Host-plant selectivity of rhizobacteria in a crop/weed model system.
Belowground microorganisms are known to influence plants' performance by altering the soil environment. Plant pathogens such as cyanide-producing strains of the rhizobacterium Pseudomonas may show strong host-plant selectivity. We analyzed interactions between different host plants and Pseudomonas strains and tested if these can be linked to the cyanide sensitivity of host plants, the cyanide production of bacterial strains or the plant identity from which strains had been isolated. Eight strains (four cyanide producing) were isolated from roots of four weed species and then re-inoculated on the four weed and two additional crop species. Bacterial strain composition varied strongly among the four weed species. Although all six plant species showed different reductions in root growth when cyanide was artificially applied to seedlings, they were generally not negatively affected by inoculation with cyanide-producing bacterial strains. We found a highly significant plant species x bacterial strain interaction. Partitioning this interaction into contrasts showed that it was entirely due to a strongly negative effect of a bacterial strain (Pseudomonas kilonensis/brassicacearum, isolated from Galium mollugo) on Echinochloa crus-galli. This exotic weed may not have become adapted to the bacterial strain isolated from a native weed. Our findings suggest that host-specific rhizobacteria hold some promise as biological weed-control agents.


Guideline-indicated treatments and diagnostics, GRACE risk score, and survival for non-ST elevation myocardial infarction.
To investigate whether improved survival from non-ST-elevation myocardial infarction (NSTEMI), according to GRACE risk score, was associated with guideline-indicated treatments and diagnostics, and persisted after hospital discharge. National cohort study (n = 389 507 patients, n = 232 hospitals, MINAP registry), 2003-2013. The primary outcome was adjusted all-cause survival estimated using flexible parametric survival modelling with time-varying covariates. Optimal care was defined as the receipt of all eligible treatments and was inversely related to risk status (defined by the GRACE risk score): 25.6% in low, 18.6% in intermediate, and 11.5% in high-risk NSTEMI. At 30 days, the use of optimal care was associated with improved survival among high [adjusted hazard ratio (aHR) -0.66 95% confidence interval (CI) 0.53-0.86, difference in absolute mortality rate (AMR) per 100 patients (AMR/100-0.19 95% CI -0.29 to -0.08)], and intermediate (aHR = 0.74, 95% CI 0.62-0.92; AMR/100 = -0.15, 95% CI -0.23 to -0.08) risk NSTEMI. At the end of follow-up (8.4 years, median 2.3 years), the significant association between the use of all eligible guideline-indicated treatments and improved survival remained only for high-risk NSTEMI (aHR = 0.66, 95% CI 0.50-0.96; AMR/100 = -0.03, 95% CI -0.06 to -0.01). For low-risk NSTEMI, there was no association between the use of optimal care and improved survival at 30 days (aHR = 0.92, 95% CI 0.69-1.38) and at 8.4 years (aHR = 0.71, 95% CI 0.39-3.74). Optimal use of guideline-indicated care for NSTEMI was associated with greater survival gains with increasing GRACE risk, but its use decreased with increasing GRACE risk.


The importance of life cycle concepts for the development of safe nanoproducts.
Whilst the global players in industry are rapidly moving forward to take advantage of the new opportunities and prospects offered by nanotechnologies, it is imperative that such developments take place in a safe and sustainable manner. The increasing use of engineered nanomaterials (ENMs) in consumer products has raised certain concerns over their safety to human health and the environment. There are currently a number of major uncertainties and knowledge gaps in regard to behavior, chemical and biological interactions and toxicological properties of ENMs. As dealing with these uncertainties will require the generation of new basic knowledge, it is unlikely that they will be resolved in the immediate future. One has to consider the whole life cycle of nanoproducts to ensure that possible impacts can be systematically discovered. For example, life cycle assessment (LCA) - a formalized life cycle concept - may be used to assess the relative environmental sustainability performance of nanoproducts in comparison with their conventional equivalents. Other less formalized life cycle concepts in the framework of prospective technology assessment may uncover further detailed and prospective knowledge for human and environmental exposure to ENMs during the life cycle of nanoproducts. They systematically reveal impacts such as cross product contamination or dissipation of scarce materials among others. The combination of different life cycle concepts with the evolving knowledge from toxicology and risk assessment can mitigate uncertainties and can provide an early basis for informed decision making by the industry and regulators.


Age differences in the enjoyment of incongruity-resolution and nonsense humor during adulthood.
This study tested a model of the development of incongruity-resolution and nonsense humor during adulthood. Subjects were 4,292 14- to 66-year-old Germans. Twenty jokes and cartoons representing structure-based humor categories of incongruity resolution and nonsense were rated for funniness and aversiveness. Humor structure preferences were also assessed with a direct comparison task. The results generally confirmed the hypotheses. Incongruity-resolution humor increased in funniness and nonsense humor decreased in funniness among progressively older subjects after the late teens. Aversiveness of both forms of humor generally decreased over the ages sampled. Age differences in humor appreciation were strongly correlated with age differences in conservatism. An especially strong parallel was found between age differences in appreciation of incongruity-resolution humor and age differences in conservatism.


Deciphering Adaptation Strategies of the Epidemic Clostridium difficile 027 Strain during Infection through In Vivo Transcriptional Analysis.
Clostridium difficile is responsible for a wide spectrum of infection from asymptomatic carriage to severe, relapsing colitis. Since 2003, C. difficile infections have increased with a higher morbidity and mortality due to the emergence of epidemic and hypervirulent C. difficile strains such as those of the epidemic lineage 027/BI/NAP1. To decipher the hypervirulence and epidemicity of 027 strains, we analyzed gene expression profiles of the R20291 027 strain using a monoxenic mouse model during the first 38h of infection. A total of 741 genes were differentially expressed during the course of infection. They are mainly distributed in functional categories involved in host adaptation. Several genes of PTS and ABC transporters were significantly regulated during the infection, underlying the ability of strain R20291 to adapt its metabolism according to nutrient availability in the digestive tract. In this animal model, despite the early sporulation process, sporulation efficiency seems to indicate that growth of R20291 vegetative cells versus spores were favored during infection. The bacterial mechanisms associated to adaptability and flexibility within the gut environment, in addition to the virulence factor expression and antibiotic resistance, should contribute to the epidemicity and hypervirulence of the C. difficile 027 strains.


Range accuracy of photon heterodyne detection with laser pulse based on Geiger-mode APD.
In this paper, we propose a combined system of heterodyne detection with laser pulse and photon counting based on Geiger-mode avalanche photodiode (GM-APD) that is designed to achieve the range of remote non-cooperative target. Based on the heterodyne principle and assuming that the creation of primary electrons in GM-APD is Poisson-distributed, the range accuracy model is established. The factors that influence the range accuracy, namely pulse width, echo intensity, local oscillator (LO) intensity, noise, echo position, and beat frequency, are discussed. The results show that these six factors have significant influence on the range accuracy when the echo intensity is extremely weak. In case that the primary electrons of the echo signal are beyond 4, the pulse width and echo intensity are the main influence factors. It is also shown that the stronger echo intensity, narrower pulse width, low noise, large echo position, and small beat frequency produce higher range accuracy in a pulsed photon heterodyne detection system based on GM-APD.


Sample registration of vital events with verbal autopsy: a renewed commitment to measuring and monitoring vital statistics.
Registration of births, recording deaths by age, sex and cause, and calculating mortality levels and differentials are fundamental to evidence-based health policy, monitoring and evaluation. Yet few of the countries with the greatest need for these data have functioning systems to produce them despite legislation providing for the establishment and maintenance of vital registration. Sample vital registration (SVR), when applied in conjunction with validated verbal autopsy procedures and implemented in a nationally representative sample of population clusters represents an affordable, cost-effective, and sustainable short- and medium-term solution to this problem. SVR complements other information sources by producing age-, sex-, and cause-specific mortality data that are more complete and continuous than those currently available. The tools and methods employed in an SVR system, however, are imperfect and require rigorous validation and continuous quality assurance; sampling strategies for SVR are also still evolving. Nonetheless, interest in establishing SVR is rapidly growing in Africa and Asia. Better systems for reporting and recording data on vital events will be sustainable only if developed hand-in-hand with existing health information strategies at the national and district levels; governance structures; and agendas for social research and development monitoring. If the global community wishes to have mortality measurements 5 or 10 years hence, the foundation stones of SVR must be laid today.


Cardiorespiratory fitness and oxidative stress: effect of acute maximal aerobic exercise in children and adolescents.
Evaluate the effects of oxidative stress in saliva in young males, according to their cardiorespiratory fitness and taking acute maximal aerobic exercise into consideration. An incremental exercise test (20 meter shuttle run) was used. Seventy healthy male subjects, aged 10 to 14 years, were included in the study and were classified into two groups according to fitness parameters. Subjects were expected to take the 20 meter shuttle run test. Group I had high cardiorespiratory fitness while group II had low cardiorespiratory fitness below the mean for their age. Saliva samples were taken before and immediately after exercise in order to measure levels of reduced glutathione, lipoperoxides, glutathione/lipoperoxides ratio and catalase. The values of reduced glutathione were significantly diminished regardless the subjects' cardiorespiratory fitness. The glutathione/lipoperoxides ratio was significantly diminished in group I. In addition, positive correlations were observed between lipoperoxides values after the 20 meter shuttle run test. High cardiorespiratory fitness does not seem to be an essential factor effecting in the oxidative stress values before exercise. However, oxidative stress could be greater with more intensity and duration after and acute maximal physical exercise.


