Effectiveness and cost-effectiveness of a minimal psychological intervention to reduce non-severe depression in chronically ill elderly patients: the design of a randomised controlled trial [ISRCTN92331982].
Depression is a prevalent disorder in chronically ill elderly persons. It may decrease quality of life, and increase functional disability, medical costs, and healthcare utilisation. Because patients may slip into a downward spiral, early recognition and treatment of depression is important. Depression can be treated with antidepressants or psychological interventions; the latter can also be applied by trained paraprofessionals. In this paper, we describe the design of the DELTA study (Depression in Elderly with Long-Term Afflictions). The first objective of the DELTA study is to evaluate the effectiveness and cost-effectiveness of a minimal psychological intervention (MPI) to reduce depression in chronically ill elderly patients. The second objective is to evaluate whether a potential effect of the MPI may differ between types of chronic illnesses. The tailor-made intervention is administered by nurses, who are trained in the principles of cognitive behavioural therapy and self-management. DELTA is a two-armed randomised controlled trial, comparing MPI to usual care. A total number of 180 patients with diabetes mellitus type II (DM) and 180 patients with chronic obstructive pulmonary disease (COPD), who in addition suffer from non-severe depression, will be included in the study. In our study, non-severe depression is defined as having minor depression, mild major depression or moderate major depression. The primary outcome measure is depression using the Beck Depression Inventory. Secondary outcome measures include quality of life, daily functioning, self-efficacy, autonomy, and participation. In the economic evaluation, cost-effectiveness and cost-utility ratios will be calculated. Furthermore, a process evaluation will be carried out. Analyses will include both univariate and multivariate techniques and according to the intention to treat principle. The economic evaluation will be done from a societal perspective and data of the process evaluation will be analysed using descriptive techniques. A total number of 361 patients has been included in the study. All interventions have been administered and follow-up data will be complete in September 2006. Preliminary results from the process evaluation indicate that patients' satisfaction with the intervention is high. If this intervention proves to be effective, implementation of the DELTA intervention is considered and anticipated.


AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival.
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy associated with Notch pathway mutations. While both normal activated and leukemic T cells can utilize aerobic glycolysis to support proliferation, it is unclear to what extent these cell populations are metabolically similar and if differences reveal T-ALL vulnerabilities. Here we show that aerobic glycolysis is surprisingly less active in T-ALL cells than proliferating normal T cells and that T-ALL cells are metabolically distinct. Oncogenic Notch promoted glycolysis but also induced metabolic stress that activated 5' AMP-activated kinase (AMPK). Unlike stimulated T cells, AMPK actively restrained aerobic glycolysis in T-ALL cells through inhibition of mTORC1 while promoting oxidative metabolism and mitochondrial Complex I activity. Importantly, AMPK deficiency or inhibition of Complex I led to T-ALL cell death and reduced disease burden. Thus, AMPK simultaneously inhibits anabolic growth signaling and is essential to promote mitochondrial pathways that mitigate metabolic stress and apoptosis in T-ALL.


The potential of amoeba-based processes for natural product syntheses.
The identification of novel platform organisms for the production and discovery of small molecules is of high interest for the pharmaceutical industry. In particular, the structural complexity of most natural products with therapeutic potential restricts an industrial production since chemical syntheses often require complex multistep routes. The amoeba Dictyostelium discoideum can be easily cultivated in bioreactors due to its planktonic growth behavior and contains numerous polyketide and terpene synthase genes with only a few compounds being already elucidated. Hence, the amoeba both bears a wealth of hidden natural products and allows for the development of new bioprocesses for existing pharmaceuticals. In this mini review, we present D. discoideum as a novel platform for the production of complex secondary metabolites and discuss its suitability for industrial processes. We also provide initial insights into future bioprocesses, both involving bacterial coculture setups and for the production of plant-based pharmaceuticals.


A Tcf4-positive mesodermal population provides a prepattern for vertebrate limb muscle patterning.
Nai;ve myogenic cells migrate from the somites into the developing vertebrate limb, where they simultaneously differentiate into myotubes and form distinct anatomical muscles. Limb signals have been hypothesized to direct the pattern of muscles formed, but the molecular nature of these signals and the identity of the cells that produce them have remained unclear. We have identified a population of lateral plate-derived limb mesodermal cells in both chick and mouse that expresses the transcription factor Tcf4 in a muscle-specific pattern independently of the muscle cells themselves. Functional experiments in the chick demonstrate that TCF4 and the Wnt-beta-catenin pathway in these limb mesodermal cells are critical for muscle patterning. We propose that Tcf4-expressing cells establish a prepattern in the limb mesoderm that determines the sites of myogenic differentiation and thus establishes the basic pattern of limb muscles.


Evaluation of kidney function throughout the heart failure trajectory - a position statement from the Heart Failure Association of the European Society of Cardiology.
Appropriate interpretation of changes in markers of kidney function is essential during the treatment of acute and chronic heart failure. Historically, kidney function was primarily assessed by serum creatinine and the calculation of estimated glomerular filtration rate. An increase in serum creatinine, also termed worsening renal function, commonly occurs in patients with heart failure, especially during acute heart failure episodes. Even though worsening renal function is associated with worse outcome on a population level, the interpretation of such changes within the appropriate clinical context helps to correctly assess risk and determine further treatment strategies. Additionally, it is becoming increasingly recognized that assessment of kidney function is more than just glomerular filtration rate alone. As such, a better evaluation of sodium and water handling by the renal tubules allows to determine the efficiency of loop diuretics (loop diuretic response and efficiency). Also, though neurohumoral blockers may induce modest deteriorations in glomerular filtration rate, their use is associated with improved long-term outcome. Therefore, a better understanding of the role of cardio-renal interactions in heart failure in symptom development, disease progression and prognosis is essential. Indeed, perhaps even misinterpretation of kidney function is a leading cause of not attaining decongestion in acute heart failure and insufficient dosing of guideline-directed medical therapy in general. This position paper of the Heart Failure Association Working Group on Cardio-Renal Dysfunction aims at improving insights into the interpretation of renal function assessment in the different heart failure states, with the goal of improving heart failure care.


Metallic zinc- assisted synthesis of Ti3+ self-doped TiO2 with tunable phase composition and visible-light photocatalytic activity.
Stable Ti(3+) self-doped TiO(2) with tunable phase composition and highly efficient visible-light photoactivity (ca. 32.7 times stronger than an undoped sample for ˙OH formation) was synthesized via a facile metallic zinc-assisted method. The surface Ti(3+) species can be stabilized by Zn doping, and the photocatalytic selectivity can be regulated by the phase composition.


Resveratrol Inhibits ROS-Promoted Activation and Glycolysis of Pancreatic Stellate Cells via Suppression of miR-21.
Activation of pancreatic stellate cells (PSCs) initiates pancreatic fibrosis in chronic pancreatitis and furnishes a niche that enhances the malignancy of pancreatic cancer cells (PCCs) in pancreatic ductal adenocarcinoma (PDAC). Resveratrol (RSV), a natural polyphenol, exhibits potent antioxidant and anticancer effects. However, whether and how RSV influences the biological properties of activated PSCs and the effects of these changes on tumor remain unknown. In the present study, we found that RSV impeded hydrogen peroxide-driven reactive oxygen species- (ROS-) induced activation, invasion, migration, and glycolysis of PSCs. In addition, miR-21 expression in activated PSCs was downregulated after RSV treatment, whereas the PTEN protein level increased. miR-21 silencing attenuated ROS-induced activation, invasion, migration, and glycolysis of PSCs, whereas the overexpression of miR-21 rescued the responses of PSCs treated with RSV. Moreover, RSV or N-acetyl-L-cysteine (NAC) administration or miR-21 knockdown in PSCs reduced the invasion and migration of PCCs in coculture, and the effects of RSV were partly reversed by miR-21 upregulation. Collectively, RSV inhibits PCC invasion and migration through suppression of ROS/miR-21-mediated activation and glycolysis in PSCs. Therefore, targeting miR-21-mediated glycolysis by RSV in tumor stroma may serve as a new strategy for clinical PDAC prevention or treatment.


Does competition drive character differences between species on a macroevolutionary scale?
Sympatric sister species generally have a degree of phenotypic differentiation that allows them to coexist. It has been well documented that phenotypic similarity results, through resource competition, in one of two major outcomes: local extinction of either competitor or character displacement. Limiting similarity suggests that there is a maximum degree of phenotypic niche overlap with which similar species may coexist. Breaching that maximum would result in exclusion. Character displacement, on the other hand, implies that the species differentiate phenotypically so that resource competition is reduced to the point where coexistence is possible. While it has been suggested that these theories have the potential to accelerate (character displacement) or limit phenotypic evolution (competitive exclusion) on microevolutionary time scales, their effects on macroevolution remain under-studied. If competition accelerates evolution on a macroevolutionary scale, one would expect that phenotypic diversity increases as novel species 'push aside' existing species. On the other hand, one might also expect that phenotypic evolution comes to a halt as novel species are trapped in the (ever decreasing) phenotypic space not yet occupied by existing species, except at the extremes of the phenotypic spectrum. Studying the current geographical ranges of more than 3000 extant species representing 29 mammalian families and their respective body masses, I found little evidence of competition accelerating body size differentiation between species.


