Biliary excretion and enterohepatic cycling of zearalenone in immature pigs.
The disposition of the estrogenic mycotoxin, zearalenone (ZEN) in female, 10- to 14-week-old Yorkshire pigs was investigated. Pigs were administered [3H]ZEN intravenously (IV; n = 4; 5 mg/kg; 15 microCi/kg), orally (n = 4; 10 mg/kg; 30 microCi/kg), or intravenously with bile removal (IVB; n = 2; 5 mg/kg; 15 microCi/kg). Plasma, urine, feces, and bile (IVB pigs only) were serially collected and analyzed for radioactivity. Metabolite profiles were determined in plasma and bile by HPLC. The biological half-life of total plasma radioactivity in IV and orally dosed pigs (86.6 hr) was much larger than that of IVB animals (3.34 hr). Metabolite profiles of plasma concentration vs time demonstrated secondary peaks in concentration during the terminal elimination phase in IV and orally dosed pigs. In IVB pigs these peaks were absent, relative metabolite profiles were altered, and ZEN and metabolites were no longer detectable after 16 hr post-dosing. Biliary recovery of radioactivity, principally as glucuronide conjugates, was extensive (45.61 +/- 4.7%) in IVB pigs and significantly greater (p < 0.05) than that of fecal recovery of radioactivity in IV (6.56 +/- 0.78) or orally dosed (21.74 +/- 1.56%) pigs. Intraduodenal administration of bile containing [3H]ZEN and metabolites resulted in recovery of 64.56 +/- 4.89% of the dose in bile, 20.78 +/- 3.94% in urine, and the presence of glucuronide conjugates of ZEN and alpha-zearalenol (ZEL) in portal and jugular plasma. Differences in metabolite profiles between administered bile and sampled plasma suggest that the intestinal mucosa was active in reducing ZEN to ZEL and conjugating these metabolites with glucuronic acid. These studies provide evidence for extensive biliary secretion and enterohepatic cycling of ZEN and metabolites in pigs.


Measuring the Implementation of Youth Empowerment Solutions.
Scholars have increasingly emphasized the importance of using evidence-based programs to promote health and prevent disease. While theoretically and empirically based programs may be effective in carefully controlled conditions, many fail to achieve desired outcomes when implemented in real-world settings. Ensuring high-quality implementation of health promotion programs is critically important as variation in implementation is closely associated with program effectiveness. The purpose of this article is to present methods used to document and assess the implementation of the Youth Empowerment Solutions (YES) program. We collected process evaluation data on 25 YES groups from 12 schools over a period of 4 years. The evaluation assessed four key aspects of delivery: fidelity, dose delivered, dose received, and program quality. We found wide variations in delivery for some measures, while others were more consistent across groups. These indicators of program delivery provided a strong basis for evaluating program implementation, taking actions to improve it, and ultimately, deepening understanding of program effectiveness. The study suggests a model for using multiple methods to collect and analyze data about aspects of program delivery to guide future implementations.


Dislocation reactions, grain boundaries, and irreversibility in two-dimensional lattices using topological tweezers.
Dislocations, disclinations, and grain boundaries are topological excitations of crystals that play a key role in determining out-of-equilibrium material properties. In this article we study the kinetics, creation, and annihilation processes of these defects in a controllable way by applying "topological tweezers," an array of weak optical tweezers which strain the lattice by weakly pulling on a collection of particles without grabbing them individually. We use topological tweezers to deterministically control individual dislocations and grain boundaries, and reversibly create and destroy dislocation pairs in a 2D crystal of charged colloids. Starting from a perfect lattice, we exert a torque on a finite region and follow the complete step-by-step creation of a disoriented grain, from the creation of dislocation pairs through their reactions to form a grain boundary and their reduction of elastic energy. However, when the grain is rotated back to its original orientation the dislocation reactions do not retrace. Rather, the process is irreversible; the grain boundary expands instead of collapsing.


Human DNA polymerase eta activity and translocation is regulated by phosphorylation.
Human DNA polymerase eta (pol eta) can replicate across UV-induced pyrimidine dimers, and defects in the gene encoding pol eta result in a syndrome called xeroderma pigmentosum variant (XP-V). XP-V patients are prone to the development of cancer in sun-exposed areas, and cells derived from XP-V patients demonstrate increased sensitivity to UV radiation and a higher mutation rate compared with wild-type cells. pol eta has been shown to replicate across a wide spectrum of DNA lesions introduced by environmental or chemotherapeutic agents, or during nucleotide starvation, suggesting that the biological roles for pol eta are not limited to repair of UV-damaged DNA. The high error rate of pol eta requires that its intracellular activity be tightly regulated. Here, we show that the phosphorylation of pol eta increased after UV irradiation, and that treatment with caffeine, siRNA against ATR, or an inhibitor of PKC (calphostin C), reduced the accumulation of pol eta at stalled replication forks after UV irradiation or treatment with cisplatin and gemcitabine. Site-specific mutagenesis (S587A and T617A) of pol eta at two putative PKC phosphorylation sites located in the protein-protein interaction domain prevented nuclear foci formation induced by UV irradiation or treatment with gemcitabine/cisplatin. In addition, XP-V cell lines stably expressing either the S587A or T617A mutant form of pol eta were more sensitive to UV radiation and gemcitabine/cisplatin than control cells expressing wild-type pol eta. These results suggest that phosphorylation is one mechanism by which the cellular activity of pol eta is regulated.


Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.
Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo.


Lysophosphatidic Acid Induces Ligamentum Flavum Hypertrophy Through the LPAR1/Akt Pathway.
Hypertrophic ligamentum flavum (LF) is a major cause of lumbar spinal stenosis. Our previous work showed that high levels of lysophosphatidic acid (LPA) expression are positively correlated with LF hypertrophy. This study aimed to further unveil how LPA regulates LF hypertrophy Methods: We studied LPAR1 expression in human LF cells using PCR and western blotting. Cell viability cell cycle, apoptosis rate and molecular mechanisms were assayed in LPAR1 knockdown or overexpression LF cells. LF hypertrophy and the molecular mechanism was confirmed in human samples and in in vivo studies. The expression of LPA and its receptor LPAR1 is significantly higher in tissues or cells harvested from hypertrophic LF compared to healthy controls. Moreover, LPA promoted LF cell proliferation by interacting with LPAR1. This conclusion is supported by the fact that depletion or overexpression of LPAR1 changed the effect of LPA on LF cell proliferation. LPA also inhibits apoptosis in LF cells through the receptor LPAR1. Importantly, we demonstrated that the LPA-LPAR1 interaction initiated Akt phosphorylation and determined cell proliferation and apoptosis. Our in vitro findings were supported by our in vivo evidence that lyophilized LPA significantly induced LF hypertrophy via the LPAR1-Akt signaling pathway. More importantly, targeted inhibition of LPAR1 by Ki16425 with a gel sponge implant effectively reduced LPA-associated LF hypertrophy. Taken together, these data indicate that LPA binds to the receptor LPAR1 to induce LF cell proliferation and inhibit apoptosis by activating AKT signaling cascades. Targeting this signaling cascade with Ki16425 is a potential therapeutic strategy for preventing LF hypertrophy. LPA-LPAR1-Akt activation is positively correlated with the proliferation and survival of LF cells. LPAR1 could be a target for new drugs and the development of new therapeutic methods for treating LF hypertrophy.


Effect of scaffold architecture and BMP-2/BMP-7 delivery on in vitro bone regeneration.
The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(ε-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not have a significant effect on the kinetics of release of the model protein BSA; but affected proliferation of bone marrow mesenchymal stem cells. Cell proliferation on random scaffolds was significantly higher compared to the oriented ones. Delivery of BMP-2 alone suppressed MSC proliferation and increased the ALP activity to a higher level than that with BMP-7 delivery. Proliferation rate was suppressed the most by the sequential delivery of the two growth factors from the random scaffold on which the ALP activity was the highest. Results indicated the distinct effect of scaffold architecture and the mode of growth factor delivery on the proliferation and osteogenic differentiation of MSCs, enabling us to design multifunctional scaffolds capable of controlling bone healing.


The Associations of Gender With Social Participation of Burn Survivors: A Life Impact Burn Recovery Evaluation Profile Study.
Burn injury can be debilitating and affect survivors' quality of life in a profound fashion. Burn injury may also lead to serious psychosocial challenges that have not been adequately studied and addressed. Specifically, there has been limited research into the associations of burn injury on community reintegration based on gender. This work analyzed data from 601 burn survivors who completed field testing of a new measure of social participation for burn survivors, the Life Impact Burn Recovery Evaluation (LIBRE) Profile. Differences in item responses between men and women were examined. Scores on the six LIBRE Profile scales were then compared between men and women using analysis of variance and adjusted linear multivariate regression modeling. Overall, men scored significantly better than women on four of the six LIBRE Profile scales: Sexual Relationships, Social Interactions, Work & Employment, and Romantic Relationships. Differences were not substantially reduced after adjustment for demographic characteristics and burn size. Men scored better than women in most of the areas measured by the LIBRE Profile. These gender differences are potentially important for managing burn patients during the post-injury recovery period.