A cross-sectional study of aggression levels in physicians and orthopaedic surgeons: impact on specialty selection and training?
To determine if current validated psychometric evaluations could determine a difference in basic behavioural characteristics between surgical and medical specialties. Cross-sectional study. Two district general hospitals and one University teaching hospital in England, UK. Internal medicine (16) and trauma and orthopaedic (20) consultants. Aggression levels as assessed by the Buss and Warren questionnaire. The self-administered questionnaire assesses aggression in terms of physical, verbal, anger, hostility, indirect hostility and an overall assessment of aggression. All participants had aggression scores below the population average. We found a significant difference (P < 0.01) in total level of aggression, with orthopaedic consultants scoring a mean of 61.1 (standard deviation [SD] 9.2) and physicians 51.3 (SD 9.5). When analysis of the five different subtypes of aggression was carried out, orthopaedic surgeons scored significantly higher in terms of verbal aggression (P = 0.005), hostility (P = 0.002) and indirect hostility (P = 0.03). This study joins a growing evidence base for aspects of behaviour indicative of a given specialty. Aggression is a relatively stable behavioural characteristic from adolescence, and as such this is the first study of its type to suggest that the differences in behavioural characteristics seen between specialties are inherent, rather than learned. It is unclear if the differences observed represent an attraction of that specialty to the personality type or is required for success within the given specialty. Whether this can be used in terms of selection into higher specialty training, or influence training within specialties, requires further work.


Diverse microbial communities hosted by the model carnivorous pitcher plant Sarracenia purpurea: analysis of both bacterial and eukaryotic composition across distinct host plant populations.
The pitcher plant Sarracenia purpurea supplements nutrient acquisition through carnivory, capturing insect prey which are digested by a food web community of eukaryotes and bacteria. While the food web invertebrates are well studied, and some recent studies have characterized bacteria, detailed genetic analysis of eukaryotic diversity is lacking. This study aimed to compare eukaryotic and bacterial composition and diversity of pitcher communities within and between populations of host plants in nearby but distinct wetland habitats, and to characterize microbial functions across populations and in comparison with another freshwater community. Pitcher fluid was sampled from the two wetlands, Cedarburg and Sapa Bogs, community DNA was extracted, and 16S and 18S rRNA amplicons were sequenced and data processed for community-level comparisons. Bacterial diversity in the small pitcher volume rivaled that of larger aquatic communities. Between pitcher plant populations, several bacterial families (Kiloniellaceae, Acetobacteraceae, Xanthobacteraceae, Sanguibacteraceae, Oligoflexaceae, Nitrosomonadaceae, Chromatiaceae, Saprospiraceae) were significantly higher in one population. However, although predicted pitcher bacterial functions were distinct from other freshwater communities, especially for some amino acid metabolism, functions were similar across all the pitchers in the two populations. This suggests some functional redundancy among bacterial taxa, and that functions converge to achieve similar food web processes. The sequencing identified a previously under-appreciated high diversity of ciliates, Acari mites, fungi and flagellates in pitcher communities; the most abundant sequences from eukaryotic taxa were Oligohymenophorea ciliates, millipedes and Ichthyosporea flagellates. Two thirds of taxa were identified as food web inhabitants and less than one third as prey organisms. Although eukaryotic composition was not significantly different between populations, there were different species of core taxonomic groups present in different pitchers-these differences may be driven by wetland habitats providing different populations to colonize new pitchers. Eukaryotic composition was more variable than bacterial composition, and there was a poor relationship between bacterial and eukaryotic composition within individual pitchers, suggesting that colonization by eukaryotes may be more stochastic than for bacteria, and bacterial recruitment to pitchers may involve factors other than prey capture and colonization by eukaryotic food web inhabitants.


Differences in the response of inbred mouse strains to the factor increasing monocytopoiesis.
Previous studies have shown that monocyte production during an inflammatory response is controlled by the factor increasing monocytopoiesis (FIM), secreted by macrophages at the site of inflammation. The inflammatory reaction to latex particles and a saline-soluble extract of Listeria monocytogenes (SEL), expressed as the number of monocytes in the circulation and of macrophages at the site of inflammation, was about twice as strong in C57BL/10 mice compared with CBA mice. This raised the question as to the mechanism underlying these differences. One possibility might be that these mouse strains differ with respect to the production of FIM, but this cannot be the case because the maximum levels of FIM activity in the serum of both C57BL/10 and CBA mice given latex or SEL intraperitoneally were almost the same; however, the courses of FIM activity in the two strains after intraperitoneal latex were not exactly synchronous. Another possibility is that the sensitivity of monocyte precursor cells for FIM differs. Evidence for the latter was provided by the finding that the intravenous injection of sera with FIM activity obtained from C57BL/10 and from CBA mice into the C57BL/10 mice evoked monocytosis, whereas CBA mice did not respond to these sera. Earlier studies showed that an increase of monocytes after the injection of serum containing FIM reflects increased monocyte production. Taken together, the results of the present study demonstrate that one of the mechanisms underlying the genetic control of the inflammatory response is, rather than enhanced FIM synthesis, the ability of monocyte precursors in the bone marrow to respond to FIM by increased monocyte production.


Amino acid transporters in the regulation of human skeletal muscle protein metabolism.
To highlight recent research on amino acid sensing and signaling and the role of amino acid transporters in the regulation of human skeletal muscle protein metabolism. The mechanisms that sense amino acid availability and activate mechanistic target of rapamycin complex 1 signaling and protein synthesis are emerging, with multiple new proteins and intracellular amino acid sensors recently identified. Amino acid transporters have a role in the delivery of amino acids to these intracellular sensors and new findings provide further support for amino acid transporters as possible extracellular amino acid sensors. There is growing evidence in human skeletal muscle that amino acid transporter expression is dynamic and responsive to various stimuli, indicating amino acid transporters may have a unique role in the regulation of human skeletal muscle adaptation. There is a clear need to further examine the role of amino acid transporters in human skeletal muscle and their link to cellular amino acid sensing and signaling in the control of protein metabolism. A better understanding of amino acid transport and transporters will allow us to optimize nutritional strategies to accelerate muscle health and improve outcomes for clinical populations.


Effects of mountain biking versus hiking on trails under different environmental conditions.
Recreational use of nature areas is increasing worldwide. All trail-based activities have a certain degradation effect on vegetation and soil, and conflicts between conservation values and recreation may occur. Controversy still exists regarding the relative impact of mountain bikers compared to hikers on trails. In this study, we manipulated the use intensity from hikers and mountain bikers on existing, natural-surfaced trails, and investigated effects of increased use and the relative importance of mountain biking on trail degradation. In two study sites, two trails were selected, one designated for hiking and one for biking. Passes were counted with TRAFx counters. The proportion of mountain bikers on the designated biking trails was on average 47%, and on the hiking trails 13%. Trail width and depth were recorded at permanently marked transects repeatedly throughout the growing season, and analyzed with linear mixed models as a function of number of passes, proportion of bikers and environmental conditions along the trail. Trail width, both the core trail without vegetation and the total area influenced by trampling and biking, showed on average small, but highly variable increases with enhanced use. Trail widening occurred particularly in moist parts, and trail width increased more when a larger proportion of the passes was mountain bikers. Trail depth did not change much throughout the study period, suggesting that the soils along the trails were already compacted and to a limited degree prone to soil movement and subsequent soil loss. Our study shows that on-trail use by hikers and mountain bikers have relatively limited overall effects in terms of trail widening and deepening, but that effects depend highly on environmental conditions; enhanced use of trails in wet areas is likely to result in greater trail degradation, and more so if a large proportion of the users are mountain bikers. Management and maintenance of trails, in terms of re-routing or trail surface hardening, could thus be necessary to avoid negative impacts of increased use. For such management actions to be successful, they need to be targeted towards the actual user groups and the natural conditions in the area.


Tuberculosis and HIV in the Caribbean: approaches to diagnosis, treatment, and prophylaxis.
In the Caribbean region, the lifetime risk of active tuberculosis (TB) in purified protein derivative (PPD)-positive HIV-infected patients is 50%. Screening of individuals with cough who came to an HIV voluntary counseling and testing center in Haiti revealed active TB in 33% of patients. TB prophylaxis is effective in preventing active disease in HIV-infected individuals, and secondary prophylaxis has been shown to reduce recurrence in patients diagnosed with TB at more advanced stages of immunosuppression. Recommendations for anti-TB therapy differ according to whether antiretroviral therapy is available or not and according to whether the TB diagnosis is made while the patient is receiving antiretroviral therapy or not. This article summarizes a presentation by Jean William Pape, MD, at the first CHART Caribbean Conference on the Clinical Management of HIV/AIDS in Montego Bay, Jamaica in June 2004.


Community Health Worker Employer Survey: Perspectives on CHW Workforce Development in the Midwest.
A statewide Community Health Worker Employer Survey was administered to various clinical, community, and faith-based organizations (n = 240) across a range of rural and urban settings in the Midwest. At least 80% of participants agreed or strongly agreed that items characterized as supervisory support were present in their work environment. Thirty-six percent of respondents currently employed CHWs, over half (51%) of survey respondents reported seeing the need to hire/work with more CHWs, and 44% saw the need for CHWs increasing in the future. Regarding CHW support, a majority of respondents indicated networking opportunities (63%), paid time for networking (80%), adequate time for supervision (75%), orientation training (78%), mandatory training (78%), ongoing training (79%), and paid time for training (82%). Open-ended responses to the question "In your organization, what needs could CHWs meet?" resulted in the largest number of respondents reporting mental health issues as a priority, followed by connecting people with services or resources, educating the public on preventive health, family support, and home care/visitations. Our findings suggest that respondents, who largely have supervisory or managerial roles, view workplace environments in Nebraska favorably, despite the fact that nearly two-thirds of respondents typically work well over 40 h per week. In addition, CHWs could help address mental and physical health needs in a variety of community and clinical settings through primary and secondary prevention activities, such as provision of health screenings, health and nutrition education, connecting people to resources and empowering community members through these activities and more.