Comparison of the light-harvesting networks of plant and cyanobacterial photosystem I.
With the availability of structural models for photosystem I (PSI) in cyanobacteria and plants it is possible to compare the excitation transfer networks in this ubiquitous photosystem from two domains of life separated by over one billion years of divergent evolution, thus providing an insight into the physical constraints that shape the networks' evolution. Structure-based modeling methods are used to examine the excitation transfer kinetics of the plant PSI-LHCI supercomplex. For this purpose an effective Hamiltonian is constructed that combines an existing cyanobacterial model for structurally conserved chlorophylls with spectral information for chlorophylls in the Lhca subunits. The plant PSI excitation migration network thus characterized is compared to its cyanobacterial counterpart investigated earlier. In agreement with observations, an average excitation transfer lifetime of approximately 49 ps is computed for the plant PSI-LHCI supercomplex with a corresponding quantum yield of 95%. The sensitivity of the results to chlorophyll site energy assignments is discussed. Lhca subunits are efficiently coupled to the PSI core via gap chlorophylls. In contrast to the chlorophylls in the vicinity of the reaction center, previously shown to optimize the quantum yield of the excitation transfer process, the orientational ordering of peripheral chlorophylls does not show such optimality. The finding suggests that after close packing of chlorophylls was achieved, constraints other than efficiency of the overall excitation transfer process precluded further evolution of pigment ordering.


Whole-genome de novo sequencing, combined with RNA-Seq analysis, reveals unique genome and physiological features of the amylolytic yeast Saccharomycopsis fibuligera and its interspecies hybrid.
Genomic studies on fungal species with hydrolytic activity have gained increased attention due to their great biotechnological potential for biomass-based biofuel production. The amylolytic yeast Saccharomycopsis fibuligera has served as a good source of enzymes and genes involved in saccharification. Despite its long history of use in food fermentation and bioethanol production, very little is known about the basic physiology and genomic features of S. fibuligera. We performed whole-genome (WG) de novo sequencing and complete assembly of S. fibuligera KJJ81 and KPH12, two isolates from wheat-based Nuruk in Korea. Intriguingly, the KJJ81 genome (~38 Mb) was revealed as a hybrid between the KPH12 genome (~18 Mb) and another unidentified genome sharing 88.1% nucleotide identity with the KPH12 genome. The seven chromosome pairs of KJJ81 subgenomes exhibit highly conserved synteny, indicating a very recent hybridization event. The phylogeny inferred from WG comparisons showed an early divergence of S. fibuligera before the separation of the CTG and Saccharomycetaceae clades in the subphylum Saccharomycotina. Reconstructed carbon and sulfur metabolic pathways, coupled with RNA-Seq analysis, suggested a marginal Crabtree effect under high glucose and activation of sulfur metabolism toward methionine biosynthesis under sulfur limitation in this yeast. Notably, the lack of sulfate assimilation genes in the S. fibuligera genome reflects a unique phenotype for Saccharomycopsis clades as natural sulfur auxotrophs. Extended gene families, including novel genes involved in saccharification and proteolysis, were identified. Moreover, comparative genome analysis of S. fibuligera ATCC 36309, an isolate from chalky rye bread in Germany, revealed that an interchromosomal translocation occurred in the KPH12 genome before the generation of the KJJ81 hybrid genome. The completely sequenced S. fibuligera genome with high-quality annotation and RNA-Seq analysis establishes an important foundation for functional inference of S. fibuligera in the degradation of fermentation mash. The gene inventory facilitates the discovery of new genes applicable to the production of novel valuable enzymes and chemicals. Moreover, as the first gapless genome assembly in the genus Saccharomycopsis including members with desirable traits for bioconversion, the unique genomic features of S. fibuligera and its hybrid will provide in-depth insights into fungal genome dynamics as evolutionary adaptation.


Dramatic increase of nitrite levels in hearts of anoxia-exposed crucian carp supporting a role in cardioprotection.
Nitrite (NO(2)(-)) functions as an important nitric oxide (NO) donor under hypoxic conditions. Both nitrite and NO have been found to protect the mammalian heart and other tissues against ischemia (anoxia)-reoxygenation injury by interacting with mitochondrial electron transport complexes and limiting the generation of reactive oxygen species upon reoxygenation. The crucian carp naturally survives extended periods without oxygen in an active state, which has made it a model for studying how evolution has solved the problems of anoxic survival. We investigated the role of nitrite and NO in the anoxia tolerance of this fish by measuring NO metabolites in normoxic, anoxic, and reoxygenated crucian carp. We also cloned and sequenced crucian carp NO synthase variants and quantified their mRNA levels in several tissues in normoxia and anoxia. Despite falling levels of blood plasma nitrite, the crucian carp showed massive increases in nitrite, S-nitrosothiols (SNO), and iron-nitrosyl (FeNO) compounds in anoxic heart tissue. NO(2)(-) levels were maintained in anoxic brain, liver, and gill tissues, whereas SNO and FeNO increased in a tissue-specific manner. Reoxygenation reestablished normoxic values. We conclude that NO(2)(-) is shifted into the tissues where it acts as NO donor during anoxia, inducing cytoprotection under anoxia/reoxygenation. This can be especially important in the crucian carp heart, which maintains output in anoxia. NO(2)(-) is currently tested as a therapeutic drug against reperfusion damage of ischemic hearts, and the present study provides evolutionary precedent for such an approach.


Standardized measurement of sensorimotor recovery in stroke trials: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable.
Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.


Optimizing first-line treatment options for patients with advanced NSCLC.
The median survival time for advanced non-small cell lung cancer (NSCLC) remains poor, despite years of research into new chemotherapy combinations. Platinum-based chemotherapy has long been the standard of care for the initial treatment of advanced NSCLC. While no one particular platinum-based chemotherapy regimen is definitely superior to the others (as demonstrated in the Eastern Cooperative Oncology Group's E1594 trial), three randomized phase III trials (the Southwest Oncology Group 9509, Italian Lung Cancer Project, and TAX326 trials) have recently demonstrated that taxane-platinum doublets are better tolerated than a combination of vinorelbine and cisplatin (VC). Moreover, a combination of docetaxel and cisplatin produced superior survival and quality of life than VC in the TAX326 study. Nonplatinum combinations, such as a taxane-gemcitabine doublet, appear promising and better tolerated than their platinum-based comparators in other studies. Efforts to evaluate chemotherapy specifically in elderly patients and in those with poor performance status (PS) have increased. Single-agent chemotherapy has been safely administered to these populations, but platinum-based doublet therapy may also be feasible in both elderly patients and patients with PS scores of 2. The addition of the monoclonal antibody against vascular endothelial growth factor, bevacizumab, to standard chemotherapy for patients with non-squamous cell advanced NSCLC significantly extended median survival in the E4599 randomized trial. Each incremental advance demonstrates that progress can be made in first-line treatment of advanced NSCLC.


Evidence on vulnerability and susceptibility to health risks associated with short-term exposure to particulate matter: a systematic review and meta-analysis.
Although there is strong evidence that short-term exposure to particulate matter is associated with health risks, less is known about whether some subpopulations face higher risks. We identified 108 papers published after 1995 and summarized the scientific evidence regarding effect modification of associations between short-term exposure to particulate matter and the risk of death or hospitalization. We performed a meta-analysis of estimated mortality associations by age and sex. We found strong, consistent evidence that the elderly experience higher risk of particular matter--associated hospitalization and death, weak evidence that women have higher risks of hospitalization and death, and suggestive evidence that those with lower education, income, or employment status have higher risk of death. Meta-analysis showed a statistically higher risk of death of 0.64% (95% confidence interval (CI): 0.50, 0.78) for older populations compared with 0.34% (95% CI: 0.25, 0.42) for younger populations per 10 μg/m3 increase of particulate matter with aerodynamic diameter ≤10 μm. Women had a slightly higher risk of death of 0.55% (95% CI: 0.41, 0.70) compared with 0.50% (95% CI: 0.34, 0.54) for men, but these 2 risks were not statistically different. Our synthesis on modifiers for risks associated with particulate matter can aid the design of air quality policies and suggest directions for future research. Studies of biological mechanisms could be informed by evidence of differential risks by population, such as by sex and preexisting conditions.


Semi-quantitative immunohistochemical detection of 5-hydroxymethyl-cytosine reveals conservation of its tissue distribution between amphibians and mammals.
5-Hydroxymethyl-cytosine (5-hmC) is a form of modified cytosine, which has recently attracted a considerable attention due to its potential role in transcriptional regulation. According to several reports 5-hydroxymethyl-cytosine distribution is tissue-specific in mammals. Thus, 5-hmC is enriched in embryonic cell populations and in adult neuronal tissue. Here, we describe a novel method of semi-quantitative immunohistochemical detection of 5-hmC and utilize it to assess the levels of this modification in amphibian tissues. We show that, similar to mammalian embryos, 5-hmC is enriched in axolotl tadpoles compared with adult tissues. Our data demonstrate that 5-hmC distribution is tissue-specific in amphibians, and that strong 5-hmC enrichment in neuronal cells is conserved between amphibians and mammals. In addition, we identify 5-hmC-enriched cell populations that are distributed in amphibian skin and connective tissue in a mosaic manner. Our results illustrate that immunochemistry can be successfully used not only for spatial identification of cells enriched with 5-hmC, but also for the semi-quantitative assessment of the levels of this epigenetic modification in single cells of different tissues.


Structural basis of lipid biosynthesis regulation in Gram-positive bacteria.
Malonyl-CoA is an essential intermediate in fatty acid synthesis in all living cells. Here we demonstrate a new role for this molecule as a global regulator of lipid homeostasis in Gram-positive bacteria. Using in vitro transcription and binding studies, we demonstrate that malonyl-CoA is a direct and specific inducer of Bacillus subtilis FapR, a conserved transcriptional repressor that regulates the expression of several genes involved in bacterial fatty acid and phospholipid synthesis. The crystal structure of the effector-binding domain of FapR reveals a homodimeric protein with a thioesterase-like 'hot-dog' fold. Binding of malonyl-CoA promotes a disorder-to-order transition, which transforms an open ligand-binding groove into a long tunnel occupied by the effector molecule in the complex. This ligand-induced modification propagates to the helix-turn-helix motifs, impairing their productive association for DNA binding. Structure-based mutations that disrupt the FapR-malonyl-CoA interaction prevent DNA-binding regulation and result in a lethal phenotype in B. subtilis, suggesting this homeostatic signaling pathway as a promising target for novel chemotherapeutic agents against Gram-positive pathogens.


