liberating 7.5 +/- 0.4 (mean +/- SEM, n = 30) mumol of inorganic phosphate/g of muscle per 20 min, when the muscle was exposed to 2 mM ATP and 2 mM Ca2+ in Ringer's solution. The apparent Km for Mg2+ was 0.74 mM and for Ca2+ was 0.23 mM. A residual ATPase activity (20%) was found in the complete absence of divalent cations suggesting the existence of two ATPase types. A broad specificity toward nucleoside 5'-triphosphates was exhibited by the ecto-ATPase, but there was no nonspecific phosphatase activity. The enzyme was inhibited by La3+ and Cd2+, but was insensitive to ouabain, 2,4-dinitrophenol, oligomycin, and ruthenium red. Thus the ectoenzyme was not a Na+, K+-transport ATPase, was not an ATPase of mitochondrial origin, or a Ca2+-transport enzyme. Insulin had no effect. Inhibition by mersalyl, carbodiimide, and polar and cross-linking nonpolar nitrobenzene derivatives suggested that, for maximum activity, this membrane-bound enzyme required free sulfhydryl groups, certain free carboxyls, and an appreciable degree of hydrophobicity in its microenvironment.


A comparison of usability evaluation methods: heuristic evaluation versus end-user think-aloud protocol - an example from a web-based communication tool for nurse scheduling.
We evaluated a web-based communication tool for nurse scheduling using two common usability evaluation methods, heuristic evaluation and end-user think aloud protocol. We found that heuristic evaluation performed by human-computer interaction (HCI) experts revealed more general interface design problems, while end-users' think-aloud protocols identified more obstacles to task performance. To provide the most effective and thorough evaluation results, a combination of heuristic evaluation and end-user think-aloud protocol is recommended.


Ammonia-oxidizing bacteria and archaea in sediments of the Gulf of Mexico.
The diversity (richness and community composition) of ammonia-oxidizing archaea (AOA) and bacteria (AOB) within sediments of the Gulf of Mexico was examined. Using polymerase chain reaction primers designed to specifically target the archaeal ammonia monooxygenase-subunit (amoA) gene and bacterial amoA gene, we found AOA and AOB to be present in all three sampling sites. Archaeal amoA libraries were dominated by a few widely distributed Nitrosopumilus-like sequence types, whereas AOB diversity showed significant variation in both richness and community composition. Majority of the bacterial amoA sequences recovered belong to Betaproteobacteria and very few belong to Gammaproteobacteria. Results suggest that water depth and nutrient availability were identified as potential drivers that affected the selection of the AOA and AOB communities. Besides influencing the abundance of individual taxa, these environmental factors also had an impact on the overall richness of the overall AOA and AOB communities. The richness and diversity of AOA and AOB genes were higher at the shallowest sediments (100 m depth) and the deepest sediments (1300 m depth). The reduced diversity in the deepest sediments could be explained by much lower nutrient availability.


NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1.
The molecular basis underlying glioblastoma (GBM) heterogeneity and plasticity is not fully understood. Using transcriptomic data of human patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factor FOSL1 as a key regulator of the mesenchymal (MES) subtype. We provide a mechanistic basis to the role of the neurofibromatosis type 1 gene (NF1), a negative regulator of the RAS/MAPK pathway, in GBM mesenchymal transformation through the modulation of FOSL1 expression. Depletion of FOSL1 in NF1-mutant human BTSCs and Kras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature and reduction in stem cell properties and in vivo tumorigenic potential. Our data demonstrate that FOSL1 controls GBM plasticity and aggressiveness in response to NF1 alterations.


Activity of drug combinations against dormant Mycobacterium tuberculosis.
Aerobic (5-day-old cultures) and nonreplicating (dormant) Mycobacterium tuberculosis (5-, 12-, and 19-day-old cultures) bacteria were treated with rifampin (R), moxifloxacin (MX), metronidazole (MZ), amikacin (AK), or capreomycin (CP) for 7, 14, and 21 days. R-MX-MZ-AK and R-MX-MZ-CP killed both aerobic and dormant bacilli in 21 days, as shown by lack of regrowth in solid and liquid media. R-MX-MZ-AK and R-MX-MZ-CP also caused a strong decrease of nonreplicating bacilli in 7 days in a cell-based dormancy model.


Differentiation in medulloblastomas and other primitive neuroectodermal tumours.
Fifty-four cases of primitive neuroectodermal tumour (PNET) including 47 medulloblastomas, were examined for evidence of neuronal and glial differentiation, using antibodies to neuron-specific enolase (NSE), neurofilament protein (NF), and glial fibrillary acidic protein (GFAP). In 30 of the cases, antibodies to vimentin, alphafetoprotein, cytokeratin, epithelial membrane antigen and lymphoid markers were also used. Most of the 47 medulloblastomas in the group were NSE positive but NF negative; about half were GFAP positive and three of them were positive for both neuronal markers and for GFAP. Vimentin was demonstrated in four cases and was not always co-expressed with GFAP. Medulloblastomas were negative for all the other markers. Supratentorial PNETs were sometimes positive with neuronal markers but were GFAP negative. The cell specificity of these markers and the interpretation of immunocytochemical findings are discussed in relation to differentiation potential in primitive neuroectodermal tumours.


Development of image analysis techniques as a tool to detect and quantify morphological changes in anaerobic sludge: II. Application to a granule deterioration process triggered by contact with oleic acid.
Image analysis techniques are applied to monitor the morphological changes in granular sludge present in an expanded granular sludge blanket (EGSB) reactor fed with oleic acid. Deterioration of granular sludge was monitored along the trial period by measuring the percentage of aggregates smaller than 1 mm (in terms of Feret diameter) either in terms of projected area or in terms of number of aggregates. A good correlation was obtained between these values and the percentage of aggregates smaller than 1 mm were physically sorted and quantified by the volatile suspended solid content. The ratio of total filaments length to cross-sectional area of aggregates defined as LfA, was applied to quantify the dispersion level of the granular sludge, which increased until day 141 and remained almost invariant afterwards. LfA was sensitive to the sludge deterioration process and was able to indicate, with the anticipation of about 1 month, the most significant biomass washout episode that occurred in the trial period. A mechanism of filaments' release, detachment and selective washout was proposed to explain the action of LfA from this viewpoint. The equivalent diameter of the bottom aggregates larger than 1 mm increased with the increase on the amount of long chain fatty acids associated with the biomass by mechanisms of adsorption, precipitation, or entrapment. After a threshold value of about 200 mg COD-LCFA gVSS (COD = chemical oxygen demand; LCFA = long chain fatty acids; VSS = volatile suspended solids), a migration of granular sludge from the bottom to a top-floating layer was evident.


The role of neurotensin as a novel biomarker in the endoscopic screening of high-risk population for developing colorectal neoplasia.
Colorectal cancer screening programs aim at early detection of cancer to reduce incidence rates and mortality. The objective of this study is to identify the role of neurotensin in the endoscopic screening of high-risk population for developing colorectal neoplasia. Blood samples from patients referred for urgent colonoscopy to investigate symptoms suspicious of colorectal cancer were collected. Blood neurotensin levels were measured using enzyme-linked immunosorbent assay. Colonoscopy findings were used as reference for determining the diagnostic accuracy of blood neurotensin. The study comprised 26 patients in total: 12 healthy and 14 with colon pathology (13 high-grade dysplasia adenomatous polyps, 1 adenocarcinoma). There were no statistically significant differences in the clinical and biochemical parameters between colon pathology and healthy group except neurotensin levels. Pathology in colon was associated with 3.7-fold increase in NT levels. In multivariate analysis, patients with pathology in colon have increased serum neurotensin levels compared to controls adjusted for age, gender, BMI and co-morbidities. The value of 12.93 pg/ml is associated with 87.5% sensitivity and 91.7% specificity for discriminating the colon pathology from normal colonic epithelium (p = 0.001). Neurotensin plasma values differentiate healthy people from patients suffering from colonic pathologies such as adenomatous polyps and cancer. The use of neurotensin as a potential endoscopic screening tool for identifying high-risk population for developing colorectal cancer is promising, but much has to be done before it is validated in larger scale prospective studies.


[The subjects of the controversy of energy theory and the concept of "labor intensity" in labor physiology from the 1930's to 1950's in Japan. (1) Energy theory and methodology].
An analysis of the subjects of the controversy of energy theory, which was discussed over the various fields of labor science at 1930s-50s in Japan is as follows: (1) This theory was to re-arrange rationally, work in order to reduce the consumption of energy in human actions. It, moreover, was considered to be the standard of the wage adjustment. (2) It became popular since the working powers were terribly wasted by the industrial mobilization during WWII, and when the starvation wages spread throughout the country after the defeat. (3) This theory played an important role to synthesize the academic achievements of various fields such as labor economic, labor physiology, labor psychology and others.


Type of retirement as a determinant of pre- and post-retirement hospital in-patient care use: a prospective study.
We examined prospectively the use of all-cause hospital in-patient care among public sector employees by using a 3-year pre- and post-retirement study window. A total of 5269 participants of the Finnish Longitudinal Study of Municipal Employees had retired during January 1984 and July 2000. They had register-based data on retirement (non-disability retirement n = 3411, men 40%, and diagnose-specific disability retirement n = 1858, men 50%) and all-cause hospital in-patient admissions and discharges. Analyses were conducted using Generalized Estimating Equation model. The prevalence of hospital care use for non-disability retirees remained stable during the 6-year study window. The rate ratio (RR) for hospital care use increased in the year prior to retirement for men and women who transitioned into disability retirement due to cardiovascular disease and for women with disability due to mental disease. The RRs for hospital care use in the post-retirement year decreased for men who retired due to cardiovascular disease or mental disorders and for women who retired due to cardiovascular or musculoskeletal diseases. An increase in hospital care preceding retirement in major diagnosis-specific disability retirement groups was followed by various patterns of decrease in the need of care indicated a beneficial health effect of retirement.


Serum Periostin Is Negatively Correlated With Exposure to Formaldehyde and Volatile Organic Compounds in Children.
Epidemiological studies have shown that exposure to tobacco smoke causing irritation and inflammation in the airways tends to reduce serum periostin concentrations in adults. We now investigate prospective cross-sectional study on 135 Korean students aged 7 years in the first grade who were participating in the Seongnam Atopy Project for Children's Happiness 2016 (SAP₂₀₁₆) cohort. To the best of our knowledge, this is the first study to show significant inverse correlations between serum periostin concentration and exposure to xylene and formaldehyde in children. Our findings suggested the need for caution in using the serum periostin level as a marker for allergic diseases, since exposure to volatile organic compounds and formaldehyde may confound the interpretation of these results.


Variation in faecal digestibility values related to feed efficiency traits of grower-finisher pigs.
Providing pigs a diet that matches their nutrient requirements involves optimizing the diet based on the nutrient digestibility values of the considered feed ingredients. Feeding the same quantity of a diet to pigs with similar BW but with different requirements, however, can result in a different average daily gain (ADG) and backfat thickness (BF) between pigs. Digestibility may contribute to this variation in efficiency. We investigated variation in feed efficiency traits in grower-finisher pigs associated with variation in faecal digestibility values, independent of feed intake at the time of measuring faecal digestibility. Considered traits were ADG, average daily feed intake (ADFI), feed conversion ratio (FCR), BF and residual feed intake (RFI). Feed intake, BW, and BF data of one hundred and sixty three-way crossbreed grower-finisher pigs (eighty female and eighty male) were collected during two phases, from day 0 of the experiment (mean BW 23 kg) till day 56 (mean BW 70 kg) and from day 56 to slaughter (mean BW 121 kg). Pigs were either fed a diet based on corn/soybean meal or a more fibrous diet based on wheat/barley/by-products, with titanium dioxide as indigestible marker. Faecal samples of one hundred and five pigs were collected on the day before slaughter and used to determine apparent faecal digestibility of DM, ash, organic matter (OM), CP, crude fat (CFat), crude fibre (CF), and to calculate the digestibility of nonstarch polysaccharides (NSPs) and energy (E). The effects of diet, sex and covariate feed intake at sampling (FIs) on faecal digestibility values were estimated and were significant for all except for CFat. Faecal digestibility values of each individual pig determined at the day before slaughter, corrected for diet, sex and FIs, were used to estimate their association with ADG, ADFI, FCR, BF, and RFI. In the first phase, a one percent unit increase in faecal digestibility of DM, ash, OM, E, CP, CFat, CF, NSP, and Ash individually was related to 0.01-0.03 unit reduction in FCR and 6-23 g/day reduction in RFI. A unit increase in CP digestibility was related to 0.1 mm increase in BF and 10 g/day increase in ADG. In the second phase, a one percent unit increase in faecal digestibility of DM, CP and Ash was related to a decrease of 16-20 g/day in RFI. In conclusion, the relationship between variation in feed efficiency traits and faecal digestibility values is different across the developmental stages of a pig.


Hybrid optical materials of plasmon-coupled CdSe/ZnS coreshells for photonic applications.
A hybrid optical nanostructure of plasmon-coupled SQDs was developed for photonic applications. The coupling distances between the mono-layers of Au nanoparticles with a surface concentration of ~9.18 × 10-4 nm-2 and CdSe/ZnS SQDs with that of ~3.7 × 10-3 nm-2 were controlled by PMMA plasma etching. Time-resolved spectroscopy of plasmon-coupled SQDs revealed a strong shortening of the longest lifetime and ~9-fold PL enhancement. Polarization-resolved PL spectroscopy displayed linear polarization and depolarization at near- and far-field plasmon-coupling, respectively. The physical origin of PL enhancement could be attributable to both the large local field enhancement and the fast resonant energy transfer.


Subject-specific computational simulation of left ventricular flow based on magnetic resonance imaging.
A detailed investigation of left ventricle (LV) flow patterns could improve our understanding of the function of the heart and provide further insight into the mechanisms of heart failure. This study presents patient-specific modelling with magnetic resonance imaging (MRI) to investigate LV blood flow patterns in normal subjects. In the study, the prescribed LV wall movements based on the MRI measurements drove the blood flow in and out of the LV in computational fluid dynamics simulation. For the six subjects studied, the simulated LV flow swirls towards the aortic valve and is ejected into the ascending aorta with a vertical flow pattern that follows the left-hand rule. In diastole, the inflow adopts a reasonably straight route (with no significant secondary flow) towards the apex in the rapid filling phase with slight variations in the jet direction between different cases. When the jet reaches about two thirds of the distance from the inflow plane to the apex, the blood flow starts to change direction and swirls towards the apex. In the more slowly filling phase, a centrally located jet is evident with vortices located on both sides of the jet on an anterior-posterior plane that passes through the mitral and aortic valves. In the inferior-superior plane, a main vortex appears for most of the cases in which an anticlockwise vortex appears for three cases and a clockwise vortex occurs for one case. The simulated flow patterns agree well qualitatively with MRI-measured flow fields.


Fluidic dielectrophoresis: The polarization and displacement of electrical liquid interfaces.
Traditional particle-based dielectrophoresis has been exploited to manipulate bubbles, particles, biomolecules, and cells. In this work, we investigate analytically and experimentally how to utilize Maxwell-Wagner polarization to initiate fluidic dielectrophoresis (fDEP) at electrically polarizable aqueous liquid-liquid interfaces. In fDEP, an AC electric field is applied across a liquid electrical interface created between two coflowing fluid streams with different electrical properties. When potentials as low as 2 volts are applied, we observe a frequency-dependent interfacial displacement that is dependent on the relative differences in the electrical conductivity (Δσ) and dielectric constant (Δɛ) between the two liquids. At low frequency this deflection is independent of dielectric constant, while at high frequency it is independent of electrical conductivity. At intermediate frequencies, we observe an fDEP cross-over frequency that is independent of applied voltage, sensitive to both fluid electrical properties, and where no displacement is observed. An analytical fDEP polarization model is presented that accurately predicts the liquid interfacial cross-over frequency, the dependence of interfacial displacement on liquid electrical conductivity and dielectric constant, and accurately scales the measured fDEP displacement data. The results show that miscible aqueous liquid interfaces are capable of polarizing under AC electric fields, and being precisely deflected in a direction and magnitude that is dependent on the applied electric field frequency.


Concussion sideline management intervention for rugby union leads to reduced concussion claims.
The effectiveness of a concussion management education programme (CMEP) in rugby in reducing the number and cost of concussion/brain injury (CBI) moderate to serious claims (MSC) was assessed. A RugbySmart educational video and a sideline concussion check (SCC) tool comprised the CMEP. Over 30,000 SCC, providing information on management of suspected concussion among community level rugby players prior to seeking medical treatment, were distributed from July 2003 to June 2005. Each year approximately 10,000 coaches and 2,000 referees participated in RugbySmart. From 2003 to 2005 new rugby CBI MSC reduced by 10.7% (actual) and 58.2% (forecast). Rugby player numbers, new non-sport CBI MSC and new sport MSC all increased by 13.6%, 16.9% and 24.6% respectively in the same period. The median number of days between CBI injury and the player seeking medical treatment decreased from six days to four days. Cost savings after CMEP were 690 USD dollars, 690 (actual) to 3,354,780 USD dollars (forecast). The two-year cost of CMEP was 54,810 USD dollars returning 12.60 USD dollars (actual) and 61.21 USD dollars (forecast) for every 1 USD dollar invested (ROI). CMEP provided community coaches and managers with education on minimum best practice for managing suspected concussion, contributed towards ROI and savings for CBI MSC in rugby.