Rapid method for screening dried blood samples on filter paper for human immunodeficiency virus type 1 DNA.
PCR is a highly sensitive method for the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in blood mononuclear cells and plasma. However, blood separation techniques require extensive laboratory support systems and are difficult when a limited volume of blood is available, which is often the case for infants. The use of blood samples stored on filter paper has many advantages for the detection of perinatal HIV-1 infection, but current methods require extraction and purification of target DNA prior to PCR amplification. We report a highly sensitive and rapid method for the extraction and detection of HIV-1 DNA in infant blood samples stored on filter papers. Because this rapid protocol does not involve steps for the removal of potential inhibitors of the PCR, the highest sensitivity is achieved by testing the filter paper lysate in quadruplicate. Assays for HIV-1 DNA were done by using nested PCR techniques that amplify HIV-1 gag DNA from blood spot samples on filter paper and from corresponding viably frozen mononuclear cells separated from venous blood samples obtained from 111 infants born to HIV-1-seropositive mothers. PCR results with blood from filter papers showed 100% specificity (95% confidence internal [CI] 93.1 to 100%) and 96% (95% CI, 88.65 to 98.9%) and 88% (95% CI, 79.2 to 94.5%) sensitivity (for quadruplicate and duplicate tests, respectively) compared to PCR results with blood mononuclear cells. Moreover, this method could detect HIV-1 sequences of multiple subtypes.


Angiotensin II regulates the metabolism but not the secretion of vasoactive intestinal peptide in the rabbit.
1. We have previously demonstrated that the metabolism and secretion of vasoactive intestinal peptide are affected by both acute and chronic dietary sodium. Sodium concentrations in portal and systemic plasma were unaffected by differing levels of sodium intake or administration of an acute gastric sodium load. We sought, therefore, to determine whether other hormones involved in sodium homoeostasis (such as angiotensin II) might be involved in regulating the metabolism and secretion of vasoactive intestinal peptide. We determined the metabolic clearance rate and theoretical secretion rate of vasoactive intestinal peptide in rabbits on low sodium (high circulating angiotensin II) and high sodium (low circulating angiotensin II) diets with and without simultaneous angiotensin II infusion. 2. The metabolic clearance rate of vasoactive intestinal peptide was significantly higher in rabbits on the high sodium diet during both vehicle control (P < 0.01) and angiotensin II (P < 0.05) infusion. Angiotensin II infusion decreased the metabolism of vasoactive intestinal peptide in rabbits on both low (P < 0.01) and high (P < 0.01) sodium diets. 3. Although there was a significant difference in secretion rates between the two dietary groups (P < 0.025) under basal conditions, infusion of angiotensin II did not alter the secretion rate significantly in either group. 4. We conclude that angiotensin II regulates the metabolism of vasoactive intestinal peptide in the rabbit, but does not regulate its secretion.


Cumulative lead exposure in relation to mortality and lung cancer morbidity in a cohort of primary smelter workers.
The purpose of this study was to determine the mortality and cancer incidence of long-term lead smelter workers at a primary smelter. A cohort of 3979 workers employed for at least 1 year during 1928-1979 and a subcohort of 1992 workers employed in lead-exposed departments (lead only workers) was formed. The expected mortality in 1955-1987 and cancer incidence in 1958-1987 were calculated relative to the county rates, specified for cause, gender, 5-year age groups, and calendar year. A cumulative blood-lead index was used for the dose-response analyses. The lung cancer incidence of the total cohort [standardized incidence ratio (SIR) 2.8, 95% confidence interval (95% CI) 2.1-3.8] and the group with the highest exposure (SIR 3.1, 95% CI 2.0-4.6) was high. Similar risk estimates were observed with a latency of 15 years. The workers hired before 1950 had higher lung cancer risk estimates (SIR 3.6, 95% CI 2.6-5.0) than the workers hired later (SIR 1.3, 95% CI 0.6-2.6, no latency period). The risk estimates for lung cancer were further elevated in the subcohort of lead-only workers (SIR 5.1, 95% CI 2.0-10.5 in the highest exposed subgroup; latency period of 15 years). No excesses of other malignancies were noted. The increased relative risks were probably mainly due to interactions between lead and other carcinogenic exposures, including arsenic. Further study is required concerning such possible interactions before a role in the induction of lung cancer can be ascribed to lead.


Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).
Fractal analysis of the retinal vasculature provides a global measure of the complexity and density of retinal vessels summarised as a single variable: the fractal dimension. We investigated fractal dimensions as long-term predictors of microvasculopathy in type 1 diabetes. We included 180 patients with type 1 diabetes in a 16 year follow-up study. In baseline retinal photographs (from 1995), all vessels in a zone 0.5-2.0 disc diameters from the disc margin were traced using Singapore Institute Vessel Assessment-Fractal image analysis software. Artefacts were removed by a certified grader, and fractal dimensions were calculated using the box-counting method. At follow-up (in 2011), diabetic neuropathy, nephropathy and proliferative retinopathy were assessed and related to baseline fractal dimensions in multiple regressions adjusted for sex and baseline age, diabetes duration, HbA1c, BP, BMI, vibration perception threshold, albuminuria, retinopathy and vessel diameters. Mean baseline age and diabetes duration were 21.0 and 13.4 years, respectively, and of patients 50.0% were males. The mean fractal dimension was 1.3817. The 16 year incidences of neuropathy, nephropathy and proliferative retinopathy were 10.8%, 8.0% and 27.9%, respectively. Multiple regression analyses showed a lower fractal dimension to significantly predict incident neuropathy (OR 1.17 per 0.01 fractal dimension decrease [95% CI 1.01, 1.36]), nephropathy (OR 1.40 per 0.01 fractal dimension decrease [95% CI 1.10, 1.79]) and proliferative retinopathy (OR 1.22 per 0.01 fractal dimension decrease [95% CI 1.09, 1.37]). The retinal vascular fractal dimension is a shared biomarker of diabetic microvasculopathy, thus indicating a possible common pathogenic pathway. Retinal fractal analysis therefore is a potential tool for risk stratification in type 1 diabetes.


Study of placing a second intravenous line in trauma.
We evaluated the benefit of emergency medical services providers' placing a second intravenous (IV) line in the prehospital trauma setting. Our hypothesis was that the placement of a second IV catheter in trauma does not result in an improvement in heart rate, blood pressure, rehospitalizaton rate, or 30-day mortality. A retrospective chart review of 320 trauma patients in a one-year period was conducted at our level I trauma center. All trauma patients who had vascular access obtained prehospitally were included. Patients with two IV lines received an average of 348.4 mL more fluid (95% confidence interval [CI]: 235.6, 461.1; p < 0.0001). No change in heart rate, pulse oximetry, Glasgow Coma Scale score, systolic blood pressure, rehospitalization rate, or 30-day mortality was noted. These effects persisted for patients who were initially tachycardic (heart rate 3.92 bpm; 95% CI ?3.01, 10.82; p = 0.27) or hypotensive (blood pressure 22.00 mmHg; 95% CI ?4.17, 48.16; p = 0.10). Redundant prehospital IV lines provided no noticeable benefit in physiologic support for trauma patients. When controlling for confounding variables, no significant outcome difference was noted, even in the hypotensive patients. The traditional approach for establishment of a secondary IV line in prehospital trauma patients should not be followed in a dogmatic fashion.


Metacoder: An R package for visualization and manipulation of community taxonomic diversity data.
Community-level data, the type generated by an increasing number of metabarcoding studies, is often graphed as stacked bar charts or pie graphs that use color to represent taxa. These graph types do not convey the hierarchical structure of taxonomic classifications and are limited by the use of color for categories. As an alternative, we developed metacoder, an R package for easily parsing, manipulating, and graphing publication-ready plots of hierarchical data. Metacoder includes a dynamic and flexible function that can parse most text-based formats that contain taxonomic classifications, taxon names, taxon identifiers, or sequence identifiers. Metacoder can then subset, sample, and order this parsed data using a set of intuitive functions that take into account the hierarchical nature of the data. Finally, an extremely flexible plotting function enables quantitative representation of up to 4 arbitrary statistics simultaneously in a tree format by mapping statistics to the color and size of tree nodes and edges. Metacoder also allows exploration of barcode primer bias by integrating functions to run digital PCR. Although it has been designed for data from metabarcoding research, metacoder can easily be applied to any data that has a hierarchical component such as gene ontology or geographic location data. Our package complements currently available tools for community analysis and is provided open source with an extensive online user manual.