Stratification of Archaea in the deep sediments of a freshwater meromictic lake: vertical shift from methanogenic to uncultured archaeal lineages.
As for lineages of known methanogens, several lineages of uncultured archaea were recurrently retrieved in freshwater sediments. However, knowledge is missing about how these lineages might be affected and structured according to depth. In the present study, the vertical changes of archaeal communities were characterized in the deep sediment of the freshwater meromictic Lake Pavin. For that purpose, an integrated molecular approach was performed to gain information on the structure, composition, abundance and vertical stratification of archaeal communities thriving in anoxic freshwater sediments along a gradient of sediments encompassing 130 years of sedimentation. Huge changes occurred in the structure and composition of archaeal assemblages along the sediment core. Methanogenic taxa (i.e. Methanosaeta and Methanomicrobiales) were progressively replaced by uncultured archaeal lineages (i.e. Marine Benthic Group-D (MBG-D) and Miscellaneous Crenarchaeal Group (MCG)) which are suspected to be involved in the methane cycle.


Artificial and bioartificial liver devices: present and future.
Liver failure is associated with high morbidity and mortality without transplantation. There are two types of device for temporary support: artificial and bioartificial livers. Artificial livers essentially use non-living components to remove the toxins accumulated during liver failure. Bioartificial livers have bioreactors containing hepatocytes to provide both biotransformation and synthetic liver functions. We review here the operating principles, chemical effects, clinical effects and complications of both types, with specific attention paid to bioartificial systems. Several artificial support systems have FDA marketing authorisation or are CE labelled, but the improvement they provide in terms of patient clinical outcome has not yet been fully demonstrated. At present, different bioartifical systems are being investigated clinically on the basis of their promises and capacity to provide and replace most liver functions. However, important issues such as cost, cell availability, maintenance of cell viability and functionality throughout treatment, and regulatory issues, as well as difficult challenges, including implementing cell-housing devices at the patient's bedside on an emergency basis, have delayed their appearance in intensive care units and on the market. Bioreactors are, nevertheless, when combined with artificial components, a pragmatic approach for future treatment of liver failure.


Sperm storage induces an immunity cost in ants.
Ant queens are among the most long-lived insects known. They mate early in adult life and maintain millions of viable sperm in their sperm storage organ until they die many years later. Because they never re-mate, the reproductive success of queens is ultimately sperm-limited, but it is not known what selective forces determine the upper limit to sperm storage. Here we show that sperm storage carries a significant cost of reduced immunity during colony founding. Newly mated queens of the leaf-cutting ant Atta colombica upregulate their immune response shortly after completing their nest burrow, probably as an adaptive response to a greater exposure to pathogens in the absence of grooming workers. However, the immune response nine days after colony founding is negatively correlated with the amount of sperm in the sperm storage organ, indicating that short-term survival is traded off against long-term reproductive success. The immune response was lower when more males contributed to the stored sperm, indicating that there might be an additional cost of mating or storing genetically different ejaculates.


Structural insights into the mechanism of the membrane integral N-acyltransferase step in bacterial lipoprotein synthesis.
Lipoproteins serve essential roles in the bacterial cell envelope. The posttranslational modification pathway leading to lipoprotein synthesis involves three enzymes. All are potential targets for the development of new antibiotics. Here we report the crystal structure of the last enzyme in the pathway, apolipoprotein N-acyltransferase, Lnt, responsible for adding a third acyl chain to the lipoprotein's invariant diacylated N-terminal cysteine. Structures of Lnt from Pseudomonas aeruginosa and Escherichia coli have been solved; they are remarkably similar. Both consist of a membrane domain on which sits a globular periplasmic domain. The active site resides above the membrane interface where the domains meet facing into the periplasm. The structures are consistent with the proposed ping-pong reaction mechanism and suggest plausible routes by which substrates and products enter and leave the active site. While Lnt may present challenges for antibiotic development, the structures described should facilitate design of therapeutics with reduced off-target effects.


Survival after liver transplantation in the United Kingdom and Ireland compared with the United States.
Surgical mortality in the US is widely perceived to be superior to that in the UK. However, previous comparisons of surgical outcome in the two countries have often failed to take sufficient account of case-mix or examine long-term outcome. The standardised nature of liver transplantation practice makes it uniquely placed for undertaking reliable international comparisons of surgical outcome. The objective of this study is to undertake a risk-adjusted disease-specific comparison of both short- and long-term survival of liver transplant recipients in the UK and Ireland with that in the US. A multicentre cohort study using two high quality national databases including all adults who underwent a first single organ liver transplant in the UK and Ireland (n = 5925) and the US (n = 41,866) between March 1994 and March 2005. The main outcome measures were post-transplant mortality during the first 90 days, 90 days to 1 year and beyond the first year, adjusted for recipient and donor characteristics. Risk-adjusted mortality in the UK and Ireland was generally higher than in the US during the first 90 days (HR 1.17; 95% CI 1.07 to 1.29), both for patients transplanted for acute liver failure (HR 1.27; 95% CI 1.01 to 1.60) and those transplanted for chronic liver disease (HR 1.18; 95% CI 1.07 to 1.31). Between 90 days and 1 year post-transplantation, no statistically significant differences in overall risk-adjusted mortality were noted between the two cohorts. Survivors of the first post-transplant year in the UK and Ireland had lower overall risk-adjusted mortality than those transplanted in the US (HR 0.88; 95% CI 0.81 to 0.96). This difference was observed among patients transplanted for chronic liver disease (HR 0.88; 95% CI 0.81 to 0.96), but not those transplanted for acute liver failure (HR 1.02; 95% CI 0.70 to 1.50). Whilst risk-adjusted mortality is higher in the UK and Ireland during the first 90 days following liver transplantation, it is higher in the US among those liver transplant recipients who survived the first post-transplant year. Our results are consistent with the notion that the US has superior acute perioperative care whereas the UK appears to provide better quality chronic care following liver transplantation surgery.


CAFASP2: the second critical assessment of fully automated structure prediction methods.
The results of the second Critical Assessment of Fully Automated Structure Prediction (CAFASP2) are presented. The goals of CAFASP are to (i) assess the performance of fully automatic web servers for structure prediction, by using the same blind prediction targets as those used at CASP4, (ii) inform the community of users about the capabilities of the servers, (iii) allow human groups participating in CASP to use and analyze the results of the servers while preparing their nonautomated predictions for CASP, and (iv) compare the performance of the automated servers to that of the human-expert groups of CASP. More than 30 servers from around the world participated in CAFASP2, covering all categories of structure prediction. The category with the largest participation was fold recognition, where 24 CAFASP servers filed predictions along with 103 other CASP human groups. The CAFASP evaluation indicated that it is difficult to establish an exact ranking of the servers because the number of prediction targets was relatively small and the differences among many servers were also small. However, roughly a group of five "best" fold recognition servers could be identified. The CASP evaluation identified the same group of top servers albeit with a slightly different relative order. Both evaluations ranked a semiautomated method named CAFASP-CONSENSUS, that filed predictions using the CAFASP results of the servers, above any of the individual servers. Although the predictions of the CAFASP servers were available to human CASP predictors before the CASP submission deadline, the CASP assessment identified only 11 human groups that performed better than the best server. Furthermore, about one fourth of the top 30 performing groups corresponded to automated servers. At least half of the top 11 groups corresponded to human groups that also had a server in CAFASP or to human groups that used the CAFASP results to prepare their predictions. In particular, the CAFASP-CONSENSUS group was ranked 7. This shows that the automated predictions of the servers can be very helpful to human predictors. We conclude that as servers continue to improve, they will become increasingly important in any prediction process, especially when dealing with genome-scale prediction tasks. We expect that in the near future, the performance difference between humans and machines will continue to narrow and that fully automated structure prediction will become an effective companion and complement to experimental structural genomics.


A multidisciplinary rehabilitation programme for cancer cachexia improves quality of life.
Patients with cancer cachexia have severely impaired quality of life (QoL). Multidisciplinary, multimodal treatment approaches have potential for stabilising weight and correcting other features of this syndrome, but the impact on QoL is unknown. A retrospective analysis of QoL in patients with advanced cancer, referred for the management of cachexia by a specialised multidisciplinary clinic (The McGill Cancer Nutrition Rehabilitation Program clinic at the Jewish General Hospital (CNR-JGH)). QoL was assessed at visits 1-3 using a dedicated QoL tool for cachexia, and the change in QoL was calculated for each patient. The correlation between clinical features and QoL at baseline and subsequent change in QoL was analysed, to determine what factors predict improvements in QoL during the CNR-JGH intervention. 374 patients assessed at visit 1 with mean weight loss of 10.2% over the preceding 6 months. Baseline QoL scores were severely impaired but clinically important improvements were observed over visits 1-3 to the CNR-JGH clinic. Improvements in QoL were not determined by baseline characteristics and were similar in all patient subgroups. However, those patients who gained weight and increased their 6 min walk test (6MWT) had the greatest improvements in QoL. Improving management of all facets of the cancer cachexia syndrome, including poor QoL, remains a priority. The multimodal approach to management of cancer cachexia offered by the CNR-JGH results in clinically important improvements in QoL. All patients who are able to receive this type of intervention have similar potential to improve their QoL, but the greatest benefits are seen in those who gain weight and improve their 6MWT.