Plasma Neurofilament Light Chain Levels Are Elevated in Children and Young Adults With Wolfram Syndrome.
Wolfram syndrome is a rare disease caused by pathogenic variants in the WFS1 gene with progressive neurodegeneration. As an easily accessible biomarker of progression of neurodegeneration has not yet been found, accurate tracking of the neurodegenerative process over time requires assessment by costly and time-consuming clinical measures and brain magnetic resonance imaging (MRI). A blood-based measure of neurodegeneration, neurofilament light chain (NfL), is relatively inexpensive and can be repeatedly measured at remote sites, standardized, and measured in individuals with MRI contraindications. To determine whether NfL levels may be of use in disease monitoring and reflect disease activity in Wolfram syndrome, plasma NfL levels were compared between children and young adults with Wolfram syndrome (n = 38) and controls composed of their siblings and parents (n = 35) and related to clinical severity and selected brain region volumes within the Wolfram group. NfL levels were higher in the Wolfram group [median (interquartile range) NfL = 11.3 (7.8-13.9) pg/mL] relative to controls [5.6 (4.5-7.4) pg/mL]. Within the Wolfram group, higher NfL levels related to worse visual acuity, color vision and smell identification, smaller brainstem and thalamic volumes, and faster annual rate of decrease in thalamic volume over time. Our findings suggest that plasma NfL levels can be a powerful tool to non-invasively assess underlying neurodegenerative processes in children, adolescents and young adults with Wolfram syndrome.


Comparison of Hemodynamic Performance and Clinical Results with EVAHEART Versus HeartMate II.
This study aimed to compare the hemodynamic performance and clinical results of the EVAHEART and HeartMate II left ventricular assist devices (LVADs). From 2007 to 2016, fourteen patients received EVAHEART and 28 received HeartMate II at our center. Early survival, driveline infection, and neurologic events were evaluated. Hemodynamic performance was evaluated with transthoracic echocardiography and right heart catheterization. Mean follow-up was 35.5 ± 14.8 months for EVAHEART and 29.8 ± 6.5 months for HeartMate II. Survival rates were comparable between the two groups. After 24 months, freedom from driveline infection was 28% with EVAHEART, and 85% with HeartMate II; freedom from neurologic events was 21% with EVAHEART, and 89% with HeartMate II. Serum lactate dehydrogenase was significantly lower with EVAHEART. There was a significantly greater decrease in left ventricular size with HeartMate II. In catheter examination performed 1 month postoperatively, HeartMate II recipients had significantly lower pulmonary capillary wedge pressure and mean pulmonary pressure, despite a comparable cardiac index. Both devices provided excellent clinical results and hemodynamic performance. HeartMate II could be a better choice to avoid driveline infection and neurologic events. Our results suggest that HeartMate II reduced right ventricular afterload. However, further analysis of more cases is required.


Work Hours of Immigrant Versus U.S.-Born Female Workers.
This study was a secondary analysis of cross-sectional data extracted from the 2011-2012 California Health Interview Survey. Data from 8,931 full-time (i.e., 21 hours or more per week) women workers aged 18 to 85 years were analyzed to examine the nature and prevalence of immigrant female workers' work hours, overtime, and related factors in the United States compared to U.S.-born female workers. Results showed that foreign-born female workers did not work longer hours than U.S.-born female workers. Foreign-born female workers who reported poor health worked longer hours than did their U.S.-born counterparts. Foreign-born female workers who were self-employed or worked in family businesses tended to work longer hours than did those women who worked for private companies or nonprofit organizations.


Increasing access and affordability of produce improves perceived consumption of vegetables in low-income seniors.
High cost and limited access to food have been associated with lower intake of fruits and vegetables in limited-income individuals. The Veggie Mobile is a van that carries fresh produce and travels in low-income neighborhoods, selling fruits and vegetables at a fraction of regular supermarket prices. The purpose of this study was to determine whether participation in the Veggie Mobile increases fruit and vegetable intake in a group of seniors. The intervention, buying fruits and vegetables from the Veggie Mobile, was implemented between April and October 2008 in two senior housing sites that had not previously received Veggie Mobile services. Participants were asked about fruit and vegetable intake using a modified six-item questionnaire based on the Behavioral Risk Factor Surveillance System at preintervention and again at 3 to 5 months. The post-survey also included questions about perceived benefits and barriers to using the Veggie Mobile. The two cross-sections of seniors were matched using date of birth. Wilcoxon signed rank test and paired samples t tests examined change in pre- and post-intervention variables. Seventy-nine older adults completed the baseline survey and 63 completed the post-survey. Of these, 43 participants completed both surveys (70% white [n=30], mean age 69 ± 9 years). Mean intake of fruits and vegetables after using the Veggie Mobile increased by 0.37 servings/day. Vegetable intake alone increased from 1.98 ± 1.71 servings/day to 2.58 ± 1.4 servings/day (P=0.027), half of which was potatoes. Change in fruit intake was not significant (P=0.358). At post-intervention, seniors visited the supermarket less often (P=0.001) and spent an average of $14.92 less during their last visit. The majority of participants who completed the post-survey (62 of 63) indicated being satisfied with the program. The Veggie Mobile provides an example of a simple community intervention that has potential to lead to positive behavior change among low-income seniors.


"Mitochondrial Toolbox" - A Review of Online Resources to Explore Mitochondrial Genomics.
Mitochondria play a significant role in many biological systems. There is emerging evidence that differences in the mitochondrial genome may contribute to multiple common diseases, leading to an increasing number of studies exploring mitochondrial genomics. There is often a large amount of complex data generated (for example via next generation sequencing), which requires optimised bioinformatics tools to efficiently and effectively generate robust outcomes from these large datasets. Twenty-four online resources dedicated to mitochondrial genomics were reviewed. This 'mitochondrial toolbox' summary resource will enable researchers to rapidly identify the resource(s) most suitable for their needs. These resources fulfil a variety of functions, with some being highly specialised. No single tool will provide all users with the resources they require; therefore, the most suitable tool will vary between users depending on the nature of the work they aim to carry out. Genetics resources are well established for phylogeny and DNA sequence changes, but further epigenetic and gene expression resources need to be developed for mitochondrial genomics.


Comparative eco-toxicities of nano-ZnO particles under aquatic and aerosol exposure modes.
The antimicrobial activity of ZnO nanoparticles (NPs) was investigated under aquatic and aerosol exposure modes. ZnO NPs in aquatic media aggregated to micrometer-sized particles and did not interact with microorganisms effectively. Hence, the inhibition of microbial growth by nano-ZnO NPs (e.g., Mycobacterium smegmatis and Cyanothece 51142) in aquatic media was mainly attributable to dissolved zinc species. Shewanella oneidensis MR-1 and Escherichia coli were able to produce large amounts of extracellular polymeric substances, and their growth was not inhibited by ZnO NPs in aquatic media, even at high concentrations (>40 mg/L). On the other hand, when ZnO NPs were electrosprayed onto an E. coli biofilm so that NPs could be directly deposited onto the cell surface, the aerosol exposure dramatically reduced cellular viability. For example, an electrospray of ZnO NPs (20 nm) reduced the total number of viable E.coli cells by 57% compared to the control case, in which we electrosprayed only the buffer solution. However, electrospraying large-sized ZnO particles (480 nm) or nonsoluble TiO(2) NPs (20 nm) caused much less lethality to E. coli cells. The above observation implies that the aerosol method of exposing ZnO NPs to biological systems appears to have a much higher antimicrobial activity, and thus may lead to practical applications of employing a novel antimicrobial agent for airborne disease control.


Liquid nitrogen and salicylic/lactic acid paint in the treatment of cutaneous warts in general practice.
Patients with common hand warts and simple plantar warts attending a general practice wart clinic in Northern Ireland were assigned to one of three treatment groups - liquid nitrogen applied weekly, daily application of wart paint (lactic acid one part, salicylic acid one part, collodion four parts), or a combination of the two. Combination therapy cured 87% of common hand warts over a six week period, and was significantly more effective than either agent used separately (P<0.05). The results for simple plantar warts were disappointing and no treatment regimen proved to be significantly better than any other. These treatments were cheap, compliance and tolerance were good, and the six month recurrence rate was minimal. Given the likelihood that warts will multiply if left untreated we would recommend early active treatment for this condition.


Adenoidectomy outcomes in pediatric rhinosinusitis: a meta-analysis.
To evaluate the currently available literature regarding the reported effectiveness of adenoidectomy alone in the management of medically refractory pediatric chronic rhinosinusitis. The MEDLINE and EMBASE databases were systematically searched for English language manuscripts reporting on effectiveness of adenoidectomy alone in management of medically refractory pediatric rhinosinusitis. Additional manuscripts were identified by manual searching. Random effects modeling was performed to produce summary estimates of adenoidectomy effectiveness. Nine studies met the inclusion criteria. Six were cohort studies (level 2b) and four were case series (level 4). Mean sample size was 46 subjects (range = 10-121) with grand mean age of 5.8 years (range 4.4-6.9 years). All studies showed that sinusitis symptoms or outcomes improved in half or more patients after adenoidectomy. Eight studies were sufficiently similar to undergo meta-analysis. The summary estimate of the proportion of patients who significantly improved after adenoidectomy was 69.3% (95% CI = 56.8-81.7%, p < 0.001). The possibility of author bias was explored as one author group contributed a large proportion of patients to the study group. Adenoidectomy reduces caregiver reported symptoms of chronic rhinosinusitis in a majority of pediatric patients. Given its simplicity, low risk profile, and apparent effectiveness, adenoidectomy should be considered first line therapy for medically refractory, uncomplicated pediatric rhinosinusitis.