Preservation of key biomolecules in the fossil record: current knowledge and future challenges.
We have developed a model based on the analyses of modern and Pleistocene eggshells and mammalian bones which can be used to understand the preservation of amino acids and other important biomolecules such as DNA in fossil specimens. The model is based on the following series of diagenetic reactions and processes involving amino acids: the hydrolysis of proteins and the subsequent loss of hydrolysis products from the fossil matrix with increasing geologic age; the racemization of amino acids which produces totally racemized amino acids in 10(5)-10(6) years in most environments on the Earth; the introduction of contaminants into the fossil that lowers the enantiomeric (D:L) ratios produced via racemization; and the condensation reactions between amino acids, as well as other compounds with primary amino groups, and sugars which yield humic acid-like polymers. This model was used to evaluate whether useful amino acid and DNA sequence information is preserved in a variety of human, amber-entombed insect and dinosaur specimens. Most skeletal remains of evolutionary interest with respect to the origin of modern humans are unlikely to preserve useful biomolecular information although those from high latitude sites may be an exception. Amber-entombed insects contain well-preserved unracemized amino acids, apparently because of the anhydrous nature of the amber matrix, and thus may contain DNA fragments which have retained meaningful genetic information. Dinosaur specimens contain mainly exogenous amino acids, although traces of endogenous amino acids may be present in some cases. Future ancient biomolecule research which takes advantage of new methologies involving, for example, humic acid cleaving reagents and microchip-based DNA-protein detection and sequencing, along with investigations of very slow biomolecule diagenetic reactions such as the racemization of isoleucine at the beta-carbon, will lead to further enhancements of our understanding of biomolecule preservation in the fossil record.


Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency.
Chronic venous insufficiency (CVI) affects a large number of people in Western countries, and is responsible for considerable inconvenience, discomfort, suffering, and costs. Micronized purified flavonoid fraction (MPFF, 450 mg diosmin plus 50 mg hesperidin-Daflon 500 mg) is a potent venotropic drug used in the treatment of venous insufficiency. Pharmacological and clinical studies demonstrated the comprehensive mode of action of Daflon 500 mg: it increases venous tone, it improves lymph drainage, and it protects the microcirculation. Clinical international, prospective, multicenter, randomized, controlled studies versus placebo studies documenting the effects of Daflon 500 mg in CVI at advanced stages with edema, skin changes, and venous leg ulcer are reviewed. In edema, one of the most frequent complaints of patients, Daflon 500 mg brings about a significant reduction in leg circumference, thanks to its capacity to inhibit inflammatory reactions and to decrease capillary hyperpermeability. The rationale for the use of Daflon 500 mg for treatment of skin disorders and venous leg ulcer is its action on the microcirculation-damaging processes. Regarding skin changes, Daflon 500 mg has been shown to improve venous trophic disorders, like gravitational (stasis) dermatitis, and dermatofibrosclerosis. In venous leg ulcer, Daflon 500 mg's clinical efficacy has been demonstrated in addition to standard treatment or versus standard treatment alone. Daflon 500 mg, thanks to its comprehensive mode of action on the veins, lymphatics, and microcirculation, is the method of choice not only in the early stages of CVI treatment, but also in the severe stages of this condition, in combination with compression treatment, sclerotherapy, and surgery if appropriate.


Post-Discharge Care Duration, Charges, and Outcomes Among Medicare Patients After Primary Total Hip and Knee Arthroplasty.
In April 2016, the U.S. Centers for Medicare & Medicaid Services initiated mandatory 90-day bundled payments for total hip and knee arthroplasty for much of the country. Our goal was to determine duration of care, 90-day charges, and readmission rates by discharge disposition and U.S. region after hip or knee arthroplasty. Using the 2008 Medicare Provider Analysis and Review database 100% sample, we identified patients who had undergone elective primary total hip or knee arthroplasty. We collected data on patient age, sex, comorbidities, U.S. Census region, discharge disposition, duration of care, 90-day charges, and readmission. Multivariate regression was used to assess factors associated with readmission (logistic) and charges (linear). Significance was set at p < 0.01. Patients undergoing 138,842 total hip arthroplasties were discharged to home (18%), home health care (34%), extended-care facilities (35%), and inpatient rehabilitation (13%); patients undergoing 329,233 total knee arthroplasties were discharged to home (21%), home health care (38%), extended-care facilities (31%), and inpatient rehabilitation (10%). Patients in the Northeast were more likely to be discharged to extended-care facilities or inpatient rehabilitation than patients in other regions. Patients in the West had the highest 90-day charges. Approximately 70% of patients were discharged home from extended-care facilities, whereas after inpatient rehabilitation, >50% of patients received home health care. Among those discharged to home, 90-day readmission rates were highest in the South (9.6%) for patients undergoing total hip arthroplasty and in the Midwest (8.7%) and the South (8.5%) for patients undergoing total knee arthroplasty. Having ≥4 comorbidities, followed by discharge to inpatient rehabilitation or an extended-care facility, had the strongest associations with readmission, whereas the region of the West and the discharge disposition to inpatient rehabilitation had the strongest association with higher charges. Among Medicare patients, discharge disposition and number of comorbidities were most strongly associated with readmission. Inpatient rehabilitation and the West region had the strongest associations with higher charges. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Using the Oxford Cognitive Screen to Detect Cognitive Impairment in Stroke Patients: A Comparison with the Mini-Mental State Examination.
The Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive deficits after stroke. The scale consists of 10 tasks encompassing five cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive deficits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients. The present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine performance on the OCS as a function of subtypes of cerebral infarction and clinical severity. 325 first stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classification and NIHSS, were given according to standard procedures. About a third of patients (35.3%) had a performance lower than the cutoff (<22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories. Overall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive deficits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive profiling.


Propolis organogel as a novel topical delivery system for treating wounds.
Propolis has traditionally been used in curing infections and healing wounds and burns. The aim of this study is to formulate pluronic lecithin organogel of propolis to improve its availability and antimicrobial activity. Different organogels were prepared by using soybean lecithin, isopropyl palmitate, pluronic F127 and water. The effect of quantity of lecithin and pluronic F127 and percentage of oil phase was investigated. The organogels were evaluated for appearance, texture, pH, drug content and viscosity. In vitro release studies were carried out using cellophane membrane. Drug permeation through abdominal rat skin from organogels that showed high % drug release was compared to that from propolis suspension in distilled water. Finally, the antimicrobial activity of the selected propolis formulation against different bacterial isolates was compared with that of propolis suspension in water. Results showed that all organogel formulations except the formula containing 10% pluronic F127, showed acceptable physical properties. Drug content of organogel formulations was in the range of 97.5-100.2%. The pH of the formulations was in the range of 5.5-6.3 that suits the skin pH, indicating skin compatibility. The viscosity was in the range of 5366-8984 cp. A significant decrease in drug release from formulations was observed with increase in concentration of lecithin and pluronic F127. Decreasing oil phase percentage to 20% w/w led to a decrease in drug release from the formulation. The formula containing 3% lecithin and 20% pluronic F127 exhibited superior skin permeation and antimicrobial activity over propolis suspension in water.


Mirth, laughter and gelastic seizures.
Little is known about what pathways subserve mirth and its expression laughter. We present three patients with gelastic seizures and laughter elicited by electrical stimulation of the cortex who provide some insight into the mechanisms of laughter and its emotional concomitants. The first patient had seizures manifested by laughter without a subjective feeling of mirth. Magnetic resonance imaging showed a cavernous haemangioma in the left superior mesial frontal region. Ictal subdural electrode recording showed the seizure onset to be in the left anterior cingulate gyrus. Removal of the lesion and of the seizure focus rendered the patient virtually seizure free over 16 months of follow-up. The other two patients had complex partial seizures of temporal lobe origin. Electrical stimulation of the fusiform gyrus and parahippocampal gyrus produced bursts of laughter accompanied by a feeling of mirth. These cases reveal a high likelihood of cingulate and basal temporal cortex contribution to laughter and mirth in humans, and suggest the possibility that the anterior cingulate region is involved in the motor act of laughter, while the basal temporal cortex is involved in processing of laughter's emotional content in man.


Extreme Risk Protection Orders Intended to Prevent Mass Shootings: A Case Series.
Urgent, individualized interventions to reduce firearm access, such as extreme risk protection orders (ERPOs, colloquially known as "red flag" orders), provide a rapid, focused response when risk for imminent firearm violence is high. Studies to date suggest such interventions are most commonly used to prevent suicide and are effective. Authorizing legislation has often been enacted after public mass shootings but, to our knowledge, there have been only 2 reported cases of ERPO use in efforts to prevent mass shootings. California enacted the nation's first ERPO statute, which took effect in January 2016. The authors are evaluating that statute's implementation and effectiveness and are seeking to obtain court records for all 414 cases occurring in 2016 to 2018. Based on 159 records received thus far, this article presents an aggregate summary and individual histories for a preliminary series of 21 cases in which ERPOs were used in efforts to prevent mass shootings. Most subjects were male and non-Hispanic white; the mean age was 35 years. Most subjects made explicit threats and owned firearms. Four cases arose primarily in relation to medical or mental health conditions, and such conditions were noted in 4 others. Fifty-two firearms were recovered. As of early August 2019, none of the threatened shootings had occurred, and no other homicides or suicides by persons subject to the orders were identified. It is impossible to know whether violence would have occurred had ERPOs not been issued, and the authors make no claim of a causal relationship. Nonetheless, the cases suggest that this urgent, individualized intervention can play a role in efforts to prevent mass shootings, in health care settings and elsewhere. Further evaluation would be helpful.