Assessing the Value of the Zebrafish Conditioned Place Preference Model for Predicting Human Abuse Potential.
Regulatory agencies recommend that centrally active drugs are tested for abuse potential before approval. Standard preclinical assessments are conducted in rats or non-human primates (NHPs). This study evaluated the ability of the zebrafish conditioned place preference (CPP) model to predict human abuse outcomes. Twenty-seven compounds from a variety of pharmacological classes were tested in zebrafish CPP, categorized as positive or negative, and analyzed using standard diagnostic tests of binary classification to determine the likelihood that zebrafish correctly predict robust positive signals in human subjective effects studies (+HSE) and/or Drug Enforcement Administration drug scheduling. Results were then compared with those generated for rat self-administration and CPP, as well as NHP self-administration, using this same set of compounds. The findings reveal that zebrafish concordance and sensitivity values were not significantly different from chance for both +HSE and scheduling. Although significant improvements in specificity and negative predictive values were observed for zebrafish relative to +HSE, specificity without sensitivity provides limited predictive value. Moreover, assessments in zebrafish provided no added value for predicting scheduling. By contrast, rat and NHP models generally possessed significantly improved concordance, sensitivity, and positive predictive values for both clinical measures. Although there may be predictive value with compounds from specific pharmacological classes (e.g., µ-opioid receptor agonists, psychostimulants) for zebrafish CPP, altogether these data highlight that using the current methodology, the zebrafish CPP model does not add value to the preclinical assessment of abuse potential.


Ethanol production by thermophilic bacteria: relationship between fermentation product yields of and catabolic enzyme activities in Clostridium thermocellum and Thermoanaerobium brockii.
Significant quantitative differences in end-product yields by two strains of Clostridium thermocellum and one strain of Thermoanaerobium brockii were observed during cellobiose fermentation. Most notably, the ethanol/H(2) and lactate/acetate ratios were drastically higher for T. brockii as compared with C. thermocellum strains LQRI and AS39. Exogenous H(2) addition (0.4 to 1.0 atm) during culture growth increased the ethanol/acetate ratio of both T. brockii and AS39 but had no effect on LQRI. All strains had an operative Embden-Meyerhof glycolytic pathway and displayed catabolic activities of fructose-1,6-diphosphate-activated lactate dehydrogenase, coenzyme A acetylating pyruvate and acetaldehyde dehydrogenase, hydrogenase, ethanol dehydrogenase, and acetate kinase. Enzyme kinetic properties (apparent K(m), V(max), and Q(10) values) and the specificity of electron donors/acceptors for different oxidoreductases involved in pyruvate conversion to fermentation products were compared in the three strains. Both species contained ferredoxin-linked pyruvate dehydrogenase and pyridine nucleotide oxidoreductases. Ferredoxin-nicotinamide adenine dinucleotide (NAD) reductase activity was significantly higher in T. brockii than in AS39 and was not detectable in LQRI. H(2) production and hydrogenase activity were inversely related to ferredoxin-NAD reductase activity in the three strains. Ferredoxin-NAD phosphate reductase activity was present in cell extracts of both species. Alcohol dehydrogenase activity in C. thermocellum was NAD dependent, unidirectional, and inhibited by low concentrations of NAD and ethanol. Ethanol dehydrogenase activity of T. brockii was both NAD and NADP linked, reversible, and not inhibited by low levels of reaction products. The high lactate yield of T. brockii correlated with increased fructose-1,6-diphosphate. The relation of catabolic enzyme activity and quantitative differences in intracellular electron flow and fermentation product yields of these thermophilic bacteria is discussed.


Formation of Triboelectric Series via Atomic-Level Surface Functionalization for Triboelectric Energy Harvesting.
Triboelectric charging involves frictional contact of two different materials, and their contact electrification usually relies on polarity difference in the triboelectric series. This limits the choices of materials for triboelectric contact pairs, hindering research and development of energy harvest devices utilizing triboelectric effect. A progressive approach to resolve this issue involves modification of chemical structures of materials for effectively engineering their triboelectric properties. Here, we describe a facile method to change triboelectric property of a polymeric surface via atomic-level chemical functionalizations using a series of halogens and amines, which allows a wide spectrum of triboelectric series over single material. Using this method, tunable triboelectric output power density is demonstrated in triboelectric generators. Furthermore, molecular-scale calculation using density functional theory unveils that electrons transferred through electrification are occupying the PET group rather than the surface functional group. The work introduced here would open the ability to tune triboelectric property of materials by chemical modification of surface and facilitate the development of energy harvesting devices and sensors exploiting triboelectric effect.


Consensus structures of the Mo(v) sites of sulfite-oxidizing enzymes derived from variable frequency pulsed EPR spectroscopy, isotopic labelling and DFT calculations.
Sulfite-oxidizing enzymes from eukaryotes and prokaryotes have five-coordinate distorted square-pyramidal coordination about the molybdenum atom. The paramagnetic Mo(v) state is easily generated, and over the years four distinct CW EPR spectra have been identified, depending upon enzyme source and the reaction conditions, namely high and low pH (hpH and lpH), phosphate inhibited (Pi) and sulfite (or blocked). Extensive studies of these paramagnetic forms of sulfite-oxidizing enzymes using variable frequency pulsed electron spin echo (ESE) spectroscopy, isotopic labeling and density functional theory (DFT) calculations have led to the consensus structures that are described here. Errors in some of the previously proposed structures are corrected.


Understanding the Effect of Particle Size and Processing on Almond Lipid Bioaccessibility through Microstructural Analysis: From Mastication to Faecal Collection.
We have previously reported on the low lipid bioaccessibility from almond seeds during digestion in the upper gastrointestinal tract (GIT). In the present study, we quantified the lipid released during artificial mastication from four almond meals: natural raw almonds (NA), roasted almonds (RA), roasted diced almonds (DA) and almond butter from roasted almonds (AB). Lipid release after mastication (8.9% from NA, 11.8% from RA, 12.4% from DA and 6.2% from AB) was used to validate our theoretical mathematical model of lipid bioaccessibility. The total lipid potentially available for digestion in AB was 94.0%, which included the freely available lipid resulting from the initial sample processing and the further small amount of lipid released from the intact almond particles during mastication. Particle size distributions measured after mastication in NA, RA and DA showed most of the particles had a size of 1000 µm and above, whereas AB bolus mainly contained small particles (<850 µm). Microstructural analysis of faecal samples from volunteers consuming NA, RA, DA and AB confirmed that some lipid in NA, RA and DA remained encapsulated within the plant tissue throughout digestion, whereas almost complete digestion was observed in the AB sample. We conclude that the structure and particle size of the almond meals are the main factors in regulating lipid bioaccessibility in the gut.


Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization.
Liquid-liquid phase separation (LLPS) mediates formation of membraneless condensates such as those associated with RNA processing, but the rules that dictate their assembly, substructure, and coexistence with other liquid-like compartments remain elusive. Here, we address the biophysical mechanism of this multiphase organization using quantitative reconstitution of cytoplasmic stress granules (SGs) with attached P-bodies in human cells. Protein-interaction networks can be viewed as interconnected complexes (nodes) of RNA-binding domains (RBDs), whose integrated RNA-binding capacity determines whether LLPS occurs upon RNA influx. Surprisingly, both RBD-RNA specificity and disordered segments of key proteins are non-essential, but modulate multiphase condensation. Instead, stoichiometry-dependent competition between protein networks for connecting nodes determines SG and P-body composition and miscibility, while competitive binding of unconnected proteins disengages networks and prevents LLPS. Inspired by patchy colloid theory, we propose a general framework by which competing networks give rise to compositionally specific and tunable condensates, while relative linkage between nodes underlies multiphase organization.


Family members' retrospective stories of the treatment stage of an adolescent or young adult who subsequently died of cancer.
Adolescents and young adults (AYAs) with cancer have been recognized as being disadvantaged within the present healthcare system. This article is part of a major study that was motivated by the principal researcher's own experience of her 17-year-old son dying of cancer and from current literature that highlights the lack of support and understanding of AYAs and their families. This article aimed to uncover from the stories of family members the experience after the treatment of an adolescent or young adult family member (aged 13-23 years) who subsequently died. Narrative inquiry was determined to be the appropriate methodology for this study. The participants were a self-selected purposeful sample of 26 family members whose narratives spoke of experience of having an AYA family member live with and die of cancer. The meta-narrative of the families' stories in the treatment stage resulted in 6 themes. This article provides the insights of experience of the family members within the treatment stage. The family members speak of a health system unable to respond to the AYA and family member's needs and the suffering sacrifice and courage of the AYAs and the family members. There is evidence that AYAs and family members are lost in the system, with minimum understanding or support for this unique group of people. Further research is required to assist the development of evidence-based best practice models of care for AYAs and their families.