[Soroepidemiology of Varicella in Brazil - results of a prospective cross-sectional study]
OJECTIVES: Varicella has more serious consequences in adolescents and adults. Recent reports from Europe and Asia show an increasing number of adolescents and young adults being seronegative. As there is only limited data on varicella zoster virus (VZV) seroprevalence in Brazil and to facilitate the strategy for varicella vaccination we conducted a VZV seroprevalence study in Brazil. METHODS: This population-based, cross sectional seroepidemiology study was performed in 4 different regions of Brazil. The studied population was stratified according to gender, age and socioeconomic status. VZV IgG antibodies were analyzed by ELISA. RESULTS: 3,879 subjects aged 1-40 years were included into the study. The overall anti-VZV seropositivity rate across all age groups and centers in Brazil was 85.4%. There was a strong age relationship. Especially in the South East and South seroprevalence was low in the age group 1-5 years (44.5% and 57.8%, respectively) while in the North the rate was 88.9%. Overall, Varicella infection was independent of the socioeconomic level, but in the youngest age groups (1-10 years) seroprevalence rates were significantly lower in the high/medium socioeconomic class for most regions. Clinical history of chickenpox correlates well with anti- VZV seropositivity with a predictive value of 95.1% CONCLUSIONS: In preadolescence a substantial proportion of the Brazilian population is susceptible to Varicella infection, and a considerable part of the adolescents and young adults remain VZVseronegative and are thus also at risk.


Post-transcriptional gene regulation by MAP kinases via AU-rich elements.
Eukaryotic cells must continuously sense their environments, for example their attachment to extracellular matrix and proximity to other cells, differences in temperature or redox conditions, the presence of nutrients, growth factors, hormones, cytokines or pathogens. The information must then be integrated and an appropriate response initiated by modulating the cellular programme of gene expression. The mitogen-activated protein kinase (MAPK) signaling pathways play a critical role in this process. Decades of research have illuminated the many ways in which MAPKs regulate the synthesis of mRNA (transcription) via phosphorylation of transcription factors, cofactors, and other proteins. In recent years it has become increasingly clear that the control of mRNA destruction is equally important for cellular responses to extracellular cues, and is equally subject to regulation by MAPKs. This review will summarize our current understanding of post-transcriptional regulation of gene expression by the MAPKs and the proteins that are involved in this process.


The Newcomb-Benford law in its relation to some common distributions.
An often reported, but nevertheless persistently striking observation, formalized as the Newcomb-Benford law (NBL), is that the frequencies with which the leading digits of numbers occur in a large variety of data are far away from being uniform. Most spectacular seems to be the fact that in many data the leading digit 1 occurs in nearly one third of all cases. Explanations for this uneven distribution of the leading digits were, among others, scale- and base-invariance. Little attention, however, found the interrelation between the distribution of the significant digits and the distribution of the observed variable. It is shown here by simulation that long right-tailed distributions of a random variable are compatible with the NBL, and that for distributions of the ratio of two random variables the fit generally improves. Distributions not putting most mass on small values of the random variable (e.g. symmetric distributions) fail to fit. Hence, the validity of the NBL needs the predominance of small values and, when thinking of real-world data, a majority of small entities. Analyses of data on stock prices, the areas and numbers of inhabitants of countries, and the starting page numbers of papers from a bibliography sustain this conclusion. In all, these findings may help to understand the mechanisms behind the NBL and the conditions needed for its validity. That this law is not only of scientific interest per se, but that, in addition, it has also substantial implications can be seen from those fields where it was suggested to be put into practice. These fields reach from the detection of irregularities in data (e.g. economic fraud) to optimizing the architecture of computers regarding number representation, storage, and round-off errors.


Potentiated gene delivery to tumors using herpes simplex virus/Epstein-Barr virus/RV tribrid amplicon vectors.
The development and use of gene transfer techniques creates an opportunity to achieve better treatment modalities for numerous disease entities. Promising results for treatment in tumor cells in culture and in small animal models have been reported. Nevertheless, the lack of widespread vector distribution throughout tumor tissue is one of the current limitations for successful clinical application of gene therapy paradigms. The use of migratory tumor cells themselves as vector delivery vehicles may allow wider vector distribution in tumors. In addition, continuous release of retrovirus vectors on-site could generate a high local virion concentration over an extended time period with consequent increases in transduction efficiency. In this paper, we present in culture and in vivo data of a herpes simplex virus-Epstein-Barr virus hybrid amplicon vector containing retrovirus vector components (tribrid vector) that allows conversion of tumor cells into retroviral producer cells. With this method, we were able to achieve a local fourfold amplification of stable transgene expression in tumors. The application of this system, which can integrate a transgene cassette into tumors with therapeutic bystander effects, could increase the local amplification effect to a level of clinical relevance.


Important factors determining the nanoscale tracking precision of dynamic microtubule ends.
Tracking dynamic microtubule ends in fluorescence microscopy movies provides insight into the statistical properties of microtubule dynamics and is vital for further analysis that requires knowledge of the trajectories of the microtubule ends. Here we analyse the performance of a previously developed automated microtubule end tracking routine; this has been optimized for comparatively low signal-to-noise image sequences that are characteristic of microscopy movies of dynamic microtubules growing in vitro. Sequences of simulated microtubule images were generated assuming a variety of different experimental conditions. The simulated movies were then tracked and the tracking errors were characterized. We found that the growth characteristics of the microtubules within realistic ranges had a negligible effect on the tracking precision. The fluorophore labelling density, the pixel size of the images, and the exposure times were found to be important parameters limiting the tracking precision which could be explained using concepts of single molecule localization microscopy. The signal-to-noise ratio was found to be a good single predictor of the tracking precision: typical experimental signal-to-noise ratios lead to tracking precisions in the range of tens of nanometres, making the tracking program described here a useful tool for dynamic microtubule end tracking with close to molecular precision.


Targeting surface nucleolin with multivalent HB-19 and related Nucant pseudopeptides results in distinct inhibitory mechanisms depending on the malignant tumor cell type.
Nucleolin expressed at the cell surface is a binding protein for a variety of ligands implicated in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal RGG domain of nucleolin, the HB-19 pseudopeptide, we recently reported that targeting surface nucleolin with HB-19 suppresses progression of established human breast tumor cells in the athymic nude mice, and delays development of spontaneous melanoma in the RET transgenic mice. By the capacity of HB-19 to bind stably surface nucleolin, we purified and identified nucleolin partners at the cell surface. HB-19 and related multivalent Nucant pseudopeptides, that present pentavalently or hexavalently the tripeptide Lysψ(CH2N)-Pro-Arg, were then used to show that targeting surface nucleolin results in distinct inhibitory mechanisms on breast, prostate, colon carcinoma and leukemia cells. Surface nucleolin exists in a 500-kDa protein complex including several other proteins, which we identified by microsequencing as two Wnt related proteins, Ku86 autoantigen, signal recognition particle subunits SRP68/72, the receptor for complement component gC1q-R, and ribosomal proteins S4/S6. Interestingly, some of the surface-nucleolin associated proteins are implicated in cell signaling, tumor cell adhesion, migration, invasion, cell death, autoimmunity, and bacterial infections. Surface nucleolin in the 500-kDa complex is highly stable. Surface nucleolin antagonists, HB-19 and related multivalent Nucant pseudopeptides, exert distinct inhibitory mechanisms depending on the malignant tumor cell type. For example, in epithelial tumor cells they inhibit cell adhesion or spreading and induce reversion of the malignant phenotype (BMC cancer 2010, 10:325) while in leukemia cells they trigger a rapid cell death associated with DNA fragmentation. The fact that these pseudopeptides do not cause cell death in epithelial tumor cells indicates that cell death in leukemia cells is triggered by a specific signaling mechanism, rather than nonspecific cellular injury. Our results suggest that targeting surface nucleolin could change the organization of the 500-kDa complex to interfere with the proper functioning of surface nucleolin and the associated proteins, and thus lead to distinct inhibitory mechanisms. Consequently, HB-19 and related Nucant pseudopeptides provide novel therapeutic opportunities in treatment of a wide variety of cancers and related malignancies.


Mutations of the p53 tumor suppressor gene and ras oncogenes in aflatoxin hepatocarcinogenesis.
Aflatoxin B1 (AFB1) is classified as a group I carcinogen in humans by IARC. However, the exact mechanisms of AFB1 hepatocarcinogenesis have not been fully elucidated. Recent studies have suggested that oncogenes are critical molecular targets for AFB1, and AFB1 causes characteristic genetic changes in the p53 tumor suppressor gene and ras protooncogenes. Up to date, more than 1500 human hepatocellular carcinoma (HCC) samples have been examined for p53 mutations with respect to different AFB1 exposure levels. The most significant finding is that more than 50% of HCC patients from high aflatoxin exposure areas such as southern Africa and Qidong, China harboured a codon 249 G to T transversion in the p53 tumor suppressor gene, which is found to be consistent with the mutagenic specificity of AFB1 observed in vitro. In contrast, this mutational pattern is not found in HCC samples from moderate or low aflatoxin exposure countries or regions. Therefore, this hot-spot mutation is believed to be a molecular fingerprint linking the initial event of AFB1-DNA adduct formation with the ultimate development and progress of human HCC. However, some important points still remain to be explicated. First, in many of these studies, the systematic evaluation of AFB1 exposure is rather limited and the classification of AFB1 exposure level is speculative and confusing, without the definite evidence for the actual aflatoxin exposure level. Second, the role of hepadnaviral infection has to be considered in the induction of this unique mutational spectrum. On the other hand, ras oncogene mutations are frequently found in AFB1-induced HCC samples in experimental animals, while the frequency of ras mutation in human HCC in contrast is much lower than that of p53. Recent studies have provided additional evidence that reactive oxygen species (ROS) and oxidative DNA damage may be involved in AFB1-induced p53 and ras mutations. In future, follow-up cohorts exposed to different levels of AFB1 combined with the determination of putative gene markers are much needed.