Home or foster home care versus institutional long-term care for functionally dependent older people.
Changing population demographics have led to an increasing number of functionally dependent older people who require care and medical treatment. In many countries, government policy aims to shift resources into the community from institutional care settings with the expectation that this will reduce costs and improve the quality of care compared. To assess the effects of long-term home or foster home care versus institutional care for functionally dependent older people. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE, Embase, CINAHL, and two trials registers to November 2015. We included randomised and non-randomised trials, controlled before-after studies and interrupted time series studies complying with the EPOC study design criteria and comparing the effects of long-term home care versus institutional care for functionally dependent older people. Two reviewers independently extracted data and assessed the risk of bias of each included study. We reported the results narratively, as the substantial heterogeneity across studies meant that meta-analysis was not appropriate. We included 10 studies involving 16,377 participants, all of which were conducted in high income countries. Included studies compared community-based care with institutional care (care homes). The sample size ranged from 98 to 11,803 (median N = 204). There was substantial heterogeneity in the healthcare context, interventions studied, and outcomes assessed. One study was a randomised trial (N = 112); other included studies used designs that had potential for bias, particularly due lack of randomisation, baseline imbalances, and non-blinded outcome assessment. Most studies did not select (or exclude) participants for any specific disease state, with the exception of one study that only included patients if they had a stroke. All studies had methodological limitations, so readers should interpret results with caution.It is uncertain whether long-term home care compared to nursing home care decreases mortality risk (2 studies, N = 314, very-low certainty evidence). Estimates ranged from a nearly three-fold increased risk of mortality in the homecare group (risk ratio (RR) 2.89, 95% confidence interval (CI) 1.57 to 5.32) to a 62% relative reduction (RR 0.38, 95% CI 0.17 to 0.61). We did not pool data due to the high degree of heterogeneity (I2 = 94%).It is uncertain whether the intervention has a beneficial effect on physical function, as the certainty of evidence is very low (5 studies, N = 1295). Two studies reported that participants who received long-term home care had improved activities of daily living compared to those in a nursing home, whereas a third study reported that all participants performed equally on physical function.It is uncertain whether long-term home care improves happiness compared to nursing home care (RR 1.97, 95% CI 1.27 to 3.04) or general satisfaction because the certainty of evidence was very low (2 studies, N = 114).The extent to which long-term home care was associated to more or fewer adverse health outcomes than nursing home care was not reported.It is uncertain whether long-term home care compared to nursing home care decreases the risk of hospital admission (very low-certainty evidence, N = 14,853). RR estimates ranged from 2.75 (95% CI 2.59 to 2.92), showing an increased risk for those receiving care at home, to 0.82 (95% CI 0.72 to 0.93), showing a slightly reduced risk for the same group. We did not pool data due to the high degree of heterogeneity (I2 = 99%). There are insufficient high-quality published data to support any particular model of care for functionally dependent older people. Community-based care was not consistently beneficial across all the included studies; there were some data suggesting that community-based care may be associated with improved quality of life and physical function compared to institutional care. However, community alternatives to institutional care may be associated with increased risk of hospitalisation. Future studies should assess healthcare utilisation, perform economic analysis, and consider caregiver burden.


Lessons from the study of T-cell differentiation in persistent human virus infection.
Confusion surrounds the current classification of memory and effector T-cell subsets and there is a lack of consistency in the use of these terms between human and murine studies. The development of peptide-HLA tetrameric complexes ("tetramers") that accurately identify virus-specific T cells and can be used with a range of cell surface and intra-cellular markers has provided further insights in our understanding of the process of T-cell differentiation, or post-thymic development. We propose that T-cell differentiation subsets in human viral infection should be regarded as distinct from the current definitions of memory and effector cells; further work is needed to reveal the role of the differentiation process in anti-viral immunity.


The effect of aquatic plant abundance on shell crushing resistance in a freshwater snail.
Most of the shell material in snails is composed of calcium carbonate but the organic shell matrix determines the properties of calcium carbonate crystals. It has been shown that the deposition of calcium carbonate is affected by the ingestion of organic compounds. We hypothesize that organic compounds not synthesized by the snails are important for shell strength and must be obtained from the diet. We tested this idea indirectly by evaluating whether the abundance of the organic matter that snails eat is related to the strength of their shells. We measured shell crushing resistance in the snail Mexipyrgus churinceanus and the abundance of the most common aquatic macrophyte, the water lily Nymphaea ampla, in ten bodies of water in the valley of Cuatro Ciénegas, Mexico. We used stable isotopes to test the assumption that these snails feed on water lily organic matter. We also measured other factors that can affect crushing resistance, such as the density of crushing predators, snail density, water pH, and the concentration of calcium and phosphorus in the water. The isotope analysis suggested that snails assimilate water lily organic matter that is metabolized by sediment bacteria. The variable that best explained the variation in crushing resistance found among sites was the local abundance of water lilies. We propose that the local amount of water lily organic matter provides organic compounds important in shell biomineralization, thus determining crushing resistance. Hence, we propose that a third trophic level could be important in the coevolution of snail defensive traits and predatory structures.


Cost and determinants of morbidity from work related disabling injuries in Taiwan.
To estimate the cost and determinants of morbidity from work related disabilities. 114 people who lived in metropolitan Taipei and who had received disability compensation from the Labor Insurance Bureau from March to June, 1991 were randomly selected. There were 77 workers interviewed through a questionnaire that inquired about possible loss of productivity including the duration of morbidity, the ability to return to work, and any change in monthly income upon returning to work. The mean (SD) duration of a stay in hospital was 29 (39) days, median: 15 days. The average duration between discharge from the hospital and returning to work was 111 (146) days, median: 45 days. The main determinants of the duration of the stay in hospital were the number of stays in hospital and the severity of the injury. A multivariate linear analysis showed that old age and the severity of injury determine the durations of morbidity. An ordinal logistic regression analysis showed that the severity of injury, size of the factory, and age determined the magnitude of future productivity loss. Based on these models, it was estimated that the total duration of morbidity (in hospital and at home) due to occupational disability was 660,000 person-days each year. When the percentage of the decrease in income because of permanent disability was converted into a loss of work days, the annual morbidity costs were about 19,000-26,000 person-years between 1985-1990. The morbidity cost was about five times as high as the lump sum payment that a worker usually received for disability compensation. We conclude that morbidity cost should be evaluated carefully in the future for the establishment of accurate and fair disability compensation payments.


The Cumulative Incidence of Self-Reported Suicide-Related Thoughts and Attempts in Young Canadians.
To estimate the cumulative incidence of self-reported suicide-related thoughts (SRTs) and suicide attempts (SAs) in males and females from 11 to 25 years of age in Canada. A cohort study was conducted by linking cycles 2 to 8 from the National Longitudinal Survey of Children and Youth, a representative survey of Canadians aged 11 to 25 years conducted from 1996 to 2009. The 11- to 25-year cumulative incidence of self-reported SRTs and SAs (with suicidal intent) was estimated in males and females using a novel application of a counting process approach to account for discontinuous risk intervals between survey cycles. The risk of SRTs was 29% (95% confidence interval [CI], 26% to 31%) in females and 19% (95% CI, 16% to 23%) in males. The risk of SAs was 16% (95% CI, 14% to 19%) in females and 7% (95% CI, 6% to 8%) in males. Over 70% of SRTs and SAs first occur between 11 and 16 years of age and 30% between 11 and 13 years of age, respectively. The risk of SRTs and SAs is high in young Canadians, with most events first occurring in early to mid-adolescence and possibly earlier. Females are at a higher risk compared to males. This research underscores the need for better longitudinal surveillance of SRTs and SAs in the population. A counting process framework could be useful for future research using existing longitudinal surveys suffering from design limitations relating to gaps in respondent follow-up. Furthermore, these findings have implications for younger SRT and SA risk management by clinicians and earlier implementation of suicide prevention programs.


Monoclonal anti-idiotopic antibodies against myasthenia-inducing anti-acetylcholine receptor monoclonal antibodies. Preponderance of nonparatope-directed antibodies affecting antigen binding.
To analyze components of the idiotypic network in experimental autoimmune disease, we produced 17 isogeneic anti-idiotopic monoclonal antibodies (anti-Id) against two experimental autoimmune myasthenia gravis-producing anti-acetylcholine receptor (anti-AChR) monoclonal antibodies. We studied the binding of five of the anti-Id to the anti-AChR monoclonal antibodies bearing the complementary idiotopes (Id-mAb). They bound with Kd values ranging from 0.06 to 0.86 nM, values comparable to those of Id-mAb:AChR complexes (0.26 and 0.34 nM). All of the anti-Id tested moderately inhibited the binding of AChR to Id-mAb, whereas for each anti-Id, AChR either strongly inhibited anti-Id binding or had no effect on anti-Id binding. Hence, the inhibition of Id-mAb:AChR binding by anti-Id was not reciprocal with the inhibition of anti-Id:Id-mAb binding by AChR. For each anti-Id, the relative affinities of anti-Id and AChR for Id-mAb together with the lack of symmetry of inhibition by anti-Id compared to inhibition by AChR indicate that these two "ligands" are not competitive inhibitors. Consequently, anti-Id and AChR do not bind to overlapping sites on the Id-mAb, suggesting that the observed inhibition is mediated allosterically. This may be a common mechanism of anti-Id:Id binding, which would have important implications for the mechanism of anti-Id-induced suppression.


Insights from molecular dynamics simulations for computational protein design.
A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.


SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress.
Forkhead transcription factor, DAF-16, regulates genes that contribute both to longevity and resistance to various stresses in C. elegans. We and others have reported that members of the FOXO, mammalian homologs of DAF-16, also regulate genes related to stress resistance, such as GADD45. The NAD-dependent protein deacetylase, SIR2, is required for life span extension in yeast induced by caloric restriction, which also increases longevity in a wide variety of other organisms, including mammals. Sir2.1, a homolog of yeast SIR2, also extends life span by acting in a DAF-16 signaling pathway in C. elegans. We demonstrate that mammalian SIRT1 (Sir2alpha) physiologically interacts with FOXO. Acetylation of FOXO4, by the transcriptional coactivator p300, counteracted transcriptional activation of FOXO4 by p300. In contrast, mammalian SIRT1 was found to bind to FOXO4, catalyze its deacetylation in an NAD-dependent manner, and thereby increase its transactivation activity. The activity of FOXO4 is suppressed or enhanced by SIRT1 inhibitor, nicotinamide, or its activator, resveratrol, respectively. In response to oxidative stress, FOXO accumulates within the nucleus and induces GADD45 expression. FOXO-mediated GADD45 induction is markedly impaired in the cell, which depleted SIRT1 expression by RNA-interference. These results indicate that mammalian SIRT1 plays a pivotal role for FOXO function via NAD-dependent deacetylation in response to oxidative stress, and thereby may contribute to cellular stress resistance and longevity.


Evaluation of the Nitrite Test in Screening for Urinary Tract Infection in Febrile Children with Sickle Cell Anaemia in Maiduguri- Nigeria.
BACKGROUND: Urinary tract infection is a significant cause of morbidity in children with sickle cell anaemia (SCA). Individuals with SCA have increased risk of urinary tract infection (UTI). Facilities for urine culture may not be available in most rural and even some urban areas in most developing countries like Nigeria. It will therefore be useful to have a simple means of screening such children for UTI with the intent of prompt treatment. MATERIALS AND METHODS: The study will evaluate the usefulness of the nitrite test in detecting UTI in febrile SCA children. This study was carried out in the Department of Paediatrics University of Maiduguri Teaching Hospital and State Specialist Hospital Maiduguri. RESULTS: The study consisted of 250 children aged 6 months to 15 years with SCA presenting with fever (temperature ≥ 37. 5°C). Midstream urine specimen was collected from older children and suprapubic bladder aspiration of urine specimen was collected from infants. Samples were subjected to nitrite test, culture and sensitivity. There was significant bacteriuria in 65 (26+) children with SCA. A positive test for nitrite was obtained in 43 of the 65 (66.2+) children. The nitrite test has a specificity of 93.5+ in detecting bacteriuria, a sensitivity of 66.2+, a positive predictive value of 78.2+ and a negative predictive value of 93.5+. A positive nitrite test was significantly associated with bacteriuria, while a negative test was also significantly associated with an absence of bacteriuria. CONCLUSIONS: From this study, the nitrite test is useful as a screening test for UTI in SCA children. However in sick children with SCA, microscopy, culture and sensitivity should still be done in spite of a negative nitrite test.


Interleukin-2 as a predictor of early postoperative atrial fibrillation after cardiopulmonary bypass graft (CABG).
Recently, inflammation has been considered as a risk factor of postoperative atrial fibrillation (PAF). The main purpose of this study was to estimate the connections between occurrence of PAF and cytokine release. Thirty-three patients who qualified for cardiopulmonary bypass graft (CABG) were included in the study. Blood was taken from all of them before CABG, then 3 h, 24 h, and 72 h afterwards. Cytokine (IL-6, IL-2, IL-4, IL-10, IFN-gamma, TNF-alpha) concentration was measured at every time point. Eleven patients developed atrial fibrillation after the CABG. Five of them developed PAF until 1 day post-CABG and six of them after 1 day post-CABG. Patients who developed PAF before 1 day post-CABG were characterized by a higher level of IL-2 in sera before 24 h and 72 h post-CABG compared with patients without PAF. Moreover, the PAF before 1 day post-CABG group was also characterized by the higher level of IFN-gamma and IL-10 at 24 h after intervention. Analysis of patients who developed PAF after 1 day post-CABG revealed a higher level of IL-10 and IFN-gamma at 24 h post-CABG compared with patients without PAF. In this study, we have shown for the first time a straightforward connection between IL-2 sera levels and the development of PAF shortly after CABG.


Microstructural characterization of normal and malignant human prostate tissue with vascular, extracellular, and restricted diffusion for cytometry in tumours magnetic resonance imaging.
The aim of this study was to demonstrate the feasibility of the recently introduced Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours (VERDICT) framework for imaging prostate cancer with diffusion-weighted magnetic resonance imaging (DW-MRI) within a clinical setting. The VERDICT framework is a noninvasive microstructure imaging technique that combines an in-depth diffusion MRI acquisition with a mathematical model to estimate and map microstructural tissue parameters such as cell size and density and vascular perfusion. In total, 8 patients underwent 3-T MRI using 9 different b values (100-3000 s/mm). All patients were imaged before undergoing biopsy. Experiments with VERDICT analyzed DW-MRI data from patients with histologically confirmed prostate cancer in areas of cancerous and benign peripheral zone tissue. For comparison, we also fitted commonly used diffusion models such as the apparent diffusion coefficient (ADC), the intravoxel incoherent motion (IVIM), and the kurtosis model. We also investigated correlations of ADC and kurtosis with VERDICT parameters to gain some biophysical insight into the various parameter values. Eight patients had prostate cancer in the peripheral zone, with Gleason score 3 + 3 (n = 1), 3 + 4 (n = 6), and 4 + 3 (n = 1). The VERDICT model identified a significant increase in the intracellular and vascular volume fraction estimates in cancerous compared with benign peripheral zone, as well as a significant decrease in the volume of the extracellular-extravascular space (EES) (P = 0.05). This is in agreement with manual segmentation of the biopsies for prostate tissue component analysis, which found proliferation of epithelium, loss of surrounding stroma, and an increase in vasculature. The standard ADC and kurtosis parameters were also significantly different (P = 0.05) between tissue types. There was no significant difference in any of the IVIM parameters (P = 0.11 to 0.29). The VERDICT parametric maps from voxel-by-voxel fitting clearly differentiated cancer from benign regions. Kurtosis and ADC parameters correlated most strongly with VERDICT's intracellular volume fraction but also moderately with the EES and vascular fractions. The VERDICT model distinguished tumor from benign areas, while revealing differences in microstructure descriptors such as cellular, vascular, and EES fractions. The parameters of ADC and kurtosis models also discriminated between cancer and benign regions. However, VERDICT provides more specific information that disentangles the various microstructural features underlying the changes in ADC and kurtosis. These results highlight the clinical potential of the VERDICT framework and motivate the construction of a shorter, clinically viable imaging protocol to enable larger trials leading to widespread translation of the method.


Morphologic differences of the endocardial electrogram in beats of sinus and ventricular origin.
The lack of accurate arrhythmia detection and identification is one of the major obstacles to improvement in the efficacy of antitachycardia devices. We evaluated a method for detection of beats of ventricular origin compared to sinus rhythm based on the morphology of the endocardial electrogram. In order to compare mechanically induced ventricular beats to normal sinus beats, endocardial electrograms from a standard pacing electrode were recorded from eight open-chested dogs. Time and frequency domain features analyzed included peak-to-peak amplitude (AMP), maximal slew rate (dV/dT), and frequency content (-3 dB downpoint). Quantitative morphologic comparison of the waveforms was performed using standard correlation and by the absolute area of difference between the waveform and a sinus beat template. The AMP and dV/dT for a group of ventricular beats did not differ significantly from beats of sinus origin. In the unipolar configuration -3 dB for ventricular beats was significantly different from sinus beats (p = .01), but overlap occurred in three of eight cases. Conversely, using either method of assessment of morphological differences, all ventricular beats could be identified without overlapping the values for normal beats. We concluded that morphologic analysis of the endocardial electrogram by such methods may be a highly accurate means of distinguishing between beats of sinus and ventricular origins. This technique may also be applicable to the problem of automatic rhythm identification by implanted devices.


Seasonal pattern of pneumonia mortality among under-five children in Nairobi's informal settlements.
Using longitudinal data from the Nairobi Urban and Demographic Surveillance System (NUHDSS), we examined the seasonal pattern of pneumonia mortality among under-five children living in Nairobi's slums. We included 17,787 under-five children resident in the NUHDSS from January 1, 2003 to December 31, 2005 in the analysis. Four hundred thirty-six deaths were observed and cause of death was ascertained by verbal autopsy for 377 of these deaths. Using Poisson regression, we modeled the quarterly mortality risk for pneumonia. The overall person-years (PYs) were 21,804 giving a mortality rate of 20.1 per 1,000 PYs in the study population. Pneumonia was the leading cause of death contributing 25.7% of the total deaths. Pneumonia mortality was highest in the second quarter (risk ratio [RR] = 2.3, confidence interval [CI]: 1.2-4.2 compared with the fourth quarter). The study provides evidence that pneumonia-related mortality among under-fives in Nairobi's slums is higher from April to June corresponding to the rainy season and the beginning of the cold season.