Infraorbital nerve: a surgically relevant landmark for the pterygopalatine fossa, cavernous sinus, and anterolateral skull base in endoscopic transmaxillary approaches.
OBJECTIVE Endoscopic transmaxillary approaches (ETMAs) address pathology of the anterolateral skull base, including the cavernous sinus, pterygopalatine fossa, and infratemporal fossa. This anatomically complex region contains branches of the trigeminal nerve and external carotid artery and is in proximity to the internal carotid artery. The authors postulated, on the basis of intraoperative observations, that the infraorbital nerve (ION) is a useful surgical landmark for navigating this region; therefore, they studied the anatomy of the ION and its relationships to critical neurovascular structures and the maxillary nerve (V2) encountered in ETMAs. METHODS Endoscopic anatomical dissections were performed bilaterally in 5 silicone-injected, formalin-fixed cadaveric heads (10 sides). Endonasal transmaxillary and direct transmaxillary (Caldwell-Luc) approaches were performed, and anatomical correlations were analyzed and documented. Stereotactic imaging of each specimen was performed to correlate landmarks and enable precise measurement of each segment. RESULTS The ION was readily identified in the roof of the maxillary sinus at the beginning of the surgical procedure in all specimens. Anatomical dissections of the ION and the maxillary branch of the trigeminal nerve (V2) to the cavernous sinus suggested that the ION/V2 complex has 4 distinct segments that may have implications in endoscopic approaches: 1) Segment I, the cutaneous segment of the ION and its terminal branches (5-11 branches) to the face, distal to the infraorbital foramen; 2) Segment II, the orbitomaxillary segment of the ION within the infraorbital canal from the infraorbital foramen along the infraorbital groove (length 12 ± 3.2 mm); 3) Segment III, the pterygopalatine segment within the pterygopalatine fossa, which starts at the infraorbital groove to the foramen rotundum (13 ± 2.5 mm); and 4) Segment IV, the cavernous segment from the foramen rotundum to the trigeminal ganglion (15 ± 4.1 mm), which passes in the lateral wall of the cavernous sinus. The relationship of the ION/V2 complex to the contents of the cavernous sinus, carotid artery, and pterygopalatine fossa is described in the text. CONCLUSIONS The ION/V2 complex is an easily identifiable and potentially useful surgical landmark to the foramen rotundum, cavernous sinus, carotid artery, pterygopalatine fossa, and anterolateral skull base during ETMAs.


The Enthalpy-entropy Compensation Phenomenon. Limitations for the Use of Some Basic Thermodynamic Equations.
The thermodynamic analyses of proteins, protein-ligands and protein-nucleic acid complexes involves the entropy-enthalpy (S-H) compensation phenomenon. We have examined the question whether the observed compensation is artificial or reflects anything more than the well-known laws of statistical thermodynamics (so-called extra-thermodynamic compensation). We have shown that enthalpy- entropy compensation (EEC) is mainly the trivial consequence of the basic thermodynamic laws and there are no experimental evidences for existence of the extra-thermodynamic compensation. In most cases EEC obtained in the experiments through the plot enthalpies (ΔH) and entropies (TΔS) versus one another is meaningless due to the large correlated errors in ΔH and TΔS, unless special measures are taken to minimize, quantify and propagate these errors. Van't Hoff equation can be used for entropy calculation in limited cases when enthalpy is measured in independent experiments. Eyring equation cannot be used for calculation of entropy in any case and should be excluded from scientific use. Both equation, Van't Hoff and Eyring cannot be used for simultaneous calculation of the enthalpy and entropy values using one set of data. All the data obtained in this way should be recognized as erroneous.


The size of sites containing SR proteins in human nuclei. Problems associated with characterizing small structures by immunogold labeling.
Some SR proteins are associated with eukaryotic transcripts as they move from synthetic sites (transcription "factories"), through downstream sites, to nuclear pores. Downstream sites can also be isolated as large nuclear ribonucleoprotein particles of approximately 200 S (diameter approximately 50 nm). In ultrathin sections of HeLa nuclei, indirect immunogold labeling with a specific antibody gives many small clusters of approximately 10 gold particles (diameter 50-80 nm). We gauged errors in estimating the diameter of underlying structures marked by immunogold probes (lengths approximately 20 nm). We examined systematically how probe dimensions affected cluster diameter. Probes contained one to three immunoglobulin molecules, sometimes a protein A molecule, and a gold particle of 5-15 nm. We found that (a) immunolabeling particles were tightly packed, (b) reducing particle size by 5 nm reduced cluster diameter by 10 nm, (c) reducing the number of immunoglobulins in the immunolabeling sandwich from three to two reduced cluster diameter by approximately 4 nm, (d) replacing the last immunoglobulin in a sandwich with protein A increased diameter by approximately 7 nm and led to a peripheral concentration of particles, and (e) increasing the number of layers in the sandwich increased sensitivity. Assuming that underlying structures had diameters of 50 nm, we find that errors ranged from -20% to +50%.


A comparative analysis of methylome profiles of Campylobacter jejuni sheep abortion isolate and gastroenteric strains using PacBio data.
Campylobacter jejuni is a leading cause of human gastrointestinal disease and small ruminant abortions in the United States. The recent emergence of a highly virulent, tetracycline-resistant C. jejuni subsp. jejuni sheep abortion clone (clone SA) in the United States, and that strain's association with human disease, has resulted in a heightened awareness of the zoonotic potential of this organism. Pacific Biosciences' Single Molecule, Real-Time sequencing technology was used to explore the variation in the genome-wide methylation patterns of the abortifacient clone SA (IA3902) and phenotypically distinct gastrointestinal-specific C. jejuni strains (NCTC 11168 and 81-176). Several notable differences were discovered that distinguished the methylome of IA3902 from that of 11168 and 81-176: identification of motifs novel to IA3902, genome-specific hypo- and hypermethylated regions, strain level variability in genes methylated, and differences in the types of methylation motifs present in each strain. These observations suggest a possible role of methylation in the contrasting disease presentations of these three C. jejuni strains. In addition, the methylation profiles between IA3902 and a luxS mutant were explored to determine if variations in methylation patterns could be identified that might explain the role of LuxS-dependent methyl recycling in IA3902 abortifacient potential.


Use of voriconazole in a patient with aspergilloma caused by an itraconazole-resistant strain of Aspergillus fumigatus.
The case is reported of a patient with cavitary sarcoidosis complicated by an aspergilloma caused by an itraconazole-resistant strain of Aspergillus fumigatus, who was treated with voriconazole. The authors suggest that susceptibility testing of A. fumigatus strains is of value during long-term therapy with itraconazole, and that voriconazole may be a good option for treatment of patients infected with itraconazole-resistant strains of A. fumigatus.


The impact of age, ongoing task difficulty, and cue salience on preschoolers' prospective memory performance: the role of executive function.
The current study examined the impact of age, ongoing task (OT) difficulty, and cue salience on 4- and 5-year-old children's prospective memory (PM) and also explored the relation between individual differences in executive function (working memory, inhibition, and shifting) and PM. OT difficulty and cue salience are predicted to affect the detection of PM cues based on the multiprocess framework, yet neither has been thoroughly investigated in young children. OT difficulty was manipulated by requiring children to sort cards according to the size of pictured items (easy) or by opposite size (difficult), and cue salience was manipulated by placing a red border around half of the target cues (salient) and no border around the other cues (non-salient). The 5-year-olds outperformed the 4-year-olds on the PM task, and salient PM cues resulted in better PM cues compared with non-salient cues. There was no main effect of OT difficulty, and the interaction between cue salience and OT difficulty was not significant. However, a planned comparison revealed that the combination of non-salient cues and a difficult OT resulted in significantly worse PM performance than that in all of the other conditions. Inhibition accounted for significant variance in PM performance for non-salient cues and for marginally significant variance for salient cues. Furthermore, individual differences in inhibition fully mediated the effect of age on PM performance. Results are discussed in the context of the multiprocess framework and with reference to preschoolers' difficulty with the executive demands of dividing attention between the OT and PM task.


Functional Brain Stimulation in a Chronic Stroke Survivor With Moderate Impairment.
To determine the impact of transcranial direct current stimulation (tDCS) combined with repetitive, task-specific training (RTP) on upper-extremity (UE) impairment in a chronic stroke survivor with moderate impairment. The participant was a 54-yr-old woman with chronic, moderate UE hemiparesis after a single stroke that had occurred 10 yr before study enrollment. She participated in 45-min RTP sessions 3 days/wk for 8 wk. tDCS was administered concurrent to the first 20 min of each RTP session. Immediately after intervention, the participant demonstrated marked score increases on the UE section of the Fugl-Meyer Scale and the Motor Activity Log (on both the Amount of Use and the Quality of Movement subscales). These data support the use of tDCS combined with RTP to decrease impairment and increase UE use in chronic stroke patients with moderate impairment. This finding is crucial, given the paucity of efficacious treatment approaches in this impairment level.


Horizontal equity in health care utilization in Brazil, 1998-2008.
This study assesses trends in horizontal equity in the utilization of healthcare services from 1998 to 2008--a period of major economic and social change in Brazil. Data are from nationally representative surveys repeated in 1998, 2003, and 2008. We apply established methods for assessing horizontal inequity in healthcare access (the principle that people with the same healthcare needs should have similar access to healthcare services). Horizontal inequity is calculated as the difference between observed healthcare utilization and utilization predicted by healthcare needs. Outcomes examined include the probability of a medical, dental, or hospital visit during the past 12 months; any health service use in the past two weeks; and having a usual source of healthcare. We use monthly family income to measure differences in socioeconomic position. Healthcare needs include age, sex, self-rated health, and chronic conditions. Non-need factors include income, education, geography, health insurance, and Family Health Strategy coverage. The probability of having at least one doctor visit in the past 12 months became substantially more equitable over time, ending with a slightly pro-rich orientation in 2008. Any hospitalization in the past 12 months was found to be pro-poor in all periods but became slightly less so in 2008. Dental visits showed the largest absolute decrease in horizontal inequity, although they were still the most inequitably (pro-rich) distributed outcome in 2008. Service use in the past two weeks showed decreased inequity in 2003 but exhibited no significant change between 2003 and 2008. Having a usual source of care became less pro-rich over time and was nearly income-neutral by 2008. Factors associated with greater inequities include income, having a private health plan, and geographic location. Factors associated with greater equity included health needs, schooling, and enrolment in the Family Health Strategy. Healthcare utilization in Brazil appears to have become increasingly equitable over the past 10 years. Although this does not imply that equity in health outcomes has improved correspondingly, it does suggest that government policies aimed at increasing access, especially to primary care, have helped to make healthcare utilization in Brazil fairer over time.