Anthropological perspectives on alcohol and drugs at the turn of the new millennium.
This introduction to the collection provides our thoughts on where alcohol and drug studies in anthropology are going as we enter the new millennium. After commenting briefly on each of the papers that comprise the rest of the volume, we discuss what we see as the most important and exciting issues in the future and give our views on what alcohol and drug studies can offer to medical anthropology, anthropology writ large, interdisciplinary and multidisciplinary research, and the realm of public policy and practical affairs. We call for a continued study by anthropologists of the whole array of pharmacologically active substances used by humans in different parts of the world, whether or not such studies are situated within medical anthropology. We note that many of these substances have received little attention from anthropologists to date, quite strikingly so in the cases of substances such as marijuana and methamphetamines. We emphasize that most scholars working in the anthropology of alcohol and drugs are concerned with the application of their findings to social problems, and we note that this has been especially true of research on alcoholic beverages and injection drugs. This leads us to a discussion of anthropology's involvement in public health intervention and policy work in a variety of settings. Such involvement is shown to have informed anthropological theory (notably political economic approaches) and to have enriched the methodological toolkits and forms of data analysis anthropologists use. Perhaps more importantly, we argue that such multidisciplinary involvement in applied work is most likely to eventuate in theoretical progress in alcohol and drug studies, since theory in the social sciences is not bound to singular disciplinary approaches. Thus we advocate for a "hybrid vigor" in this specialty area in the years ahead.


Real-time closed-loop control of human heart rate and blood pressure.
Prolonged bed rest has significant negative impacts on the human body, particularly on the cardiovascular system. To overcome adverse effects and enhance functional recovery in bedridden patients, the goal is to mobilize patients as early as possible while controlling and stabilizing their cardiovascular system. In this paper, we used a robotic tilt table that allows early mobilization by modulating body inclination and automated leg movement to control the cardiovascular variables heart rate (HR) or systolic or diastolic blood pressures (sBP, dBP). The design and use of a control system is often done with a simulation model of a plant, but the time-variant and nonlinear nature of the cardiovascular system and subject-specific responses to external stimuli makes the modeling and identification challenging. Instead, we implemented an intelligent self-learning fuzzy controller that does not need any prior knowledge about the plant. The controller modulates the body inclination in order to adjust the cardiovascular parameters, with leg movement considered as a perturbing factor to the controller. The controller performance was evaluated in six healthy subjects. Measured mean values of HR, sBP, and dBP differed from desired reference values by 1.11 beats/min, 5.10 mmHg, and 2.69 mmHg, respectively. With this new control strategy, HR and dBP could be successfully controlled within medically tolerable ranges (deviations < 2.5 beats/min and < 5 mmHg from desired values, respectively). The control of sBP was less accurate; the results suggest that simultaneous control of multiple input stimuli rather than only adaptive automatic change of the tilt table angle might improve the controllability.


Gestation length, mode of delivery, and neonatal line-thickness variation.
The transition from an intra- to extra-uterine environment leaves its mark in deciduous teeth (and first permanent molars) as an accentuated enamel incremental ring called the neonatal line (NL). This prominent microfeature separates the enamel formed during intrauterine life from that formed after leaving the womb. However, while the physical structure of this scar is well known, the bases of its formation are still a matter of investigation. In particular, besides the influence of the birth-related abrupt environmental and dietary changes and the role played by physiological factors such as hypocalcaemia, a direct relationship between NL thickness variation and the physical was trauma implied by the birth dynamics, the Caesarean, and the operative modes are apparently associated with the thinnest and the thickest lines, respectively. By using the histological record from a deciduous dental sample (exfoliated crowns) of 100 modern healthy school-aged children (47 males and 53 females) of reported birth histories (normal delivery mode: 55 cases; Caesarean: 40; operative: 5), we investigated the relationships between birth dynamics and NL thickness variation. The Tukey Honest Significant Difference method was used to test the differences between the means of the grouping levels. The results of our histo-morphological investigation do not support the suggestion that Caesarean-born children display, on average, a thinner enamel scar compared to children associated to a normal delivery mode. Rather, our study points to the influence exerted by factors intimately related to gestational length variation on the degree of expression of the line.


Olfactory function in Wave 2 of the National Social Life, Health, and Aging Project.
To investigate the sense of smell, including sensitivity and odor identification, and characterize the U.S. national prevalence of olfactory dysfunction in older adults, thereby facilitating further investigation of the substantial risks for older adults associated with this basic sensory ability. The sense of smell was evaluated using the Olfactory Function Field Exam (OFFE), a measure designed specifically for field research, which assesses 3 components of olfaction: sensitivity to n-butanol (a standard testing odorant) and androstadienone (AND, a key social odor produced by humans), as well as the ability to identify odors. Respondents were randomly selected from the National Social Life, Health, and Aging Project Wave 2 sample to receive the OFFE (n = 2,304), and 2,212 consented to participate. In the U.S. population aged 62-90, n-butanol detection ability was significantly worse at older ages (ordinal logistic regression, p < .001); however, there was no difference in detection ability between genders (p = .60). AND detection ability was also significantly worse at older ages (p = .003), but in contrast to n-butanol, women outperformed men (p = .001). As expected, odor identification ability was worse in older people than in younger (p < .001), and women were more accurate than men (p = .001). We report for the first time 3 facets of olfactory function and its association with age and gender in a representative sample of U.S. older adults. Future analyses of these data are needed to elucidate the sense of smell's role in physical, social, and mental health with aging.


Sun, sand, and citizenship: the marketing of gay tourism.
This article investigates trends in the marketing of gay and lesbian tourism. It reviews gay and lesbian travel guides from the 1960s to the 1990s before examining more recent travel materials including brochures and Web sites promoting specific American cities. These promotional materials are a valuable object of inquiry because they are uniquely situated at the intersection of discussions of sexuality, the market, representation, space, and citizenship. Through an aggregate semiotic analysis and ideological criticism, this article examines themes and concerns raised by the recent wave of gay tourism marketing, including questions of visibility, privacy, and assimilation. I argue that while marketers' recent attempts to lure gay and lesbian tourists to specific destinations may seem to suggest increased tolerance and societal inclusion, the specific strategies that they employ actually reveal the second-class citizen status still experienced by gays and lesbians within the rest of American society.


The role of zinc ions in reverse transport mediated by monoamine transporters.
The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2+ binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). Upon binding to this site, Zn2+ causes inhibition of [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) uptake. We investigated the effect of Zn2+ on outward transport by superfusing hDAT-expressing HEK-293 cells preloaded with [3H]MPP+. Although Zn2+ inhibited uptake, Zn2+ facilitated [3H]MPP+ release induced by amphetamine, MPP+, or K+-induced depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET). Mutation of the Zn2+ coordinating residue His(193) to Lys (the corresponding residue in hNET) eliminated the effect of Zn2+ on efflux. Conversely, the reciprocal mutation (K189H) conferred Zn2+ sensitivity to hNET. The intracellular [3H]MPP+ concentration was varied to generate saturation isotherms; these showed that Zn2+ increased V(max) for efflux (rather than K(M-Efflux-intracellular)). Thus, blockage of inward transport by Zn2+ is not due to a simple inhibition of the transporter turnover rate. The observations provide evidence against the model of facilitated exchange-diffusion and support the concept that inward and outward transport represent discrete operational modes of the transporter. In addition, they indicate a physiological role of Zn2+, because Zn2+ also facilitated transport reversal of DAT in rat striatal slices.


Rapid sequencing of individual DNA molecules in graphene nanogaps.
I propose a technique for reading the base sequence of a single DNA molecule using a graphene nanogap to read the DNA's transverse conductance. Because graphene is a single atom thick, single-base resolution of the conductance is readily obtained. The nonlinear current-voltage characteristic is used to determine the base type independent of nanogap-width variations that cause the current to change by 5 orders of magnitude. The expected sequencing error rate is 0% up to a nanogap width of 1.6 nm.


Folded graphene membranes: mapping curvature at the nanoscale.
While the unique elastic properties of monolayer graphene have been extensively investigated, less knowledge has been developed so far on folded graphene. Nevertheless, it has been recently suggested that fold-induced curvature (without in-plane strain) could possibly affect the local chemical and electron transport properties of graphene, envisaging a material-by-design approach where tailored membranes are used in enhanced nanoresonators or nanoelectromechanical devices. In this work we propose a novel method combining apparent strain analysis from high-resolution transmission electron microscopy (HREM) images and theoretical modeling based on continuum elasticity theory and tight-binding atomistic simulations to map and measure the nanoscale curvature of graphene folds and wrinkles. If enough contrast and resolution in HREM images are obtained, this method can be successfully applied to provide a complete nanoscale geometrical and physical picture of 3D structure of various wrinkle and fold configurations.


SU-E-T-22: Is the Residual Range a Universal Quantity to Specify the Quality of Modulated Proton Beams?
To investigate the validity of using the residual range as a universal quantity to specify the quality of modulated proton beams. We used TOPAS (Tool for Particle Simulation), an application of the Geant4 toolkit, to simulate absorbed dose and stopping-power distributions from a commercial passive scattering nozzle. We used the standard physics lists from Geant4 in the simulations. All particles were included, as well as physics models for nuclear interactions. No variance reduction techniques were used. Dose and averaged stopping-power as functions of depth were scored in a water box with 320 scoring volumes of 15 × 15 × 0.1 cm3 . Stopping-power spectra were scored in a15 × 15 × 0.1 cm3 volume located in the middle of SOBPs. All particles were considered in the dose scoring. Only protons (primary and secondary) were considered in the scoring of stopping-power. For the same residual range, differences in averaged stopping-power values of up to 13% were observed for a 200 MeV beam with modulations of 4 cm and 8 cm, respectively. Simulations of four modulated proton energies with the same SOBP of 8 cm showed differences of up to 13% in the averaged stopping-power values even in the SOBP region. We also simulated stopping power spectra in the middle of 8 cm SOBPs for four modulated proton energies. The averaged stopping-power values calculated from the spectra were within 3%, however, their distributions were very different with full width at half-maximum 150% larger for the 250 MeV beam compared to that of the 140 MeV beam. Large differences in the averaged stopping-power values and stopping-power spectra were observed for the same residual range. Determining whether these differences have a significant effect on the response of radiation detectors exposed to proton beams requires further investigation. Natural Sciences and Engineering Research Council of Canada and Ontario Graduate Scholarship Program, Ontario Ministry of Training, Colleges and Universities.