Highly Efficient CRISPR/Cas9-Mediated Cloning and Functional Characterization of Gastric Cancer-Derived Epstein-Barr Virus Strains.
The Epstein-Barr virus (EBV) is etiologically linked to approximately 10% of gastric cancers, in which viral genomes are maintained as multicopy episomes. EBV-positive gastric cancer cells are incompetent for progeny virus production, making viral DNA cloning extremely difficult. Here we describe a highly efficient strategy for obtaining bacterial artificial chromosome (BAC) clones of EBV episomes by utilizing a CRISPR/Cas9-mediated strand break of the viral genome and subsequent homology-directed repair. EBV strains maintained in two gastric cancer cell lines (SNU719 and YCCEL1) were cloned, and their complete viral genome sequences were determined. Infectious viruses of gastric cancer cell-derived EBVs were reconstituted, and the viruses established stable latent infections in immortalized keratinocytes. While Ras oncoprotein overexpression caused massive vacuolar degeneration and cell death in control keratinocytes, EBV-infected keratinocytes survived in the presence of Ras expression. These results implicate EBV infection in predisposing epithelial cells to malignant transformation by inducing resistance to oncogene-induced cell death. Recent progress in DNA-sequencing technology has accelerated EBV whole-genome sequencing, and the repertoire of sequenced EBV genomes is increasing progressively. Accordingly, the presence of EBV variant strains that may be relevant to EBV-associated diseases has begun to attract interest. Clearly, the determination of additional disease-associated viral genome sequences will facilitate the identification of any disease-specific EBV variants. We found that CRISPR/Cas9-mediated cleavage of EBV episomal DNA enabled the cloning of disease-associated viral strains with unprecedented efficiency. As a proof of concept, two gastric cancer cell-derived EBV strains were cloned, and the infection of epithelial cells with reconstituted viruses provided important clues about the mechanism of EBV-mediated epithelial carcinogenesis. This experimental system should contribute to establishing the relationship between viral genome variation and EBV-associated diseases.


Tyrosine aminotransferase: enzyme induction independent of adenosine 3', 5'-monophosphate.
The importance of adenyl cyclase and adenosine 3',5'-monophosphate in the induction of tyrosine aminotransferase by adrenocorticosteroids has been tested in HTC cells derived from a rat hepatoma and grown in tissue culture. Adrenocorticosteroids cause a 10-to 15-fold increase in the rate of synthesis of tyrosine aminotransferase in these cells. Under various experimental conditions, with or without glucocorticoids, neither adenyl cyclase nor cyclic adenosine mono-phosphate could be detected in HTC cells. In addition, neither the cyclic nucleotide nor N(6), O(2')-dibutyryl cyclic adenosine monophosphate caused increased activity of the transaminase in HTC cells. We conclude that induction of tyrosine aminotransferase by glucocorticoids is not mediated by the adenyl cyclase-cyclic adenosine monophosphate system.


Regression modeling of combined data from multiple sample surveys.
Combined data from multiple sample surveys are often used in population-based epidemiologic studies. Combining data can be beneficial in that sampling errors are reduced and coverage biases are corrected. Also, it is often necessary in order to use information lacking in one survey but available in another. We propose an estimation equations method for generalized linear models from the combined data. The estimation procedures for logistic regression models and Poisson regression models are developed. An example of estimating the relative risk of death by smoking status is used as an illustration and a simulation study is performed to examine the performance of the method.


Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.
Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs). The aim of this systematic review based on individual patient data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May 2011) and EMBASE (1974 to May 2011) to identify suitable trials. We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm or usual care/guidelines. Trials were excluded if they exclusively focused on paediatric patients or if they used procalcitonin for another purpose than to guide initiation and duration of antibiotic treatment. Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days. For the primary care setting, treatment failure was defined as death, hospitalisation, ARI-specific complications, recurrent or worsening infection, and patients reporting any symptoms of an ongoing respiratory infection at follow-up. For the ED setting, treatment failure was defined as death, ICU admission, re-hospitalisation after index hospital discharge, ARI-associated complications, and recurrent or worsening infection within 30 days of follow-up. For the ICU setting, treatment failure was defined as death within 30 days of follow-up. Secondary endpoints were antibiotic use (initiation of antibiotics, duration of antibiotics and total exposure to antibiotics (total amount of antibiotic days divided by total number of patients)), length of hospital stay for hospitalised patients, length of ICU stay for critically ill patients, and number of days with restricted activities within 14 days after randomisation for primary care patients.For the two co-primary endpoints of all-cause mortality and treatment failure, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression. The hierarchical regression model was adjusted for age and clinical diagnosis as fixed-effect. The different trials were added as random-effects into the model. We fitted corresponding linear regression models for antibiotic use. We conducted sensitivity analyses stratified by clinical setting and ARI diagnosis to assess the consistency of our results. We included 14 trials with 4221 participants. There were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting, or ARI diagnosis. These results proved robust in various sensitivity analyses. Total antibiotic exposure was significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4 (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and across all the different clinical settings and diagnoses. Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARI was not associated with higher mortality rates or treatment failure. Antibiotic consumption was significantly reduced across different clinical settings and ARI diagnoses. Further high-quality research is needed to confirm the safety of this approach for non-European countries and patients in intensive care. Moreover, future studies should also establish cost-effectiveness by considering country-specific costs of procalcitonin measurement and potential savings in consumption of antibiotics and other healthcare resources, as well as secondary cost savings due to lower risk of side effects and reduced antimicrobial resistance.


Schistosoma mansoni Infection as a Predictor of Low Aerobic Capacity in Ugandan Children.
Using the 20-meter shuttle run test (20mSRT) as a morbidity metric, we assessed whether Schistosoma mansoni infection was associated with decreased aerobic capacity in Ugandan children across a range of altitudes, either at low (∼600 m) or high (∼1,000 m) altitudes. A total of 305 children were recruited from six schools within the Buliisa District, Lake Albert, Uganda. A subset (n = 96) of these had been previously assessed and treated for schistosomiasis ± malaria 2 weeks prior. Fitness scores on the 20mSRT were translated into VO2max using a standardized equation. Unadjusted and multivariable-adjusted analyses were performed using VO2max as the primary outcome. Analysis of fitness scores from 304 children, inclusive of the subset follow-up cohort, revealed a median VO2max of 45.4 mL kg-1 min-1 (interquartile range: 42.9-48.0 mL kg-1 min-1). Children residing at high altitudes demonstrated increased aerobic capacities (46.3 versus 44.8 mL kg-1 min-1, P = 0.031). The prevalence of stunting, wasting, S. mansoni egg patent infection, malaria, giardiasis, anemia, and fecal occult blood were 36.7%, 16.1%, 44.3%, 65.2%, 21.4%, 50.6%, and 41.2%, respectively. Median VO2max was elevated in those previously treated, compared with those newly recruited (46.3 versus 44 mL kg-1 min-1, P < 0.001). Multivariable-adjusted analysis revealed a strong negative association between S. mansoni egg patent infection and VO2max at low altitude (beta coefficient: -3.96, 95% CI: -6.56 to -137, P = 0.004). This is the first study to document a negative association between S. mansoni infection and aerobic capacity at low altitudes using the 20mSRT.


Quantitative visualization of large variation phase objects.
This paper describes a technique by which a large variation phase object may be visualized in an image having an irradiance which is directly proportional to the object phase. An image of the phase object derivative is formed in a coherent optical system and recorded on photographic film. This photograph is used as the input to a second coherent optical system, in which the image is an integral of the input. No limitations are imposed on the maximum object phase, only on its maximum slope. Experimental techniques for implementation of this system are discussed and results shown.


Characterization of a variable angle reflection Fourier transform infrared accessory modified for surface plasmon resonance spectroscopy.
The Harrick AutoSeagull variable angle reflection accessory for Fourier transform infrared (FT-IR) spectrometers provides access to various spectroscopic techniques in a highly flexible platform. In particular, its ability to perform total internal reflection measurements is of interest because it also forms the basis for surface plasmon resonance (SPR) spectroscopy in prism-based configurations. The work presented here discusses the modification of the AutoSeagull to perform SPR spectroscopy, allowing for easy incorporation of the technique into most common FT-IR spectrometers. The wavelength dependency of the dielectric constant of the plasmon-supporting metal (in our case, gold) is largely responsible for the sensitivity attributed to changes in the sample's refractive index (RI) monitored by SPR spectroscopy. Furthermore, the optical properties of gold are such that when near-infrared (NIR) and/or mid-infrared (mid-IR) wavelengths are used to excite surface plasmons, higher sensitivities to RI changes are experienced compared to surface plasmons excited with visible wavelengths. The result is that in addition to instrumental simplicity, SPR analysis on FT-IR spectrometers, as permitted by the modified AutoSeagull, also benefits from the wavelength ranges accessible. Adaptation of the AutoSeagull to SPR spectroscopy involved the incorporation of slit apertures to minimize the angular spread reaching the detector, resulting in sharper SPR "dips" but at the cost of noisier spectra. In addition, discussion of the system's analytical performance includes comparison of dip quality as a function of slit size, tailoring of the dip minima location with respect to incident angle, and sensitivity to bulk RI changes.


Morphological response of songbirds to 100 years of landscape change in North America.
Major landscape changes caused by humans may create strong selection pressures and induce rapid evolution in natural populations. In the last 100 years, eastern North America has experienced extensive clear-cutting in boreal areas, while afforestation has occurred in most temperate areas. Based on museum specimens, I show that wings of several boreal forest songbirds and temperate songbirds of non-forest habitats have become more pointed over the last 100 years. In contrast, wings of most temperate forest and early-successional boreal forests species have become less pointed over the same period. In contrast to wing shape, the bill length of most species did not change significantly through time. These results are consistent with the "habitat isolation hypothesis", i.e., songbirds evolved in response to recent changes in the amount of available habitat and associated implications for mobility. Rapid morphological evolution may mitigate, without necessarily preventing, negative consequences of habitat loss caused by humans through direct exploitation or climate change.