Neutrophil Activation and Early Features of NET Formation Are Associated With Dengue Virus Infection in Human.
The involvement of the immune system in the protection and pathology of natural dengue virus (DENV) has been extensively studied. However, despite studies that have referred to activation of neutrophils in DENV infections, the exact roles of neutrophils remain elusive. Here, we explored the phenotypic and functional responses of neutrophils in a cohort of adult dengue patients. Results indicated that during an acute DENV infection, neutrophils up-regulate CD66b expression, and produce a more robust respiratory response as compared with that in convalescent or healthy individuals; this confirmed in vivo neutrophil activation during DENV infection. Spontaneous decondensation of nuclei, an early event of neutrophil extracellular trap (NET) formation, was also markedly increased in cells isolated from DENV-infected patients during the acute phase of the infection. In vitro incubation of NETs with DENV-2 virus significantly decreased DENV infectivity. Interestingly, increased levels of NET components were found in the serum of patients with more severe disease form-dengue hemorrhagic fever (DHF), but not uncomplicated dengue fever, during the acute phase of the infection. Levels of pro-inflammatory cytokines IL-8 and TNFα were also increased in DHF patients as compared with those in healthy and DF subjects. This suggested that NETs may play dual roles during DENV infection. The increased ability for NET formation during acute DENV infection appeared to be independent of PAD4-mediated histone H3 hyper-citrullination. Our study suggests that neutrophils are involved in immunological responses to DENV infection.


Mental Imagery, Impact, and Affect: A Mediation Model for Charitable Giving.
One of the puzzling phenomena in philanthropy is that people can show strong compassion for identified individual victims but remain unmoved by catastrophes that affect large numbers of victims. Two prominent findings in research on charitable giving reflect this idiosyncrasy: The (1) identified victim and (2) victim number effects. The first of these suggests that identifying victims increases donations and the second refers to the finding that people's willingness to donate often decreases as the number of victims increases. While these effects have been documented in the literature, their underlying psychological processes need further study. We propose a model in which identified victim and victim number effects operate through different cognitive and affective mechanisms. In two experiments we present empirical evidence for such a model and show that different affective motivations (donor-focused vs. victim-focused feelings) are related to the cognitive processes of impact judgments and mental imagery. Moreover, we argue that different mediation pathways exist for identifiability and victim number effects.


mtDNA polymorphism and metabolic inhibition affect sperm performance in conplastic mice.
Whereas a broad link exists between nucleotide substitutions in the mitochondrial genome (mtDNA) and a range of metabolic pathologies, exploration of the effect of specific mtDNA genotypes is on-going. Mitochondrial DNA mutations are of particular relevance for reproductive traits, since they are expected to have profound effects on male specific processes as a result of the strict maternal inheritance of mtDNA. Sperm motility is crucially dependent on ATP in most systems studied. However, the importance of mitochondrial function in the production of the ATP necessary for sperm function remains uncertain. In this study, we test the effect of mtDNA polymorphisms upon mouse sperm performance and bioenergetics by using five conplastic inbred strains that share the same nuclear background while differing in their mitochondrial genomes. We found that, while genetic polymorphisms across distinct mtDNA haplotypes are associated with modification in sperm progressive velocity, this effect is not related to ATP production. Furthermore, there is no association between the number of mtDNA polymorphisms and either (a) the magnitude of sperm performance decrease, or (b) performance response to specific inhibition of the main sperm metabolic pathways. The observed variability between strains may be explained in terms of additive effects of single nucleotide substitutions on mtDNA coding sequences, which have been stabilized through genetic drift in the different laboratory strains. Alternatively, the decreased sperm performance might have arisen from the disruption of the nuclear DNA/mtDNA interactions that have coevolved during the radiation of Mus musculus subspecies.


A stem structure in fibroblast growth factor receptor 2 transcripts mediates cell-type-specific splicing by approximating intronic control elements.
Alternative splicing of fibroblast growth factor receptor 2 (FGFR2) occurs in a cell-type-specific manner with the mutually exclusive use of exon IIIb or exon IIIc. Specific inclusion of exon IIIb is observed in epithelial cells, whereas exon IIIc inclusion is seen in mesenchymal cells. Epithelium-specific activation of exon IIIb and repression of exon IIIc are coordinately regulated by intronic activating sequence 2 (IAS2) and intronic splicing activator and repressor (ISAR) elements in FGFR2 pre-mRNA. Previously, it has been suggested that IAS2 and a 20-nucleotide core sequence of ISAR form a stem structure that allows for the proper regulation of FGFR2 alternative splicing. Replacement of IAS2 and the ISAR core with random sequences capable of stem formation resulted in the proper activation of exon IIIb and repression of exon IIIc in epithelial cells. Given the high degree of phylogenetic conservation of the IAS2-ISAR core structure and the fact that unrelated stem-forming sequences could functionally substitute for IAS2 and ISAR elements, we postulated that the stem structure facilitated the approximation of intronic control elements. Indeed, deletion of the entire stem-loop region and juxtaposition of sequences immediately upstream of IAS2 with sequences immediately downstream of the ISAR core maintained proper cell-type-specific inclusion of exon IIIb. These data demonstrate that IAS2 and the ISAR core are dispensable for the cell-type-specific activation of exon IIIb; thus, the major, if not the sole, role of the IAS2-ISAR stem in exon IIIb activation is to approximate sequences upstream of IAS2 with sequences downstream of the ISAR core. The downstream sequence is very likely a highly conserved GCAUG element, which we show was required for efficient exon IIIb activation.


Sociodemographic and behavioral characteristics of African-American women with HIV and AIDS in Los Angeles County, 1990-1997.
African-American women have the highest AIDS rate of any racial/ethnic group of women in both Los Angeles County (LAC), California and in the United States. Limited population-based epidemiologic studies of African-American women with HIV and AIDS describe this group and examine the factors associated with the excessive rates. Interview data collected from 1990 to 1997 on a population-based sample of AIDS cases and a group of HIV-infected women in LAC were analyzed to highlight the sociodemographic and behavioral characteristics of African-American women. This group of African-American women with HIV or AIDS in LAC were unemployed (88%), single mothers (64%), living on public assistance (86%) with annual household incomes <$10,000 U.S. (76%). A history of crack use predominated (50%). Compared with women of other races with HIV and AIDS, African-American women reported more sexual partners; reported more infections with sexually transmitted diseases; sought treatment for their HIV infection later; were more likely to trade sex; and were almost five times more likely to have ever used crack cocaine. HIV prevention for African-American women in LAC should focus on improving self-esteem and negotiation skills within the context of the crack cocaine culture and the disadvantaged social and economic situation described.


Evaluating more naturalistic outcome measures: A 1-year smartphone study in multiple sclerosis.
In this cohort of individuals with and without multiple sclerosis (MS), we illustrate some of the novel approaches that smartphones provide to monitor patients with chronic neurologic disorders in their natural setting. Thirty-eight participant pairs (MS and cohabitant) aged 18-55 years participated in the study. Each participant received an Android HTC Sensation 4G smartphone containing a custom application suite of 19 tests capturing participant performance and patient-reported outcomes (PROs). Over 1 year, participants were prompted daily to complete one assigned test. A total of 22 patients with MS and 17 cohabitants completed the entire study. Among patients with MS, low scores on PROs relating to mental and visual function were associated with dropout (p < 0.05). We illustrate several novel features of a smartphone platform. First, fluctuations in MS outcomes (e.g., fatigue) were assessed against an individual's ambient environment by linking responses to meteorological data. Second, both response accuracy and speed for the Ishihara color vision test were captured, highlighting the benefits of both active and passive data collection. Third, a new trait, a person-specific learning curve in neuropsychological testing, was identified using spline analysis. Finally, averaging repeated measures over the study yielded the most robust correlation matrix of the different outcome measures. We report the feasibility of, and barriers to, deploying a smartphone platform to gather useful passive and active performance data at high frequency in an unstructured manner in the field. A smartphone platform may therefore enable large-scale naturalistic studies of patients with MS or other neurologic diseases.


Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).
Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study). The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.


Uncertainty in cost-effectiveness analysis. Probabilistic uncertainty analysis and stochastic league tables.
Interest is growing in the application of standard statistical inferential techniques to the calculation of cost-effectiveness ratios (CER), but individual level data will not be available in many cases because it is very difficult to undertake prospective controlled trials of many public health interventions. We propose the application of probabilistic uncertainty analysis using Monte Carlo simulations, in combination with nonparametric bootstrapping techniques where appropriate. This paper also discusses how decision makers should interpret the CER of interventions where uncertainty intervals overlap. We show how the incorporation of uncertainty around costs and effects of interventions into a stochastic league table provides additional information to decision makers for priority setting. Stochastic league tables inform decision makers about the probability that a specific intervention would be included in the optimal mix of interventions for different resource levels, given the uncertainty surrounding the interventions.