Pharmacological treatment for antipsychotic-related constipation.
Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. Clozapine has been shown to impede gastrointestinal motility, leading to constipation, and has been reported in up to 60% of patients receiving clozapine. In rare cases, complications can be fatal. Appropriate laxatives should be prescribed to treat constipation in people taking antipsychotics, but there is a lack of guidance on the comparative effectiveness and harms of different agents in this population. An understanding of the effectiveness and safety of treatment for antipsychotic-related constipation is important for clinicians and patients alike. To evaluate the effectiveness and safety of pharmacologic treatment (versus placebo or compared against another treatment) for antipsychotic-related constipation (defined as constipated patients of any age, who are treated with antipsychotics, regardless of dose, in which constipation is considered to be an antipsychotic-related side effect). We searched the Cochrane Schizophrenia Group's Trials Register (15 June 2015), which is based on regular searches of MEDLINE, Embase, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records in this register. We also handsearched bibliographies and contacted relevant authors for additional information. We included all published and unpublished randomised controlled trials (RCTs) investigating the efficacy of pharmacological treatments in patients with antipsychotic-related constipation. Pharmacological treatments included laxatives and other medicines that could reasonably be used to combat constipation in this population (e.g. anticholinergic agents, like bethanecol). Two review authors independently extracted data from all included studies and assessed trials for risk of bias. A third author reviewed 20% of trials. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. We discussed any disagreement, documented decisions, and attempted to contact study authors when necessary. We identified two relevant Chinese studies (N = 480) that contributed data to this review. Both studies were over ten years old and poorly reported, lacking descriptions of contemporary CONSORT reporting prerequisites, such as sequence generation, allocation concealment, blinding, participant flow, how the sample size was determined, or how outcomes were measured. The studies also did not report trial registration, pre-specified protocols, consent processes, ethical review, or funding source. We were unsuccessful in making contact with the authors to clarify the missing details. We classified both studies as having an overall high risk of bias.One study compared glycerol suppository with the traditional Chinese medicine (TCM) approaches of tuina massage and acupuncture. Compared to tuina massage, glycerol laxative was less effective in relieving constipation at both two days after treatment (1 RCT; N = 120; RR 2.88, 95% CI 1.89 to 4.39; very low-quality evidence), and three days (1 RCT; N = 120; RR 4.80, CI 1.96 to 11.74, very low-quality evidence). Favourable results were also seen for acupuncture at two days (1 RCT; N = 120; RR 3.50; 95% CI 2.18 to 5.62; very low-quality evidence), and at three days (1 RCT; N = 120; RR 8.00, 95% CI 2.54 to 25.16; very low-quality evidence).The other study compared mannitol, an osmotic laxative, with rhubarb soda or phenolphthalein. Mannitol was more effective than rhubarb soda or phenolphthalein in trelieving constipation within 24 hours of treatment (1 RCT; N = 240; RR 0.07; 95% CI 0.02 to 0.27, very low-quality evidence).No data were reported for our other important outcomes: need for rescue medication, bowel obstruction (a complication of antipsychotic-related constipation), quality of life, adverse events, leaving the study early, and economic costs. We had hoped to find clinically useful evidence appraising the relative merits of the interventions routinely used to manage antipsychotic-related constipation, a common and potentially serious adverse effect of the use of these drugs. The results were disappointing. There were no data comparing the common pharmacological interventions for constipation, such as lactulose, polyethylene glycol, stool softeners, lubricant laxatives, or of novel treatments such as linaclotide. Data available were very poor quality and the trials had a high risk of bias. Data from these biased studies suggested that mannitol, an osmotic laxative, was more effective than rhubarb soda and phenolphthalein in relieving constipation, and a two-week course of glycerol suppositories was less effective than the TCM approaches of tuina massage and acupuncture.Overall, there is insufficient trial-based evidence to assess the effectiveness and safety of pharmacological interventions for treating antipsychotic-related constipation, due to limited, poor quality data (few studies with high risk of bias and no meta-analyses). The methodological limitations in the included studies were obvious, and any conclusions based on their results should be made with caution. Methodologically rigorous RCTs evaluating interventions for treating antipsychotic-related constipation are needed.


The good, the bad, or the useful? The examination of the relationship between the feedback-related negativity (FRN) and long-term learning outcomes.
According to the reinforcement learning account of the error-related negativity (ERN), the ERN is a manifestation of a signal generated in ACC as a consequence of a phasic decrease in the activity of the mesencephalic dopamine system occurring when the monitoring system evaluates events as worse than expected. This signal is also hypothesized to be used to modify behavior to ascertain that future events will have better outcomes. It is therefore expected that this signal be correlated with learning outcomes. We report a study designed to examine the extent to which the ERN is related to learning outcomes within a paired-associates learning task. The feedback-related negativity (FRN) elicited by stimuli that indicated to the participants whether their response was correct or not was examined both according the degree to which the associates were learned in the session and according to whether participants recalled the associations on the next day. The results of the spatio-temporal PCA indicate that, whereas the process giving rise to the negative feedback elicited a FRN whose amplitude was not correlated with long-term learning outcomes, positive feedback was associated with a FRN-like activity, which was correlated with the learning outcomes. Another ERP component that follows the FRN temporally and shares its spatial distribution was found associated with long-term learning outcomes. Our findings shed light on the functional significance of the feedback-related ERP components and are discussed within the framework of the reinforcement learning ERN hypothesis.


Analysis of fatal motor vehicle collisions: evidence from Central Macedonia, Greece.
The objective of this study was to assess the factors associated with the traffic mortality in the region of Central Macedonia in order to produce evidence in building up preventive policies. This study is a descriptive survey covering a three-year period (from 01-01-2006 to 31-12- 2008). The data used were supplied by the regional Road Traffic Police Service in Thessaloniki. A total of 280 fatal vehicle collisions were recorded in three years, in which 312 people died. 266 (85.26%) of the 312 people who died were men and 46 (14.74%) were women. The victims were between 1 and 91 years of age (mean ± SD, 42.00 ± 20.36 years). More fatal vehicle collisions were recorded on weekends and holidays than weekdays. Regarding the type of the vehicle, occupants of two-wheeled motor vehicles were in greater risk for dying compared to heavy duty vehicle passengers, who are considered to be protected by the vehicle. Among the 312 fatalities, alcohol was detected in 87 (28%) of the drivers who were responsible for the collision. Most of them (56/86, 64.4%) were between 15 and 44 years of age. In 6 (1.9%) cases, all of them drivers, illicit substances were detected. Vehicle collisions with younger victims were recorded during the early morning hours, whereas older people died more frequently during daytime. The findings of this study are providing evidence for the design and implementation of concrete and urgently needed preventive strategies in order to control the almost completely preventable fatalities of the road crashes.


Diagnosis of night blindness through standardized interview and electroretinography.
Objective: To compare the diagnosis of NB through the use of the standardized interview of the World Health Organization/Pan American Health Organization (WHO/PAHO) with electroretinography, and also to evaluate the association of these diagnoses with serum concentrations of retinol in class III obesity individuals. Methods: Adult patients of both genders, in the 20-60 age group, with BMI ≥ 40 kg/m² were studied. NB was diagnosed through electroretinography and the standardized interview validated by the WHO/PAHO. Serum level of retinol was quantified by the HPLC-UV method, and VAD was diagnosed when levels were <1.05 µmol /L, and severity was also evaluated. Statistical analysis was carried out through the Statistical Package for the Social Sciences, version 21.0 (p < 0.05). Results: Mean BMI was 44.9  11.8 kg/m², and a negative correlation was found in serum levels of retinol (p= 0.01). The prevalence of VAD, according to the serum concentrations of retinol, was 14%, and of this percentage 23.3% had NB according to the standardized interview, and 22.0% according to electroretinography. NB diagnosed by both methods showed an association with VAD according to the serum concentrations of retinol. Of these individuals with NB, according to the standardized interview, 6.9% showed severe VAD, 10.3% moderate VAD and 82.8% marginal VAD. Conclusion: The standardized interview for the diagnosis of NB can be a good strategy to evaluate the nutritional status of vitamin A, and it is a simple, non-invasive and low-cost method.


Exchange symmetry, fluctuation-compressibility relation, and thermodynamic potentials of quantum liquids.
Liquid helium does not obey the Gibbs fluctuation-compressibility relation, which was noted more than six decades ago. However, still missing is a clear explanation of the reason for the deviation or the correct fluctuation-compressibility relation for the quantum liquid. Here we present the fluctuation-compressibility relation valid for any grand canonical system. Our result shows that the deviation from the Gibbs formula arises from a nonextensive part of thermodynamic potentials. The particle-exchange symmetry of many-body wave function of a strongly degenerate quantum gas is related to the thermodynamic extensivity of the system; a Bose gas does not always obey the Gibbs formula, while a Fermi gas does. Our fluctuation-compressibility relation works for classical systems as well as quantum systems. This work demonstrates that the application range of the Gibbs-Boltzmann statistical thermodynamics can be extended to encompass nonextensive open systems without introducing any postulate other than the principle of equal a priori probability.