Cigarette smoke selectively enhances viral PAMP- and virus-induced pulmonary innate immune and remodeling responses in mice.
Viral infections have more severe consequences in patients who have been exposed to cigarette smoke (CS) than in those not exposed to CS. For example, in chronic obstructive pulmonary disease (COPD), viruses cause more severe disease exacerbation, heightened inflammation, and accelerated loss of lung function compared with other causes of disease exacerbation. Symptomatology and mortality in influenza-infected smokers is also enhanced. To test the hypothesis that these outcomes are caused by CS-induced alterations in innate immunity, we defined the effects of CS on pathogen-associated molecular pattern-induced (PAMP-induced) pulmonary inflammation and remodeling in mice. CS was found to enhance parenchymal and airway inflammation and apoptosis induced by the viral PAMP poly(I:C). CS and poly(I:C) also induced accelerated emphysema and airway fibrosis. The effects of a combination of CS and poly(I:C) were associated with early induction of type I IFN and IL-18, later induction of IL-12/IL-23 p40 and IFN-gamma, and the activation of double-stranded RNA-dependent protein kinase (PKR) and eukaryotic initiation factor-2alpha (eIF2alpha). Further analysis using mice lacking specific proteins indicated a role for TLR3-dependent and -independent pathways as well as a pathway or pathways that are dependent on mitochondrial antiviral signaling protein (MAVS), IL-18Ralpha, IFN-gamma, and PKR. Importantly, CS enhanced the effects of influenza but not other agonists of innate immunity in a similar fashion. These studies demonstrate that CS selectively augments the airway and alveolar inflammatory and remodeling responses induced in the murine lung by viral PAMPs and viruses.


The personal value of being part of a Tropical Health Education Trust (THET) links programme to develop a palliative care degree programme in Sub Saharan Africa: a descriptive study of the views of volunteer UK health care professionals.
There is a global need to expand palliative care services to reach the increasing number requiring end of life care. In developing countries where the incidences of cancer are rising there is an urgent need to develop the palliative care workforce. This paper reports on a UK Department for international development (DFID) initiative funded through the Tropical Health Education Trust (THET) where palliative care staff, both clinical and academic, volunteered to help to develop, support and deliver a degree in palliative care in sub-Saharan Africa. The objective of the study was to explore the personal impact on the health care professionals of being part of this initiative. An evaluation approach using a confidential electronic survey containing quantitative and qualitative questions was distributed to all 17 volunteers on the programme, three months after completion of the first cohort. Data were analysed using descriptive statistics and content thematic analysis. Ethical review deemed the study to be service evaluation. 82 % (14) responded and several themes emerged from the data including the positive impact on teaching and educational skills; clinical practice and finally personal development. Using a score of 1-10 (1-no impact, 10 maximum impact) 'Lifestyle choices - life work balance' (rating 7.83) had the most impact. This approach to supporting the development of palliative care in Sub-Saharan Africa through skill sharing in supporting the delivery of a degree programme in palliative care was successful in terms of delivery of the degree programme, material development and mentorship of local staff. Additionally, this study shows it provided a range of positive impacts on the volunteer health care professionals from the UK. Professional impacts including increased management skills, and being better prepared to undertake a senior role. However it is the personal impact including lifestyle choices which the volunteers reported as the highest impact. Interestingly, several of the faculty have joined other volunteer programmes to continue to support the international development of palliative care.


Coordination of Atomic Co-Pt Coupling Species at Carbon Defects as Active Sites for Oxygen Reduction Reaction.
Platinum (Pt) is the state-of-the-art catalyst for oxygen reduction reaction (ORR), but its high cost and scarcity limit its large-scale use. However, if the usage of Pt reduces to a sufficiently low level, this critical barrier may be overcome. Atomically dispersed metal catalysts with high activity and high atom efficiency have the possibility to achieve this goal. Herein, we report a locally distributed atomic Pt-Co nitrogen-carbon-based catalyst (denoted as A-CoPt-NC) with high activity and robust durability for ORR (267 times higher than commercial Pt/C in mass activity). The A-CoPt-NC shows a high selectivity for the 4e- pathway in ORR, differing from the reported 2e- pathway characteristic of atomic Pt catalysts. Density functional theory calculations suggest that this high activity originates from the synergistic effect of atomic Pt-Co located on a defected C/N graphene surface. The mechanism is thought to arise from asymmetry in the electron distribution around the Pt/Co metal centers, as well as the metal atoms' coordination with local environments on the carbon surface. This coordination results from N8V4 vacancies (where N8 represents the number of nitrogen atoms and V4 indicates the number of vacant carbon atoms) within the carbon shell, which enhances the oxygen reduction reaction via the so-called synergistic effect.


[Children with attention deficit/hyperactivity disorder and pervasive developmental disorder:attention and response inhibition in the kiddie continuous performance test].
Continuous Performance Test (CPT) is widely used to assess the attention function and response inhibition in both children and adults. This study attempts to examine the performances of boys with attention deficit/hyperactivity disorder (AD/HD) and pervasive developmental disorder (PDD) with and without comorbid AD/HD using a CPT. Among the various versions of the CPT available, we used the Kiddie CPT (K-CPT) modified for younger children. The K-CPT was administered to children with AD/HD (n=22), those with PDD (n=19), and typically developing children (n=41) from 7 to 12 years of age. All children were drug free at the time of examination. The performances were examined in 6 measures:total number of omission errors (OE), total number of commission errors (CE), mean hit reaction time (HRT), hit reaction time standard error (HRTSE), perceptual sensitivity (d'), and response style (beta). Significantly lower scores in d' and a tendency to more errors in CE were found in the AD/HD group compared with the control group. Significantly lower scores in d' and significantly more errors in CE were also found in the PDD group with AD/HD symptoms compared with the control group. Moreover the AD/HD group showed significantly more errors in OE and higher scores in HRTSE compared with the control group. There were no significant group differences between the PDD group without AD/HD symptoms and the control group on all measures. Less favorable scores in AD/HD suggest inadequate selective attention, sustained attention and/or response inhibition. Results of the PDD group with comorbid AD/HD may reflect a basis of AD/HD impairment. Our findings may provide an understanding of neuropsychological characteristics underlying developmental disorders.


Characterization of Oil Palm Acyl-CoA-Binding Proteins and Correlation of Their Gene Expression with Oil Synthesis.
Acyl-CoA-binding proteins (ACBPs) are involved in binding and trafficking acyl-CoA esters in eukaryotic cells. ACBPs contain a well-conserved acyl-CoA-binding domain. Their various functions have been characterized in the model plant Arabidopsis and, to a lesser extent, in rice. In this study, genome-wide detection and expression analysis of ACBPs were performed on Elaeis guineensis (oil palm), the most important oil crop in the world. Seven E. guineensis ACBPs were identified and classified into four groups according to their deduced amino acid domain organization. Phylogenetic analysis showed conservation of this family with other higher plants. All seven EgACBPs were expressed in most tissues while their differential expression suggests various functions in specific tissues. For example, EgACBP3 had high expression in inflorescences and stalks while EgACBP1 showed strong expression in leaves. Because of the importance of E. guineensis as an oil crop, expression of EgACBPs was specifically examined during fruit development. EgACBP3 showed high expression throughout mesocarp development, while EgACBP1 had enhanced expression during rapid oil synthesis. In endosperm, both EgACBP1 and EgACBP3 exhibited increased expression during seed development. These results provide important information for further investigations on the biological functions of EgACBPs in various tissues and, in particular, their roles in oil synthesis.


Economic burden of high-responding inhibitors in patients with hemophilia A in Taiwan.
Hemophilia A (HA) is the most common X-linked inherited bleeding disorder. In some patients with HA, particularly those with severe HA, replacement therapy results in the production of high-responding clotting factor VIII inhibitors. The economic burden of this complication is the highest reported for a chronic disease. Our aim was to investigate the direct medical expenditure burden of high-responding inhibitors in patients with HA. A retrospective study was conducted using the National Health Insurance Research Database, utilizing data covering the period of 2004-2007. In total, 638 males with HA¸ including 37 patients with high-responding inhibitors were evaluated. Over 99% of the annual median medical expenditure was attributable to the cost of clotting factor concentrates (CFCs) in patients with high-responding inhibitors. The annual median expenditure related to CFCs of the total medical care and outpatient care were US$170611 and US$141982, respectively, and were 4.6- and 4.3-fold higher in these patients during the study period, respectively. In patients with high-responding inhibitors, the median hospitalization expenditure and daily hospitalization cost with or without surgical procedures were 3.0- and 2.4-fold higher, respectively, and 4.3 and 5.6-fold higher, respectively. Our data reveal higher medical expenditures burden for patients with HA and high-responding inhibitors in Taiwan. Future research is encouraged to evaluate the impact of this burden on patient quality of life.


Small things make a big difference: binder effects on the performance of Li and Na batteries.
Li and Na batteries are very important as energy storage devices for electric vehicles and smart grids. It is well known that, when an electrode is analysed in detail, each of the components (the active material, the conductive carbon, the current collector and the binder) makes a portion of contribution to the battery performance in terms of specific capacity, rate capability, cycle life, etc. However, there has not yet been a review on the binder, though there are already many review papers on the active materials. Binders make up only a small part of the electrode composition, but in some cases, they play an important role in affecting the cycling stability and rate capability for Li-ion and Na-ion batteries. Poly(vinylidene difluoride) (PVDF) has been the mainstream binder, but there have been discoveries that aqueous binders can sometimes make a battery perform better, not to mention they are cheaper, greener, and easier to use for electrode fabrication. In this review, we focus on several kinds of promising electrode materials, to show how their battery performance can be affected significantly by binder materials: anode materials such as Si, Sn and transitional metal oxides; cathode materials such as LiFePO4, LiNi1/3Co1/3Mn1/3O2, LiCoO2 and sulphur.