Molecular characteristics of porcine alpha-synuclein splicing variants.
Alpha-synuclein (α-syn) is a 140 amino acid, intrinsically disordered protein with a potential role in neurotransmitter vesicle release. The protein is natively unfolded under physiological conditions, and is expressed predominantly in neural tissue. α-syn is associated with neuropathological conditions in Parkinson's disease, where the protein misfolds into oligomers and fibrils resulting in aggregates in Lewy bodies. Here we report the molecular cloning of SNCA cDNA encoding porcine α-syn and transcript variants hereof. Six transcripts coding for porcine α-syn are presented in the report, of which three result from exon skipping, generating in-frame splicing of coding exons 3 and 5. The splicing pattern of these alternative spliced variants is conserved between human and pig. All the observed in-frame deletions yield significantly shorter α-syn proteins compared with the 140 amino acid full-length protein. Expression analysis performed by real-time quantitative RT-PCR revealed a differential expression of the six transcript splicing variants in different pig organs and tissues. Common for all splicing variants, a very high transcript expression was detected in brain tissues and in spinal cord and very low or no expression outside the central nervous system. The porcine α-syn protein demonstrated markedly different biophysical characteristics compared with its human counterpart. No fibrillation of porcine α-syn was observed with the pig wild-type α-syn and A30P α-syn, and both variants show significantly reduced ability to bind to lipid vesicles. Overexpression of mutated porcine α-syn might recapitulate the human PD pathogenesis and lead to the identification of genetic modifiers of the disease.


Programmatic alcohol advertising, social media and public health: Algorithms, automated challenges to regulation, and the failure of public oversight.
Ongoing partnerships between transnational alcohol corporations and global social media platforms have transformed alcohol advertising in ways that undermine existing marketing regulations and threaten all forms of public oversight. In this paper I analyse this historic shift, arguing that new forms of programmatic alcohol advertising have emerged out of increasingly intensive processes of datafication on social media. Programmatic advertising is distinguished by increasing automation, turning advertising into a process of continually experimenting on the public to optimise advertising's "outputs", which now include conversions (sales). This experimental process relies on the delegation of agency to profit maximising, algorithmic machines that make alcohol advertising decisions with public health consequences. I contend that public health must now grapple with "algorithmic sovereignty": how private, corporate machines make decisions that challenge regulation and public oversight. Drawing on a case study of Meta's programmatic systems, I argue programmatic alcohol advertising exacerbates existing problems for the regulatory control of alcohol advertising on social media, while introducing entirely novel concerns. Machines make decisions in ways that are efficacious yet obscure, even to those who design and own them and to those who use them for marketing purposes. They allow for the maximisation of profit while obfuscating public oversight of the health impacts of alcohol advertising, and they make decisions in ways that are both predictive and pre-emptive, continuously nudging social media users towards consumption through altering, in real-time, the personalised content they encounter. This leaves established means for public oversight of alcohol marketing operating retrospectively while commodification of social life through alcohol advertising acts in the present to reshape the future. The machinic vision of programmatic alcohol advertising assesses social media users for their commercial utility, not as citizens with health needs, and may be producing evolving negative health outcomes that will only ever be understood in retrospect once their deleterious impact has become evident. Steps towards more effective public health interventions must begin with clearer recognition of these fundamental changes in advertising.


An exploratory study of Internet-initiated sexual offenses and the chat room sex offender: has the Internet enabled a new typology of sex offender?
This exploratory study examined 51 participants convicted of an Internet-initiated sex offense in which they attempted to entice an adolescent into a sexual relationship using an Internet chat room. All participants were convicted of a sex offense and subject to an evaluation as a part of sentencing requirements in Colorado. Clinical and behavioral data were obtained from each subject's offense-specific evaluation and chat room transcripts. The results of the study found that 90% of the participants were apprehended as a result of an Internet sex sting. The authors conclude that Internet chat room sex offenders constitute a separate group characterized by less severe criminogenic factors than other sex offenders (rapists, child molesters). It can be hypothesized that chat room sex offenders avoid relationships and spend a significant amount of time in online chat rooms as a primary social and sexual outlet, and engage in other sexually compulsive behaviors. Within this offender group, it was discovered that two subgroups exist: a contact-driven group motivated to engage in offline sexual behavior with an adolescent and a fantasy-driven group motivated to engage an adolescent in online cybersex without an express intent to meet offline. The chat room sex offender presents a significant clinical issue to treatment providers as a live victim does not exist. Thus, it is unclear if Internet sex stings prevent incidents of child sexual exploitation and may result in convictions of individuals who may never have abused a child. The data suggest a tentative sex offender typology, including subtypes, which need to be replicated in future studies.


Search performance of healthy adults on cancellation tests.
Cancellation tests are used extensively to identify visual search deficiencies in people with neurologic conditions, but little is known about how healthy adults perform on these tests. This study described the performance and types of search strategies used by healthy adults to complete cancellation tests from the Brain Injury Visual Assessment Battery for Adults. Study participants predominantly used structured left-to-right and top-to-bottom linear search patterns regardless of the configuration of the visual array. Other search qualities included (1) use of the same pattern throughout the search of an array, (2) symmetrical search of the array, and (3) rechecking performance on complex arrays. Older adult participants took more time to complete the tests than younger adults did. Knowing the strategies healthy adults use on cancellation tests enables therapists to identify visual search deficiencies in clients and design interventions to reestablish normal search strategies in daily occupations.


Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.
To evaluate the need for a randomised study of treatment of spinal osteoporosis with human parathyroid peptide in the secondary prevention of crush fractures; to study the effect of human parathyroid hormone peptide 1-34 plus sex hormones on vertebral body cancellous bone; and, separately, to determine the effect of relatively low doses of sodium fluoride plus calcium on spinal bone mineral density. Open study of patients with primary or postmenopausal osteoporosis. All patients had serial bone densitometry of the spine by quantitative computed tomography and dual photon absorptiometry as well as serial densitometry of the radial midshaft (cortical) and radial distal (trabecular) bone by quantitative computed tomography. Changes in the spinal bone not forming the spongiosa of the vertebral bodies ("cortical" bone) were determined from the difference between the two axial measurements, after correction to the same units of measurement. Northwick Park Hospital and Medical Research Council Clinical Research Centre. 24 Patients who fulfilled the conventional criteria for type 1 (vertebral) osteoporosis not secondary to recognised causes other than sex hormone deficiency and with at least one crush or wedge vertebral fracture and a spinal bone density (quantitative computed tomography) less than 80 mg/cm3 or two or more fractures. Twelve patients received human parathyroid peptide and 12 sodium fluoride; they were not randomised. Trends in axial and peripheral bone mass values determined by linear, time dependent regression analyses. The patients receiving the peptide showed a substantial increase in vertebral spongiosa (mean 25.6 mg/cm2 two years after the start of treatment). No significant changes were seen in spinal cortical or radial bone density. The patients receiving sodium fluoride showed roughly equal increases in cancellous and cortical bone over the same period (mean increase in vertebral spongiosa 16.1 mg/cm3). No significant changes were seen in radial bone. Treatment of postmenopausal women with human parathyroid peptide selectively increases spinal cancellous bone density by amounts that may prove useful in secondary prevention. Peptide treatment should now be tested in a randomised study in which the important end point is prevention of fractures as the usefulness of sodium fluoride in this context is doubtful.


What is the effect of treating secondary lymphedema after breast cancer with complete decongestive physiotherapy when the bandage is replaced with Kinesio Textape? - A pilot study.
Secondary lymphedema (SL) following breast cancer is a well-known complication following surgery or radiation. SL may result in loss of functional ability, cosmetic deformities, physical discomfort, recurrent episodes of erysipelas, and psychological distress. There is no evidence as to what is the most effective treatment for SL. This randomized controlled pilot study included 10 patients treated for SL following breast cancer. The patients were included and screened for SL by a physiotherapist. They were randomized to treatment with CDP with Kinesio Textape or bandage for 4 weeks. Endpoints were quality of life, circumference of the arm, costs, and working environment for the physiotherapist. The two groups were comparable according to baseline data. Outcomes on quality of life, costs, and working environment for the physiotherapist; the treatment with CDP with tape was superior to the CDP with bandage treatment. In regard to reducing the circumference there was no difference. This randomized controlled pilot study shows that CDP with tape can be an alternative to CDP with bandage. The quality of life is higher, the economy and working environment is better, and the effect measured by circumference is comparable. More RCTs are required to increase the evidence for CDP with tape. Treating lymphedema with CDP with tape after breast cancer is a good alternative to CDP with bandage and makes it possible to treat more patients with less resources.


Apple snack enriched with L-arginine using vacuum impregnation/ohmic heating technology.
Modern life has created a high demand for functional food, and in this context, emerging technologies such as vacuum impregnation and ohmic heating have been applied to generate functional foods. The aim of this research was to enrich the content of the semi-essential amino acid L-arginine in apple cubes using vacuum impregnation, conventional heating, and ohmic heating. Additionally, combined vacuum impregnation/conventional heating and vacuum impregnation/ohmic heating treatments were evaluated. The above treatments were applied at 30, 40 and 50 ℃ and combined with air-drying at 40 ℃ in order to obtain an apple snack rich in L-arginine. Both the impregnation kinetics of L-arginine and sample color were evaluated. The impregnated samples created using vacuum impregnation/ohmic heating at 50 ℃ presented a high content of L-arginine, an effect attributed primarily to electropermeabilization. Overall, vacuum impregnation/ohmic heating treatment at 50 ℃, followed by drying at 40 ℃, was the best process for obtaining an apple snack rich in L-arginine.