Predictors for multiple hospital admissions in children with asthma.
Asthma is one of the most frequent causes of preventable hospital admissions among children. To identify preventable risk factors for future hospital admissions. Some of the environmental and patient characteristics of children who were hospitalized more than once with an acute asthma attack were investigated. An analysis was performed of 140 children with asthma, aged three to 15 years, admitted to the Department of Pediatrics at Dicle University Hospital, Diyarbakir, Turkey, over three years, followed for a maximum of 48 months. Associations between hospital admissions and probable predictors (clinical findings, laboratory studies and a detailed case history) were analyzed. The asthma admissions were higher in boys than in girls (male to female ratio 1.86). Of 140 children, 30 (21.4%) had multiple admissions, defined as a mean of more than one admission per year during the follow-up period. The following factors were associated significantly with the frequency of hospital admission for asthma attacks when analyzed using a Chi2 test: indoor cigarette smoking (odds ratio [OR] 2.55), maternal smoking (OR 4.05), symptoms of dermal atopy (OR 2.96), symptoms of allergic conjunctivitis (OR 2.68), age less than five years (OR 5.12) and use of inhaled corticosteroids during the follow-up (OR 0.37). With multi-variate logistic regression analysis, among other factors, only maternal smoking (r=0.29, P=0.017) and age less than five years (r=-0.32, P=0.012) were significant effective factors for the multiple hospital admissions. No significant association with the frequency of hospital admission was found for sex, serum total immunoglobulin E, history of frequent upper respiratory tract infections or number of family members. Prevention of indoor smoking, especially maternal smoking, may be effective in decreasing hospital admissions in children with asthma. Children less than five years of age are more likely to be hospitalized than are children five years of age or greater.


Drought-induced site-specific DNA methylation and its association with drought tolerance in rice (Oryza sativa L.).
An indica pyramiding line, DK151, and its recurrent parent, IR64, were evaluated under drought stress and non-stress conditions for three consecutive seasons. DK151 showed significantly improved tolerance to drought. The DNA methylation changes in DK151 and IR64 under drought stress and subsequent recovery were assessed using methylation-sensitive amplified polymorphism analysis. Our results indicate that drought-induced genome-wide DNA methylation changes accounted for ∼12.1% of the total site-specific methylation differences in the rice genome. This drought-induced DNA methylation pattern showed three interesting properties. The most important one was its genotypic specificity reflected by large differences in the detected DNA methylation/demethylation sites between DK151 and IR64, which result from introgressed genomic fragments in DK151. Second, most drought-induced methylation/demethylation sites were of two major types distinguished by their reversibility, including 70% of the sites at which drought-induced epigenetic changes were reversed to their original status after recovery, and 29% of sites at which the drought-induced DNA demethylation/methylation changes remain even after recovery. Third, the drought-induced DNA methylation alteration showed a significant level of developmental and tissue specificity. Together, these properties are expected to have contributed greatly to rice response and adaptation to drought stress. Thus, induced epigenetic changes in rice genome can be considered as a very important regulatory mechanism for rice plants to adapt to drought and possibly other environmental stresses.


Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum.
Inflammatory processes and infections of the uterine wall must be accepted as a physiological event in dairy cows after calving. This might result in clinical or subclinical endometritis which is assumed to impair reproductive performance in the current lactation. Several cytokines and acute phase proteins have been discussed as local and systemic mediators of these inflammatory processes. The aim of the present study was to investigate the endometrial mRNA expression of the chemokine CXC ligand 5 (CXCL5), interleukin 1β (IL1B), IL6, IL8, tumour necrosis factor alpha (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2) and haptoglobin (HP) in the postpartum period. Endometrial samples were obtained from primiparous cows (n = 5) on days 10, 17, 24, 31, 38 and 45 postpartum (pp) using the cytobrush technique. Cytological smears were prepared from cytobrush samples to determine the proportion of polymorphonuclear neutrophils (PMN). Total RNA was extracted from endometrial samples, and real-time RT-PCR was performed. A time-dependent mRNA expression of the investigated factors was found for the course of the postpartum period. In detail, a significantly higher expression of these factors was observed on day 17 pp compared to day 31 pp. Furthermore, the proportion of PMN peaked between days 10-24 pp and decreased thereafter to low percentages (< 5%) on day 31 pp and thereafter. In addition, CXCL5, IL1B, IL8 and HP mRNA expression correlated significantly with the proportion of PMN (P < 0.05). A significantly higher CXCL5, IL1B, IL6, IL8, PTGS2 and TNF mRNA content was observed in samples from cows with an inflamed endometrium compared with samples from cows with a healthy endometrium (P < 0.05). These results show that inflammatory cytokines and acute phase proteins are expressed in the bovine endometrium in a time-related manner during the postpartum period, with a significant expression peak on day 17 pp as a possible mucosal immune response in the uterus. The evaluation of the expression patterns of such candidate genes may reveal more information than only determining the percentage of PMN to judge the severity of an inflammation.


Complement activation in sickle cell disease: Dependence on cell density, hemolysis and modulation by hydroxyurea therapy.
The complement system is an innate immune defense cascade that can cause tissue damage when inappropriately activated. Evidence for complement over activation has been reported in small cohorts of patients with sickle cell disease (SCD). However, the mechanism governing complement activation in SCD has not been elucidated. Here, we observe that the plasma concentration of sC5b-9, a reliable marker for terminal complement activation, is increased at steady state in 61% of untreated SCD patients. We show that greater complement activation in vitro is promoted by SCD erythrocytes compared to normal ones, although no significant differences were observed in the regulatory proteins CD35, CD55, and CD59 in whole blood. Complement activation is positively correlated with the percentage of dense sickle cells (DRBCs). The expression levels of CD35, CD55, and CD59 are reduced in DRBCs, suggesting inefficient regulation when cell density increases. Moreover, the surface expression of the complement regulator CD46 on granulocytes was inversely correlated with the plasma sC5b-9. We also show increased complement deposition in cultured human endothelial cells incubated with SCD serum, which is diminished by the addition of the heme scavenger hemopexin. Treatment of SCD patients with hydroxyurea produces substantial reductions in complement activation, measured by sC5b-9 concentration and upregulation of CD46, as well as decreased complement activation on RBCs in vitro. In conclusion, complement over activation is a common pathogenic event in SCD that is associated with formation of DRBCs and hemolysis. And, it affects red cells, leukocytes and endothelial cells. This complement over activation is partly alleviated by hydroxyurea therapy.


Choose wisely: Network, ontology and annotation resources for the analysis of Staphylococcus aureus omics data.
Staphylococcus aureus (S. aureus) is a prominent human and livestock pathogen investigated widely using omic technologies. Critically, due to availability, low visibility or scattered resources, robust network and statistical contextualisation of the resulting data is generally under-represented. Here, we present novel meta-analyses of freely-accessible molecular network and gene ontology annotation information resources for S. aureus omics data interpretation. Furthermore, through the application of the gene ontology annotation resources we demonstrate their value and ability (or lack-there-of) to summarise and statistically interpret the emergent properties of gene expression and protein abundance changes using publically available data. This analysis provides simple metrics for network selection and demonstrates the availability and impact that gene ontology annotation selection can have on the contextualisation of bacterial omics data.


Effects of lead exposure on the expression of phospholipid hydroperoxidase glutathione peroxidase mRNA in the rat brain.
Oxidative damage associated with lead in the brain has been proposed as a possible mechanism of lead toxicity. Of the many antioxidant enzymes, phospholipid hydroperoxidase glutathione peroxidase (PHGPx) is known to protect cells from lipid peroxide-mediated damage by catalyzing lipid peroxide reduction. In this study, the effects of lead on the activity and expression of PHGPx mRNA were investigated in the brains of rats exposed to lead for 8 weeks. Male Sprague-Dawley rats (3 week old, n = 40) were randomly divided into four groups of 10 and treated with four different concentrations of lead in drinking water: a low dose (0.1% lead acetate), a medium dose (0.3% lead acetate), and a high dose (1.0% lead acetate), and a control group (0% lead acetate). We compared the four groups in terms of body and brain weight, lead concentrations in the brain and blood, and the activities of superoxide dismutase (SOD), gluthatione peroxidase (GPx), and PHGPx mRNA in the brain. Phospholipid hydroperoxidase glutathione peroxidase was found to have a dominant role in lead exposure. We also performed in situ hybridization of PHGPx mRNA in the brain to identity PHGPx mRNA active sites. We found that the level of PHGPx mRNA in brain increased in the medium- and low-dose groups, but decreased in the high-dose group versus the non-lead-treated control group. These results suggest that lead exposure increases the expression of PHGPx mRNA in the low- and medium-dose groups without inducing structural changes, and that the reduced expression of PHGPx mRNA in the high-dose group was associated with structural damage. An In situ hybridization study showed that PHGPx mRNA in the brain is expressed mainly in the white matter of the cerebral hemisphere and in the Purkinje cells of the cerebellar hemispheres; these sites are known to be the vulnerable to lead toxicity.


The widespread human desmocollin Dsc2 and tissue-specific patterns of synthesis of various desmocollin subtypes.
By comparison of the cDNA-derived amino acid sequences and the cell type-specific patterns of synthesis we have identified desmocollin Dsc2 as the most widespread, perhaps ubiquitous desmocollin subtype. Using Northern blot analyses and ribonuclease protection assays we have found an approximately 5.6 kb mRNA encoding Dsc2 in all the diverse human tissues, tumors and cell lines examined that are known to possess desmosomes, i.e. not only epithelial cells but also myocardiac cells and lymph nodes. By contrast, desmocollin subtypes Dsc1 and Dsc3 have been detected only in certain stratified squamous epithelia, with the most conspicuous restriction of Dsc1 to epidermis and--remarkably, but unexplained--lymph nodes, and in certain carcinomas and cell lines derived therefrom. We have also determined that both Dsc2 mRNA splice forms, the one encoding the larger polypeptide a and the one coding for the shorter Dsc2b, occur in all the diverse tissues and cell lines examined. We also show that certain cells such as the epidermal keratinocyte line HaCaT and the vulvar carcinoma-derived line A-431 continually synthesize more than one Dsc subtype. The cell type-specific patterns of synthesis of the various Dsg and Dsc subtypes are discussed in relation to tissue development during embryogenesis and to malignant transformations, and the utilization of reagents for the specific Dsg and Dsc subtypes in tumor diagnosis is proposed.


Molecular localization of a ribosome-dependent ATPase on Escherichia coli ribosomes.
We have previously isolated and described an Escherichia coli ribosome-bound ATPase, RbbA, that is required for protein synthesis in the presence of ATP, GTP and the elongation factors, EF-Tu and EF-G. The gene encoding RbbA, yhih, has been cloned and the deduced protein sequence harbors two ATP-motifs and one RNA-binding motif and is homologous to the fungal EF-3. Here, we describe the isolation and assay of a truncated form of the RbbA protein that is stable to overproduction and purification. Chemical protection results show that the truncated RbbA specifically protects nucleotide A937 on the 30S subunit of ribosomes, and the protected site occurs at the E-site where the tRNA is ejected upon A-site occupation. Other weakly protected bases in the region occur at or near the mRNA binding site. Using radiolabeled tRNAs, we study the stimulating effect of this truncated RbbA on the binding and release of different tRNAs bound to the (aminoacyl) A-, (peptidyl) P- and (exit) E-sites of 70S ribosomes. The combined data suggest plausible mechanisms for the function of RbbA in translation.


An immunoregulatory role for neutrophils in CD4+ T helper subset selection in mice with candidiasis.
Granulocytes may serve immunoregulatory and effector roles in different limbs of the immune response to infection. Using live vaccine strain or virulent challenge in mucosal or systemic infection of mice with Candida albicans, we examined the effect of mAb-mediated depletion of neutrophils on the course of primary and secondary challenge and on development of CD4+ cell-dependent immunity. We obtained evidence of deleterious effects of neutrophil depletion occurring at the time of infection under all conditions of testing, both in naive and in previously immunized mice. In contrast, neutrophil depletion appeared to benefit the hosts late in the course of an overwhelming systemic infection. In an attempt to correlate neutrophil function with the nature of the T cell response, we tested the ability of neutrophils to produce cytokines associated with functionally distinct CD4+ Th cell responses to Candida. We found that neutrophils were endowed with the capacity to secrete IL-12 and IL-10 in vitro in response to the yeast. Neutrophil ablation early in the course of Th1-associated, self-limiting infection appeared to change the qualitative development of the T cell response, and rendered mice susceptible to infection. In addition to long recognized contributions to acute anti-candidal responses, these data suggest an important role for neutrophils both in initiation and in expression of Candida-specific immunity.


Risk factor analysis of kyphotic malalignment after cervical intramedullary tumor resection in adults.
OBJECTIVE A number of studies have reported that surgery for cervical intramedullary tumors via the posterior approach can result in postoperative sagittal malalignment of the cervical spine; however, the risk factors remain unclear. The purpose of this study was to investigate the changes in cervical spinal alignment after surgery for cervical intramedullary tumors in adults and to elucidate the risk factors for cervical spinal sagittal misalignment. METHODS Data for the period from April 2001 to December 2011 for all adults who had undergone surgery for cervical intramedullary spinal cord tumors at a single institution were retrospectively analyzed to determine the postoperative changes in cervical spine alignment. Patients younger than 20 years of age and those who required postoperative radiotherapy were excluded from the study. Patients were divided into 2 groups according to tumor location: upper tumor (U) group, in which the central region of the tumor was above the C-5 level; and lower tumor (L) group, in which the central region of the tumor was at or below the C-5 level. Changes in alignment of the cervical spine were measured on plain lateral radiographs. Data on atrophy of the deep extensor muscles (DEMs), tumor location, detachment of the DEMs from the C-2 spinous process, the C2-7 angle before surgery, patient age at surgery, tumor histology, patient sex, tumor size, and number of laminae affected were reviewed for each patient, and the correlation of each of these factors with cervical spinal malalignment was evaluated using statistical analysis. RESULTS The 54 adults eligible for analysis had a mean age of 49.1 years. Ependymoma was the most common cervical intramedullary tumor (63.0%) in this series. In the tumor location U group, the kyphotic angle of the C2-7 spinal segments increased after surgery (-5.8° ± 2.8°). In contrast, in the L group, the C2-7 lordotic angle increased after surgery (6.4° ± 2.6°). In the univariate analysis, atrophy of the DEMs, detachment of the DEMs from the C-2 spinous process, and an upper cervical location of the tumor were identified as factors significantly correlated with the development of cervical spinal kyphosis after surgery. Multiple linear regression analysis revealed the following as risk factors for kyphotic change of the cervical spine after surgery: 1) atrophy of the DEMs after surgery (β = -0.54, p < 0.01), and 2) detachment of the DEMs from the C-2 spinous process (β = -0.37, p < 0.01). CONCLUSIONS Atrophy of the DEMs after surgery and detachment of the DEMs from the C-2 spinous process are directly related to the risk of cervical spinal kyphosis after surgery for cervical intramedullary tumors in adults. Therefore, preservation of the DEMs, especially those attached to the C-2 spinous process, is important for the prevention of kyphotic malalignment of the cervical spine after surgery for intramedullary tumors.


Salivary Heparanase Level Is a Potential Biomarker to Diagnose and Prognose the Malignant Salivary Gland Tumor.
Upregulation of heparanase has been reported in an increasing number of human cancer tissues. However, the level of salivary heparanase and its clinical significance in patients with salivary gland tumors remain unclear. Salivary heparanase levels in patients with salivary gland tumors were detected using enzyme-linked immunosorbent assays (ELISAs) and the clinical significance was evaluated by analyzing the correlations among salivary heparanase levels, clinicopathological parameters, and clinical outcomes. The levels of salivary heparanase were significantly higher in patients with malignant salivary gland tumors than in benign tumors and normal controls (P<0.0001). High salivary heparanase levels were positively correlated with increased lymph node metastasis (P = 0.0235) and poorer tumor node metastasis stage (TNM) (P = 0.0183). Survival analyses revealed that high salivary heparanase levels were associated with worse overall survival (P = 0.0023) and disease-free survival (DFS) (P = 0.0025). The study shows that salivary heparanase levels, as detected by the ELISAs, can be used to diagnose and provide an accurate prognosis for malignant salivary gland tumors. Salivary heparanase level was an independent predictor in patients with malignant salivary gland tumors.


Infrared target tracking with kernel-based performance metric and eigenvalue-based similarity measure.
An infrared target tracking framework is presented that consists of three main parts: mean shift tracking, its tracking performance evaluation, and position correction. The mean shift tracking algorithm, which is a widely used kernel-based method, has been developed for the initial tracking for its efficiency and effectiveness. A performance evaluation module is applied for the online evaluation of its tracking performance with a kernel- based metric to unify the tracking and performance metric within a kernel-based tracking framework. Then the tracking performance evaluation result is input into a controller in which a decision is made whether to trigger a position correction process. The position correction module employs a matching method with a new eigenvalue-based similarity measure computed from a local complexity degree weighted covariance matrix. Experimental results on real-life infrared image sequences are presented to demonstrate the efficacy of the proposed method.


Studying Early Decision Making with Progressive Bar Charts.
We conduct a user study to quantify and compare user performance for a value comparison task using four bar chart designs, where the bars show the mean values of data loaded progressively and updated every second (progressive bar charts). Progressive visualization divides different stages of the visualization pipeline-data loading, processing, and visualization-into iterative animated steps to limit the latency when loading large amounts of data. An animated visualization appearing quickly, unfolding, and getting more accurate with time, enables users to make early decisions. However, intermediate mean estimates are computed only on partial data and may not have time to converge to the true means, potentially misleading users and resulting in incorrect decisions. To address this issue, we propose two new designs visualizing the history of values in progressive bar charts, in addition to the use of confidence intervals. We comparatively study four progressive bar chart designs: with/without confidence intervals, and using near-history representation with/without confidence intervals, on three realistic data distributions. We evaluate user performance based on the percentage of correct answers (accuracy), response time, and user confidence. Our results show that, overall, users can make early and accurate decisions with 92% accuracy using only 18% of the data, regardless of the design. We find that our proposed bar chart design with only near-history is comparable to bar charts with only confidence intervals in performance, and the qualitative feedback we received indicates a preference for designs with history.


Identification of urine metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine following consumption of a single cooked chicken meal in humans.
Many studies suggest that mutagenic/carcinogenic chemicals in the diet, like 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), may play a role in human cancer initiation. We have developed a method to quantify PhIP metabolites in human urine and have applied it to samples from female volunteers who had eaten a meal of cooked chicken. For this analysis, urine samples (5 ml) were spiked with a deuterium-labeled internal standard, adsorbed to a macroporous polymeric column and then eluted with methanol. After a solvent exchange to 0.01 M HCl, the urine extracts were passed through a filter, applied to a benzenesulfonic acid column, washed with methanol/acid and eluted with ammonium acetate and concentrated on a C(18) column. The metabolites were eluted from the C(18) column and quantified by LC/MS/MS. In our studies of human PhIP metabolism, eight volunteers were fed 200 g of cooked chicken containing a total of 27 microg PhIP. Urine samples were collected for 24 h after the meal, in 6 h aliquots. Although no metabolites could be found in urine collected from volunteers before eating the chicken, four major human PhIP metabolites, N:(2)-OH-PhIP-N:(2)-glucuronide, PhIP-N:(2)-glucuronide, 4'-PhIP-sulfate and N:(2)-OH-PhIP-N:3-glucuronide, were found in the urine after the chicken meal. The volunteers in the study excreted 4-53% of the ingested PhIP dose in the urine. The rate of metabolite excretion varied among the subjects, however, in all of the subjects the majority of the metabolites were excreted in the first 12 h. Very little metabolite was detected in the urine after 18 h. In humans, N:(2)-OH-PhIP-N:(2) glucuronide is the most abundant urinary metabolite, followed by PhIP-N:(2)-glucuronide. The variation seen in the total amount, excretion time and metabolite ratios with our method suggests that individual digestion, metabolism and/or other components of the diet may influence the absorption and amounts of metabolic products produced from PhIP.