Fabrication of an integrated high-quality-factor (high-Q) optofluidic sensor by femtosecond laser micromachining.
We report on fabrication of a microtoroid resonator of a high-quality factor (i.e., Q-factor of ~3.24 × 10(6) measured under the critical coupling condition) integrated in a microfluidic channel using femtosecond laser three-dimensional (3D) micromachining. Coupling of light into and out of the microresonator has been realized with a fiber taper that is reliably assembled with the microtoroid. The assembly of the fiber to the microtoroid is achieved by welding the fiber taper onto the sidewall of the microtoroid using CO2 laser irradiation. The integrated microresonator maintains a high Q-factor of 3.21 × 10(5) as measured in air, which should still be sufficient for many sensing applications. We test the functionality of the integrated optofluidic sensor by performing bulk refractive index sensing of purified water doped with tiny amount of salt. It is shown that a detection limit of ~1.2 × 10(-4) refractive index unit can be achieved. Our result showcases the capability of integration of high-Q microresonators with complex microfluidic systems using femtosecond laser 3D micromachining.


Validating the Physiologic Model HumMod as a Substitute for Clinical Trials Involving Acute Normovolemic Hemodilution.
Blood conservation strategies and transfusion guidelines remain a heavily debated clinical topic. Previous investigational trials have shown that acute isovolemic hemodilution does not limit adequate oxygen delivery; however, a true critical hemoglobin level has never been investigated or defined due to safety concerns for human volunteers. Validated physiologic modeling may be useful to investigate hemodilution at critical hemoglobin levels without the ethical or safety hazards of clinical trials. Our hypothesis is that HumMod, an integrative physiological model, can replicate the cardiovascular and metabolic findings of previous clinical studies of acute isovolemic hemodilution and use coronary blood flow and coronary oxygen delivery in extreme hemodilution to predict a safety threshold. By varying cardiovascular and sizing parameters, unique individuals were generated to simulate a population using HumMod, an integrative mathematical model of human physiology. Hemodilution was performed by simultaneously hemorrhaging 500 mL aliquots of blood while infusing equal volumes of hetastarch, 5% albumin balanced salt solution, or triple volumes of lactated Ringer's solution over 10 minutes. Five hemodilution protocols reported over 3 studies were directly replicated with HumMod to compare and validate essential cardiovascular and metabolic responses to hemodilution in moderately healthy, awake adults. Cardiovascular parameters, mental status, arterial and mixed venous oxygen content, and oxyhemoglobin saturation were recorded after the removal of each aliquot. The outputs of this simulation were considered independent variables and were stratified by hemoglobin concentration at the time of measurement to assess hemoglobin as an independent predictor of hemodynamic and metabolic behavior. The published reports exhibited discrepancies: Weiskopf saw increased heart rate and cardiac index, while Jones and Ickx saw no change in these variables. In HumMod, arterial pressure was maintained during moderate hemodilution due to decreases in peripheral resistance opposing increases in cardiac index. HumMod showed preserved ventilation through moderate hemodilution, compensated for by an increased oxygen extraction similar to the studies of Jones and Ickx. The simulation results qualitatively followed the clinical studies, but there were statistical differences. In more extreme hemodilution, HumMod had a lesser increase in cardiac index, which led to deficiencies in oxygen delivery and low venous saturation. In the simulations, coronary blood flow and oxygen delivery increase up to a critical hemoglobin threshold of 55-75 g/L in HumMod. In this range, coronary blood flow and oxygen delivery fell, leading to cardiac injury. The allowable amount of hemodilution before reaching the critical point is most closely correlated with nonmuscle mass (r = 0.69) and resting cardiac output (r = 0.67). There were significant statistical differences in the model population and the clinical populations, but overall, the model responses lay within the clinical findings. This suggests our model is an effective replication of hemodilution in conscious, healthy adults. A critical hemoglobin range of 5.5-7.5 g/L was predicted and found to be highly correlated with nonmuscle mass and resting cardiac output.


Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice.
The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.


Relationship between quality of care and racial disparities in Medicare health plans.
Overall quality of care and racial disparities in quality are important and related problems in health care, but their relationship has not been well studied. In the Medicare managed care program, broad improvements in quality have been accompanied by reduced racial gaps in processes of care, but substantial disparities in outcomes have persisted. To assess variations among Medicare health plans in overall quality and racial disparity in 4 Health Plan Employer and Data Information Set (HEDIS) outcome measures, to determine whether high-performing plans exhibit smaller racial disparities, and to identify plans with high quality and low disparity. We assessed the relationship between quality and racial disparity using multilevel multivariable regression models. The study sample included 431,573 individual-level observations in 151 Medicare health plans from 2002 to 2004. Hemoglobin A(1c) of less than 9.5% or less than 9.0% for enrollees with diabetes; low-density lipoprotein cholesterol level of less than 130 mg/dL for enrollees with diabetes or after a coronary event; and blood pressure of less than 140/90 mm Hg for enrollees with hypertension. Clinical performance on HEDIS outcome measures was 6.8% to 14.4% lower for black enrollees than for white enrollees (P<.001 for all). For each measure, more than 70% of this disparity was due to different outcomes for black and white individuals enrolled in the same health plan rather than selection of black enrollees into lower-performing plans. Health plans varied substantially in both overall quality and racial disparity on each of the 4 outcome measures. Adjusted correlations between overall quality and racial disparity were small and not statistically significant, ranging from 0.01 (blood pressure control) to -0.21 (cholesterol control in diabetes). Only 1 health plan achieved both high quality and low disparity on more than 1 measure. In Medicare health plans, disparities vary widely and are only weakly correlated with the overall quality of care. Therefore, plan-specific performance reports of racial disparities on outcome measures would provide useful information not currently conveyed by standard HEDIS reports.


The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine Metabolism on Daily Nicotine Exposure in African American Smokers.
African American (AA) smokers experience greater tobacco-related disease burden than Whites, despite smoking fewer cigarettes per day (CPD). Understanding factors that influence daily nicotine intake in AA smokers is an important step toward decreasing tobacco-related health disparities. One factor of interest is smoking topography, or the study of puffing behavior. (i) to create a model using puff characteristics, nicotine dependence, and nicotine metabolism to predict daily nicotine exposure, and (ii) to compare puff characteristics and nicotine intake from two cigarettes smoked at different times to ensure the reliability of the puff characteristics included in our model. Sixty AA smokers smoked their preferred brand of cigarette at two time points through a topography device. Plasma nicotine, expired CO, and changes in subjective measures were measured before and after each cigarette. Total nicotine equivalents (TNE) was measured from 24-hour urine collected during ad libitum smoking. In a model predicting daily nicotine exposure, total puff volume, CPD, sex, and menthol status were significant predictors (R(2) = 0.44, P < 0.001). Total puff volume was significantly greater and inter-puff intervals were significantly shorter after ad lib smoking compared with the first cigarette of the day, but puffing behaviors for both cigarettes were highly correlated (r range = 0.69-0.89, P < 0.001) within-subjects. This is the first study, to our knowledge, to show that puff characteristics of individual cigarettes are predictive of daily nicotine intake. These findings enhance our understanding of the relationship between smoking behavior and nicotine intake in AA smokers. Cancer Epidemiol Biomarkers Prev; 25(6); 936-43. ©2016 AACR.


1976 and 2009 H1N1 influenza virus vaccines boost anti-hemagglutinin stalk antibodies in humans.
Infection with pandemic H1N1 influenza A viruses (IAVs) containing hemagglutinin (HA) proteins with globular heads that differ substantially from seasonal strains results in a boost in broadly cross-reactive antibodies that bind to the HA stalk. Boosting these antibodies has become an attractive strategy for creating a universal IAV vaccine. Therefore, it was essential to determine whether vaccines containing H1N1 viruses whose head domains differ substantially compared to seasonal strains could also achieve this boost. Prospective samples of subjects who had received the A/New Jersey/1976 (NJ/76) vaccine and healthy, age-matched controls were assessed for the presence of anti-HA stalk antibodies before and after receiving the A/California/04/2009 (Cal/09) vaccine between October 2009 and January 2010. Individuals who received either the NJ/76 vaccine or the Cal/09 vaccine experienced a robust boost in HA stalk-reactive, neutralizing antibodies similar to what has been observed in individuals infected with Cal/09. These results demonstrate that vaccines containing viruses whose HA head domains that differ substantially from seasonal strains are capable of boosting titers of HA stalk antibodies. Furthermore, anti-HA stalk antibodies elicited by vaccination appear to be long-lived and therefore could be targeted for the generation of a universal IAV vaccine.


Clonal dissemination of mupirocin-resistant staphylococci in Greek hospitals.
To determine the rates of mupirocin resistance in staphylococci during a 4 year period (1999-2002) in Greece. A total of 1200 Staphylococcus aureus and 2760 coagulase-negative staphylococci (CoNS), consecutively collected from four Greek hospitals located in different geographical areas, were tested for susceptibility to mupirocin using the Etest and a reference agar dilution method. Twenty-four S. aureus (2%) and 532 CoNS (19.2%) were found to be mupirocin-resistant during the study period. High-level mupirocin resistance was detected in 20 S. aureus (1.6%) and in 440 CoNS (15.9%), respectively. No variations in the rates of mupirocin-resistant S. aureus in relation to the year of collection were observed. In contrast, the rate of mupirocin-resistant CoNS increased dramatically from 9% in 1999, to 14% in 2000, 20% in 2001 and reached 33% in 2002. PFGE analysis revealed the presence of one main clone (A) among mupirocin-resistant S. aureus and two main clones (i and a) among Staphylococcus epidermidis isolates. In Greece, the rate of mupirocin-resistant S. aureus has remained low and steady since 1999. The high rate of mupirocin-resistant CoNS (33%) in 2002 was due mainly to clonal dissemination of epidemic hospital clones.


CRISPR Correction of Duchenne Muscular Dystrophy.
The ability to efficiently modify the genome using CRISPR technology has rapidly revolutionized biology and genetics and will soon transform medicine. Duchenne muscular dystrophy (DMD) represents one of the first monogenic disorders that has been investigated with respect to CRISPR-mediated correction of causal genetic mutations. DMD results from mutations in the gene encoding dystrophin, a scaffolding protein that maintains the integrity of striated muscles. Thousands of different dystrophin mutations have been identified in DMD patients, who suffer from a loss of ambulation followed by respiratory insufficiency, heart failure, and death by the third decade of life. Using CRISPR to bypass DMD mutations, dystrophin expression has been efficiently restored in human cells and mouse models of DMD. Here, we review recent progress toward the development of possible CRISPR therapies for DMD and highlight opportunities and potential obstacles in attaining this goal.


Brazilian community health agents and qualitative primary healthcare information.
The aim of this study was to explore female community health agents' views about the value of recording qualitative information on contextual health issues they observe during home visits, data that are not officially required to be documented for the Brazilian System of Primary Healthcare Information. The study was conducted in community primary healthcare centres located in the cities of Araçatuba and Coroados (state of São Paulo) and Rio de Janeiro (state of Rio de Janeiro), Brazil. The design was a qualitative, exploratory study. The purposeful sampling criteria were being female, with a minimum of three years of continuous service in the same location. Data collection with 62 participants was conducted via 11 focus groups (in 2007 and 2008). Audio files were transcribed and submitted to the method of thematic analysis. Four themes guided the analysis: working with qualitative information and undocumented observation; reflecting on qualitative information; integrating/analysing quantitative and qualitative information; and information-sharing with agents and family health teams. In 2010, 25 community health agents verified the final interpretation of the findings. Participants valued the recording of qualitative, contextual information to expand understanding of primary healthcare issues and as an indicator of clients' improved health behaviour and health literacy. While participants initiated the recording of additional health information, they generally did not inform the family health team about these findings. They perceived that team members devalued this type of information by considering it a reflection of the clientele's social conditions or problems beyond the scope of medical concerns. Documentation of qualitative evidence can account for the effectiveness of health education in two ways: by improving preventative care, and by amplifying the voices of underprivileged clients who live in poverty to ensure the most appropriate and best quality primary healthcare for them.


NMDA receptor antagonists can enhance or impair learning performance in animals.
The effects of NMDA receptor antagonism on learning and memory were investigated using competitive (DL-2-amino-7-phosphonoheptanoate, AP7) and non-competitive (MK 801) blockers in three different learning tasks. Administration (i.p.) of drugs prior to training resulted in impaired learning performance in the place-navigation and dark-avoidance paradigms, and improved performance in the step-down passive avoidance task; however, using this treatment protocol, the possibility of drug-induced non-mnemonic effects modifying learning performance could not be excluded. Drug administration immediately post-trial had no effect in the place-navigation paradigm, and improved retention performance in the dark-avoidance and step-down avoidance tasks. The similar results obtained with both types of antagonist indicate that the observed effects are indeed due to NMDA receptor blockade, and hence that such blockade modifies learning in a task-dependent manner. Exclusion of non-mnemonic effects by using the post-trial treatment regime demonstrates that NMDA antagonists facilitate learning of passive avoidance tasks.


[Depression in the aged: preliminary evaluation of the effectiveness, as an screening instrument, of the 5-item version of the Geriatric Depression Scale].
The best approach to improve under-recognition of depression is routine screening, ideally using an instrument that is highly effective and easy to administer. To test the effectiveness of the 5-item version of the Geriatric Depression Scale (5-GDS) for depression screening in a community-dwelling Chilean elderly population. 110 subjects were evaluated at the geriatric outpatient clinic of a university teaching hospital. Patients answered a questionnaire that included the Geriatric Depression Scale (GDS), and demographic information. Using the 15-item GDS score as reference standard to classify subjects as depressed, test characteristics of the 5-GDS were evaluated. Subjects had a mean 15-item GDS score of 5.4; 47% classified as depressed. Depressed and not depressed subjects were similar with regard to demographics, educational level and comorbid conditions. The mean score was 1.9 for the 5-item GDS. Pearson correlation for 15-item and 5-item GDS scores was 0.92, p < 0.001. Using 15-item GDS score as reference standard, the 5-item GDS had a sensitivity of 0.88, specificity 0.90, positive predictive value 0.88 and negative predictive value 0.90. The 5-item GDS seems to be a promising screening tool for depression. If revalidated against clinical evaluation, it might be the preferred screening tool for depression in the Chilean community-dwelling elderly.


Folding sticky elastica: dynamics and reversibility of folds in Langmuir monolayers.
Lipid monolayers at the air/water interface are often subject to large mechanical stresses when compressed laterally. For large enough compression they fold in the out-of-plane direction to relax stress. The repetitive folding and unfolding of lung surfactant monolayers during breathing plays a critical role in conserving monolayer material at the air/water interface lining the lung. Although the mechanisms behind the folding have been explored recently, relatively little information exists regarding the implications of folding dynamics on the long-term stability of the monolayer. We address this question by investigating the dynamical effect of folding rate in a lipid monolayer containing nano-particles, using a combination of analytic theory, simulation and experiment. We find that the presence of adsorbed particles are essential for monolayer rupture during unfolding. These particles act as linkers pinning the folds shut. The rate of folding affects reversibility as well. We construct a reversibility phase diagram spanned by the compression period and the size of the adsorbed particles showing the complex interaction of fold morphology, particle diffusion, and linker unbinding that results in reversible or irreversible folding.


Mannan structural complexity is decreased when Candida albicans is cultivated in blood or serum at physiological temperature.
The Candida albicans cell wall provides an architecture that allows for the organism to survive environmental stress as well as interaction with host tissues. Previous work has focused on growing C. albicans on media such as Sabouraud or YPD at 30°C. Because C. albicans normally colonizes a host, we hypothesized that cultivation on blood or serum at 37°C would result in structural changes in cell wall mannan. C. albicans SC5314 was inoculated onto YPD, 5% blood, or 5% serum agar media three successive times at 30°C and 37°C, then cultivated overnight at 30°C in YPD. The mannan was extracted and characterized using 1D and 2D (1)H NMR techniques. At 30°C cells grown in blood and serum contain less acid-stable terminal β-(1→2)-linked d-mannose and α-(1→2)-linked d-mannose-containing side chains, while the acid-labile side chains of mannan grown in blood and serum contain fewer β-Man-(1→2)-α-Man-(1→ side chains. The decrement in acid-stable mannan side chains is greater at 37°C than at 30°C. Cells grown on blood at 37°C show fewer →6)-α-Man-(1→ structural motifs in the acid-stable polymer backbone. The data indicate that C. albicans, grown on media containing host-derived components, produces less complex mannan. This is accentuated when the cells are cultured at 37°C. This study demonstrates that the C. albicans cell wall is a dynamic and adaptive organelle, which alters its structural phenotype in response to growth in host-derived media at physiological temperature.


Multiphoton laser direct writing of two-dimensional silver structures.
We report a novel and efficient method for the laser direct writing of two-dimensional silver structures. Multiphoton absorption of a small fraction of the output of a Ti:sapphire oscillator is sufficient to photoreduce silver nitrate in a thin film of polyvinylpyrrolidone that has been spin-coated on a substrate. The polymer can then be washed away, leaving a pattern consisting of highly interconnected silver nanoparticles. We report the characterization of the silver patterns using scanning electron and atomic force microscopies, and demonstrate the application of this technique in the creation of diffraction gratings.


Persistent cannabis users show neuropsychological decline from childhood to midlife.
Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health. Concomitantly, adolescents are initiating cannabis use at younger ages, and more adolescents are using cannabis on a daily basis. The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users. Participants were members of the Dunedin Study, a prospective study of a birth cohort of 1,037 individuals followed from birth (1972/1973) to age 38 y. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. Neuropsychological testing was conducted at age 13 y, before initiation of cannabis use, and again at age 38 y, after a pattern of persistent cannabis use had developed. Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, even after controlling for years of education. Informants also reported noticing more cognitive problems for persistent cannabis users. Impairment was concentrated among adolescent-onset cannabis users, with more persistent use associated with greater decline. Further, cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users. Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents.