Urban-rural differences in psychological distress in nine countries of the former Soviet Union.
Studies have shown that the prevalence of mental illness can vary between urban and rural locations. This study extended research to the countries of the former Soviet Union (fSU) by assessing the association between settlement type and psychological distress and whether factors associated with psychological distress vary by settlement type. Data on 18,000 adults aged ≥18 years from the Health in Times of Transition (HITT) survey undertaken in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, and Ukraine in 2010/11 were analyzed. Settlement types were country capitals, regional capitals, cities/other urban settlements, and villages. Psychological distress was defined as the country-specific highest quintile of a composite score based on 11 questions. Logistic regression analysis with random effects was used to examine associations. In a pooled country analysis, living in a smaller urban settlement or village was associated with significantly higher odds for psychological distress compared to living in the country capital. Lower social support was a strong correlate of psychological distress in all locations except capital cities. The psychological distress measure has not been formally validated in the study countries. Lower levels of urbanicity are associated with greater psychological distress in the fSU countries. As many Western studies have linked greater urbanization to poorer mental health, this highlights the need for caution in extrapolating findings from one part of the world to others and the importance of undertaking research on the geographical correlates of mental health in different world regions.


Transcriptome sequencing and comparative analysis of cucumber flowers with different sex types.
Cucumber, Cucumis sativus L., is an economically and nutritionally important crop of the Cucurbitaceae family and has long served as a primary model system for sex determination studies. Recently, the sequencing of its whole genome has been completed. However, transcriptome information of this species is still scarce, with a total of around 8,000 Expressed Sequence Tag (EST) and mRNA sequences currently available in GenBank. In order to gain more insights into molecular mechanisms of plant sex determination and provide the community a functional genomics resource that will facilitate cucurbit research and breeding, we performed transcriptome sequencing of cucumber flower buds of two near-isogenic lines, WI1983G, a gynoecious plant which bears only pistillate flowers, and WI1983H, a hermaphroditic plant which bears only bisexual flowers. Using Roche-454 massive parallel pyrosequencing technology, we generated a total of 353,941 high quality EST sequences with an average length of 175bp, among which 188,255 were from gynoecious flowers and 165,686 from hermaphroditic flowers. These EST sequences, together with approximately 5,600 high quality cucumber EST and mRNA sequences available in GenBank, were clustered and assembled into 81,401 unigenes, of which 28,452 were contigs and 52,949 were singletons. The unigenes and ESTs were further mapped to the cucumber genome and more than 500 alternative splicing events were identified in 443 cucumber genes. The unigenes were further functionally annotated by comparing their sequences to different protein and functional domain databases and assigned with Gene Ontology (GO) terms. A biochemical pathway database containing 343 predicted pathways was also created based on the annotations of the unigenes. Digital expression analysis identified approximately 200 differentially expressed genes between flowers of WI1983G and WI1983H and provided novel insights into molecular mechanisms of plant sex determination process. Furthermore, a set of SSR motifs and high confidence SNPs between WI1983G and WI1983H were identified from the ESTs, which provided the material basis for future genetic linkage and QTL analysis. A large set of EST sequences were generated from cucumber flower buds of two different sex types. Differentially expressed genes between these two different sex-type flowers, as well as putative SSR and SNP markers, were identified. These EST sequences provide valuable information to further understand molecular mechanisms of plant sex determination process and forms a rich resource for future functional genomics analysis, marker development and cucumber breeding.


Controlling the Size of Two-Dimensional Polymer Platelets for Water-in-Water Emulsifiers.
A wide range of biorelevant applications, particularly in pharmaceutical formulations and the food and cosmetic industries, require the stabilization of two water-soluble blended components which would otherwise form incompatible biphasic mixtures. Such water-in-water emulsions can be achieved using Pickering stabilization, where two-dimensional (2D) nanomaterials are particularly effective due to their high surface area. However, control over the shape and size of the 2D nanomaterials is challenging, where it has not yet been possible to examine chemically identical nanostructures with the same thickness but different surface areas to probe the size-effect on emulsion stabilization ability. Hence, the rationale design and realization of the full potential of Pickering water-in-water emulsion stabilization have not yet been achieved. Herein, we report for the first time 2D poly(lactide) platelets with tunable sizes (with varying coronal chemistry) and of uniform shape using a crystallization-driven self-assembly methodology. We have used this series of nanostructures to explore the effect of 2D platelet size and chemistry on the stabilization of a water-in-water emulsion of a poly(ethylene glycol) (PEG)/dextran mixture. We have demonstrated that cationic, zwitterionic, and neutral large platelets (ca. 3.7 × 106 nm2) all attain smaller droplet sizes and more stable emulsions than their respective smaller platelets (ca. 1.2 × 105 nm2). This series of 2D platelets of controlled dimensions provides an excellent exemplar system for the investigation of the effect of just the surface area on the potential effectiveness in a particular application.


Furan-oxidation-triggered inducible DNA cross-linking: acyclic versus cyclic furan-containing building blocks--on the benefit of restoring the cyclic sugar backbone.
Oligodeoxynucleotides incorporating a reactive functionality can cause irreversible cross-linking to the target sequence and have been widely studied for their potential in inhibition of gene expression or development of diagnostic probes for gene analysis. Reactive oligonucleotides further show potential in a supramolecular context for the construction of nanometer-sized DNA-based objects. Inspired by the cytochrome P450 catalyzed transformation of furan into a reactive enal species, we recently introduced a furan-oxidation-based methodology for cross-linking of nucleic acids. Previous experiments using a simple acyclic building block equipped with a furan moiety for incorporation into oligodeoxynucleotides have shown that cross-linking occurs in a very fast and efficient way and that substantial amounts of stable, site-selectively cross-linked species can be isolated. Given the destabilization of duplexes observed upon introduction of the initially designed furan-modified building block into DNA duplexes, we explore here the potential benefits of two new building blocks featuring an extended aromatic system and a restored cyclic backbone. Thorough experimental analysis of cross-linking reactions in a series of contexts, combined with theoretical calculations, permit structural characterization of the formed species and allow assessment of the origin of the enhanced cross-link selectivity. Our experiments clearly show that the modular nature of the furan-modified building blocks used in the current cross-linking strategy allow for fine tuning of both yield and selectivity of the interstrand cross-linking reaction.


Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis.
Patients with diabetes mellitus are at increased risk of developing cardiovascular disease. Controlling lipid levels has a preventive effect on the occurrence of major cardiovascular and cerebrovascular events. Individual trials have shown varying data on the efficacy of treatment with lipid-lowering statin therapy in the primary prevention of such events in diabetes. The objective of this study was to assess the efficacy of statins in the primary prevention of the first-time occurrence of a major cardiovascular or cerebrovascular event in diabetic patients. Secondary endpoints were fatal/non-fatal stroke, fatal/non-fatal myocardial infarction and all-cause mortality. A systematic search for trial reports was conducted in PubMed, EMBASE, The Cochrane library and clinicaltrials.gov for the years 1966-2011. Reference lists of reviews and meta-analyses of related subjects were searched. High-quality, randomized, double-blinded clinical trials comparing a statin with placebo for the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients were selected. Only large studies with a minimum of 500 diabetic participants followed-up for at least 2 years were included. Endpoints were major cardiovascular and cerebrovascular events. Trial and patient characteristics were extracted by three researchers. The quality of the included studies was tested with the Jadad score. The combined effect on primary as well as secondary endpoints was measured with a fixed-effect model. Publication bias was examined with a funnel plot. Four trials were included, for a total of 10,187 participants. Treatment with statins in the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients resulted in a significant relative risk (RR) reduction in the first-time occurrence of major cardiovascular or cerebrovascular events (RR 0.75, 95% CI 0.67-0.85), fatal/non-fatal stroke (RR 0.69, 95% CI 0.51-0.92) and fatal/non-fatal myocardial infarction (RR 0.70, 95% CI 0.54-0.90) and a non-significant RR reduction in all-cause mortality (RR 0.84, 95% CI 0.65-1.09). Among the studies there was non-significant heterogeneity in the individual effect estimates and no publication bias. Exclusion criteria and endpoints varied slightly between studies. The type and dosing of statin therapy differed between studies. Non-compliance in the statin treatment group and the use of statin treatment in the placebo group could have led to lower risk reductions. Treatment with statins in primary prevention among diabetic patients has a significant beneficial effect on event rates of the first-time occurrence of a major cardiovascular or cerebrovascular event, fatal/non-fatal stroke and fatal/non-fatal myocardial infarction. There was a non-significant RR reduction in all-cause mortality.


FDG-PET in cardiac infections.
Cardiac infections include a group of conditions involving the heart muscle, the pericardium, or the endocardial surface of the heart. Infections can extend to prosthetic material or the leads in case of the implantation of devices. Despite their relative low incidence, these conditions that are associated with high morbidity and mortality involve a relevant burden of diagnostic workup. Early diagnosis is crucial for adequate management of patient, as early treatment improves the prognosis; unfortunately, the clinical manifestations are often nonspecific. Accurate and timely diagnosis typically requires the correlation of imaging findings with laboratory data. (18)F-FDG-PET is a well-established imaging modality for the diagnosis and management of malignancies, and evidence is also increasing regarding its value for assessing infectious and inflammatory diseases. This article summarizes published evidence on the usefulness of (18)F-FDG-PET for the diagnosis of cardiac infections, mainly focused on endocarditis and cardiovascular device infections. Nevertheless, the diagnostic potential of (18)F-FDG-PET in patients with pericarditis and myocarditis is also briefly reviewed, considering the most likely future advances and new perspectives that the use of PET/magnetic resonance would open in the diagnosis of such conditions.


Neural mechanism in anterior prefrontal cortex for inhibition of prolonged set interference.
Once one cognitive set dominates our behavior, it continues to influence subsequent behavior for a while even after a task to be performed is changed to another. Despite abundant knowledge of the inhibitory mechanisms that are recruited at the first trial after the change (the first inhibition trial), little is known about the inhibition of prolonged proactive interference from a previous set that lingers for several trials after the first inhibition trial. The present functional MRI study explored the neural mechanisms for inhibition of a previous set that were recruited after the first inhibition trial. A modified Wisconsin Card Sorting Test was used where "dual-match stimuli" were intermittently presented and allowed subjects to perform correctly based on previously appropriate, now inappropriate, responses. In response to the dual-match stimulus at "release" trials presented after the first inhibition trials, the subjects were transiently exempted from inhibiting the prolonged previous set. As expected from the exempted inhibitory demands, significant reaction time decrease was revealed in the release trials. Consistent with the behavioral results, transient signal decrease time-locked to the release trials was revealed in the left anterior part of the superior frontal sulcus. Moreover, the anterior prefrontal region was not sensitive to the task change, which exhibited a marked contrast to the left posterior inferior prefrontal region that showed significant signal changes in both events. These results revealed multiple inhibitory mechanisms in the lateral prefrontal cortex that are recruited in different temporal contexts of the interference from a previous cognitive set.


[Lung cancer in a female non-smoker with occupational exposure to asbestos: a case report].
Until recently, asbestos was widely used in a variety of industrial processes. Workers exposed to asbestos may develop lung and pleural diseases such as asbestosis, lung cancer, benign pleural effusion, pleural plaques and mesothelioma. To describe a clinical case of lung cancer in a female non-smoker with occupational exposure to asbestos. The clinical and occupational history was based on the information kindly provided by the Occupational Unit of the National Health Service and on the case history of a hospital admittance in 2001, when the patient underwent surgery for lung cancer. The patient worked for 6 years in an asbestos manufacturing industry where she was exposed to high concentrations of asbestos, and then worked for 14 years in a sugar refinery only during the summer. She had benign pleural effusion, pleural plaques, asbestosis and lung cancer. We concluded that a six-year exposure to high doses of asbestos may induce lung cancer and asbestosis in a female non-smoker.


Experimental and theoretical studies on the rearrangement of 2-oxoazepane α,α-amino acids into 2'-oxopiperidine β(2,3,3) -amino acids: an example of intramolecular catalysis.
Enantiopure β-amino acids represent interesting scaffolds for peptidomimetics, foldamers and bioactive compounds. However, the synthesis of highly substituted analogues is still a major challenge. Herein, we describe the spontaneous rearrangement of 4-carboxy-2-oxoazepane α,α-amino acids to lead to 2'-oxopiperidine-containing β(2,3,3) -amino acids, upon basic or acid hydrolysis of the 2-oxoazepane α,α-amino acid ester. Under acidic conditions, a totally stereoselective synthetic route has been developed. The reordering process involved the spontaneous breakdown of an amide bond, which typically requires strong conditions, and the formation of a new bond leading to the six-membered heterocycle. A quantum mechanical study was carried out to obtain insight into the remarkable ease of this rearrangement, which occurs at room temperature, either in solution or upon storage of the 4-carboxylic acid substituted 2-oxoazepane derivatives. This theoretical study suggests that the rearrangement process occurs through a concerted mechanism, in which the energy of the transition states can be lowered by the participation of a catalytic water molecule. Interestingly, it also suggested a role for the carboxylic acid at position 4 of the 2-oxoazepane ring, which facilitates this rearrangement, participating directly in the intramolecular catalysis.


Predicting smoking status by symptoms of depression for U.S. adolescents.
This study examined the predictive relationships between adolescents' smoking and symptoms of depression. A national sample of 6,900 adolescents, ages 14 to 18 years, were selected for analysis. Variables of interest included measures for smoking status and symptoms of depression. Odds ratio and adjusted odds ratio from logistic regression analyses indicated that more of the 885 smokers than of the 6,015 nonsmokers reported feelings of unhappiness, sadness, or depression, hopelessness about the future, and having trouble going to sleep.


Nicotine-Induced Conditional Place Preference Is Affected by Head Injury: Correlation with Dopamine Release in the Nucleus Accumbens Shell.
Traumatic brain injury is known to impact dopamine-mediated reward pathways, but the underlying mechanisms have not been fully established. Nicotine-induced conditional place preference was used to study rats exposed to a 6-psi fluid percussion injury with and without prior exposure to nicotine. Preference was quantified as a score defined as (C1 - C2) / (C1 + C2), where C1 is time in the nicotine-paired compartment and C2 is time in the saline-paired compartment. Subsequent fast-scan cyclic voltammetry was used to analyze the impact of nicotine infusion on dopamine release in the shell portion of the nucleus accumbens. To further determine the influence of brain injury on nicotine withdrawal, nicotine infusion was administered to the rats after fluid percussion injury. The effects of fluid percussion injury on conditional place preference after prior exposure to nicotine and abstinence or withdrawal from nicotine were also assessed. After traumatic brain injury, dopamine release was reduced in the nucleus accumbens shell, and nicotine-induced conditional place preference preference was significantly impaired. Preference scores of control, sham-injured, and fluid percussion injury groups were 0.1627±0.04204, 0.1515±0.03806, and -0.001300±0.04286, respectively. Nicotine-induced conditional place preference was also seen in animals after nicotine pretreatment, with a conditional place preference score of 0.07805±0.02838. Nicotine preexposure substantially increased tonic dopamine release in sham-injured animals, but it did not change phasic release; nicotine exposure after fluid percussion injury enhanced phasic release, though not to the same levels seen in sham-injured rats. Conditioned preference was related not only to phasic dopamine release (r=0.8110) but also to the difference between tonic and phasic dopamine levels (r=0.9521). Traumatic brain injury suppresses dopamine release from the shell portion of the nucleus accumbens, which in turn significantly alters reward-seeking behavior. These results have important implications for tobacco and drug use after traumatic brain injury.


Interactive rendering of acquired materials on dynamic geometry using frequency analysis.
Shading acquired materials with high-frequency illumination is computationally expensive. Estimating the shading integral requires multiple samples of the incident illumination. The number of samples required may vary across the image, and the image itself may have high- and low-frequency variations, depending on a combination of several factors. Adaptively distributing computational budget across the pixels for shading is a challenging problem. In this paper, we depict complex materials such as acquired reflectances, interactively, without any precomputation based on geometry. In each frame, we first estimate the frequencies in the local light field arriving at each pixel, as well as the variance of the shading integrand. Our frequency analysis accounts for combinations of a variety of factors: the reflectance of the object projecting to the pixel, the nature of the illumination, the local geometry and the camera position relative to the geometry and lighting. We then exploit this frequency information (bandwidth and variance) to adaptively sample for reconstruction and integration. For example, fewer pixels per unit area are shaded for pixels projecting onto diffuse objects, and fewer samples are used for integrating illumination incident on specular objects.


Gelsolin-Cu/ZnSOD interaction alters intracellular reactive oxygen species levels to promote cancer cell invasion.
The actin-binding protein, gelsolin, is a well known regulator of cancer cell invasion. However, the mechanisms by which gelsolin promotes invasion are not well established. As reactive oxygen species (ROS) have been shown to promote cancer cell invasion, we investigated on the hypothesis that gelsolin-induced changes in ROS levels may mediate the invasive capacity of colon cancer cells.Herein, we show that increased gelsolin enhances the invasive capacity of colon cancer cells, and this is mediated via gelsolin's effects in elevating intracellular superoxide (O2.-) levels. We also provide evidence for a novel physical interaction between gelsolin and Cu/ZnSOD, that inhibits the enzymatic activity of Cu/ZnSOD, thereby resulting in a sustained elevation of intracellular O2.-. Using microarray data of human colorectal cancer tissues from Gene Omnibus, we found that gelsolin gene expression positively correlates with urokinase plasminogen activator (uPA), an important matrix-degrading protease invovled in cancer invasion. Consistent with the in vivo evidence, we show that increased levels of O2.- induced by gelsolin overexpression triggers the secretion of uPA. We further observed reduction in invasion and intracellular O2.- levels in colon cancer cells, as a consequence of gelsolin knockdown using two different siRNAs. In these cells, concurrent repression of Cu/ZnSOD restored intracellular O2.- levels and rescued invasive capacity.Our study therefore identified gelsolin as a novel regulator of intracellular O2.- in cancer cells via interacting with Cu/ZnSOD and inhibiting its enzymatic activity. Taken together, these findings provide insight into a novel function of gelsolin in promoting tumor invasion by directly impacting the cellular redox milieu.


Structures of the cGMP-dependent protein kinase in malaria parasites reveal a unique structural relay mechanism for activation.
The cyclic guanosine-3',5'-monophosphate (cGMP)-dependent protein kinase (PKG) was identified >25 y ago; however, efforts to obtain a structure of the entire PKG enzyme or catalytic domain from any species have failed. In malaria parasites, cooperative activation of PKG triggers crucial developmental transitions throughout the complex life cycle. We have determined the cGMP-free crystallographic structures of PKG from Plasmodium falciparum and Plasmodium vivax, revealing how key structural components, including an N-terminal autoinhibitory segment (AIS), four predicted cyclic nucleotide-binding domains (CNBs), and a kinase domain (KD), are arranged when the enzyme is inactive. The four CNBs and the KD are in a pentagonal configuration, with the AIS docked in the substrate site of the KD in a swapped-domain dimeric arrangement. We show that although the protein is predominantly a monomer (the dimer is unlikely to be representative of the physiological form), the binding of the AIS is necessary to keep Plasmodium PKG inactive. A major feature is a helix serving the dual role of the N-terminal helix of the KD as well as the capping helix of the neighboring CNB. A network of connecting helices between neighboring CNBs contributes to maintaining the kinase in its inactive conformation. We propose a scheme in which cooperative binding of cGMP, beginning at the CNB closest to the KD, transmits conformational changes around the pentagonal molecule in a structural relay mechanism, enabling PKG to orchestrate rapid, highly regulated developmental switches in response to dynamic modulation of cGMP levels in the parasite.


The Effect of Interdisciplinary Interventions on Risk Factors for Lifestyle Disease: A Literature Review.
Interventions that comprise interdisciplinary collaboration including behavioral elements are effective in addressing lifestyle disease risk factors. However, it is not known how best to conduct this collaboration for sustainable change. The aim of this study was to systematically examine the evidence for the effects of interdisciplinary interventions on lifestyle disease risk factors including weight, lipid levels, glycemic control, and blood pressure. To do so, a systematic review of the literature was conducted using the databases Scopus, Medline, and Web of Science (all years to September 2014). Eighteen articles describing 16 studies of interdisciplinary interventions were identified. Consistent results were found for effects on weight loss but not for effects on blood lipids, blood glucose, and blood pressure. Effective interventions involved collaborations between dieticians, exercise physiologists, and psychologists and incorporated intensive initial participant engagement. Few studies investigated the long-term effect of interventions, but where this was done, the maintenance of favorable changes required ongoing participant support. Current evidence suggests that interdisciplinary interventions are effective in promoting weight loss and that ongoing support of participants is key to maintaining results beyond initial study duration. Future studies should examine long-term effects in pragmatic trials that address translation to practice.


Carotid and vertebral injury study (CAVIS) technique for characterization of blunt traumatic aneurysms with reliability assessment.
Traumatic aneurysms occur in up to 20% of blunt traumatic extracranial carotid artery injuries. Currently there is no standardized method for characterization of traumatic aneurysms. For the carotid and vertebral injury study (CAVIS), a prospective study of traumatic cerebrovascular injury, we established a method for aneurysm characterization and tested its reliability. Saccular aneurysm size was defined as the greatest linear distance between the expected location of the normal artery wall and the outer edge of the aneurysm lumen ("depth"). Fusiform aneurysm size was defined as the "depth" and longitudinal distance ("length") paralleling the normal artery. The size of the aneurysm relative to the normal artery was also assessed. Reliability measurements were made using four raters who independently reviewed 15 computed tomographic angiograms (CTAs) and 13 digital subtraction angiograms (DSAs) demonstrating a traumatic aneurysm of the internal carotid artery. Raters categorized the aneurysms as either "saccular" or "fusiform" and made measurements. Five scans of each imaging modality were repeated to evaluate intra-rater reliability. Fleiss's free-marginal multi-rater kappa (κ), Cohen's kappa (κ), and interclass correlation coefficient (ICC) determined inter- and intra-rater reliability. Inter-rater agreement as to the aneurysm "shape" was almost perfect for CTA (κ = 0.82) and DSA (κ = 0.897). Agreements on aneurysm "depth," "length," "aneurysm plus parent artery," and "parent artery" for CTA and DSA were excellent (ICC > 0.75). Intra-rater agreement as to aneurysm "shape" was substantial to almost perfect (κ > 0.60). The CAVIS method of traumatic aneurysm characterization has remarkable inter- and intra-rater reliability and will facilitate further studies of the natural history and management of extracranial cerebrovascular traumatic aneurysms.


Hydrophilic interaction liquid chromatography method for measuring the composition of aquatic humic substances.
A hydrophilic interaction liquid chromatography (HILIC) method was developed to measure the composition of humic substances from river, reservoir, and treated wastewater based on their physicochemical properties. The current method fractionates the humic substances into four well-defined groups based on parallel analyses with a neutral and a cationic HILIC column, using mobile phases of varied compositions and pH. The results indicate that: (i) the proportion of carboxylic acids in the humic substances from terrestrial origins is less than half of that from treated wastewater (Jeddah, KSA), (ii) a higher content of basic compounds was observed in the humic substances from treated wastewater and Ribou Reservoir (Cholet, France) than in the sample from Loire River (France), (iii) a higher percentage of hydrophobic macromolecules were found in the humic substances from Loire River than in the other samples, and (iv) humic substances of treated wastewater contained less ionic neutral compounds (i.e., pKa 5-9) than the waters from terrestrial origins. The physicochemical property disparity amongst the compounds in each humic substances sample was also evaluated. The humic substances from the lightly humic Loire river displayed the highest disparity, whereas the highly humic Suwannee river (Georgia, USA) showed the most homogeneous humic substances.


The Bereaved Parent Needs Assessment: a new instrument to assess the needs of parents whose children died in the pediatric intensive care unit*.
To evaluate the reliability and validity of the Bereaved Parent Needs Assessment, a new instrument to measure parents' needs and need fulfillment around the time of their child's death in the pediatric intensive care unit. We hypothesized that need fulfillment would be negatively related to complicated grief and positively related to quality of life during bereavement. Cross-sectional survey. Five U.S. children's hospital pediatric intensive care units. Parents (n = 121) bereaved in a pediatric intensive care unit 6 months earlier. Surveys included the 68-item Bereaved Parent Needs Assessment, the Inventory of Complicated Grief, and the abbreviated version of the World Health Organization Quality of Life questionnaire. Each Bereaved Parent Needs Assessment item described a potential need and was rated on two scales: 1) a 5-point rating of importance (1 = not at all important, 5 = very important) and 2) a 5-point rating of fulfillment (1 = not at all met, 5 = completely met). Three composite scales were computed: 1) total importance (percentage of all needs rated ≥4 for importance), 2) total fulfillment (percentage of all needs rated ≥4 for fulfillment), and 3) percent fulfillment (percentage of important needs that were fulfilled). Internal consistency reliability was assessed by Cronbach's α and Spearman-Brown-corrected split-half reliability. Generalized estimating equations were used to test predictions between composite scales and the Inventory of Complicated Grief and World Health Organization Quality of Life questionnaire. Two items had mean importance ratings <3, and 55 had mean ratings >4. Reliability of composite scores ranged from 0.92 to 0.94. Total fulfillment was negatively correlated with Inventory of Complicated Grief (r = -.29; p < .01) and positively correlated with World Health Organization Quality of Life questionnaire (r = .21; p < .05). Percent fulfillment was also significantly correlated with both outcomes. Adjusting for parent's age, education, and loss of an only child, percent fulfillment remained significantly correlated with Inventory of Complicated Grief but not with World Health Organization Quality of Life questionnaire. The Bereaved Parent Needs Assessment demonstrated reliability and validity to assess the needs of parents bereaved in the pediatric intensive care unit. Meeting parents' needs around the time of their child's death may promote adjustment to loss.


Endogenous overexpression of Populus MYB186 increases trichome density, improves insect pest resistance, and impacts plant growth.
Trichomes are specialized epidermal cells that generally play a role in reducing transpiration and act as a deterrent to herbivory. In a screen of activation-tagged Populus tremula × Populus alba 717-1B4 trees, we identified a mutant line, fuzzy, with increased foliar trichome density. This mutant also had a 35% increase in growth rate and a 200% increase in the rate of photosynthesis as compared with wild-type poplar. The fuzzy mutant had significant resistance to feeding by larvae of the white-spotted tussock moth (Orgyia leucostigma), a generalist insect pest of poplar trees. The fuzzy trichome phenotype is attributable to activation tagging and increased expression of the gene encoding PtaMYB186, which is related to Arabidopsis thaliana MYB106, a known regulator of trichome initiation. The fuzzy phenotype can be recapitulated by overexpressing PtaMYB186 in poplar. PtaMYB186 overexpression results in reconfiguration of the poplar transcriptome, with changes in the transcript abundance of suites of genes that are related to trichome differentiation. It is notable that a plant with misexpression of a gene responsible for trichome development also had altered traits related to growth rate and pest resistance, suggesting that non-intuitive facets of plant development might be useful targets for plant improvement.


An Evaluation of Food as a Potential Source for Clostridium difficile Acquisition in Hospitalized Patients.
OBJECTIVE To determine whether Clostridium difficile is present in the food of hospitalized patients and to estimate the risk of subsequent colonization associated with C. difficile in food. METHODS This was a prospective cohort study of inpatients at a university-affiliated tertiary care center, May 9, 2011-July 12, 2012. Enrolled patients submitted a portion of food from each meal. Patient stool specimens and/or rectal swabs were collected at enrollment, every 3 days thereafter, and at discharge, and were cultured for C. difficile. Clinical data were reviewed for evidence of infection due to C. difficile. A stochastic, discrete event model was developed to predict exposure to C. difficile from food, and the estimated number of new colonization events from food exposures per 1,000 admissions was determined. RESULTS A total of 149 patients were enrolled and 910 food specimens were obtained. Two food specimens from 2 patients were positive for C. difficile (0.2% of food samples; 1.3% of patients). Neither of the 2 patients was colonized at baseline with C. difficile. Discharge colonization status was available for 1 of the 2 patients and was negative. Neither was diagnosed with C. difficile infection while hospitalized or during the year before or after study enrollment. Stochastic modeling indicated contaminated hospital food would be responsible for less than 1 newly colonized patient per 1,000 hospital admissions. CONCLUSIONS The recovery of C. difficile from the food of hospitalized patients was rare. Modeling suggests hospital food is unlikely to be a source of C. difficile acquisition. Infect Control Hosp Epidemiol 2016;1401-1407.


A combinatorial radiographic phenotype may stratify patient survival and be associated with invasion and proliferation characteristics in glioblastoma.
Individual MRI characteristics (e.g., volume) are routinely used to identify survival-associated phenotypes for glioblastoma (GBM). This study investigated whether combinations of MRI features can also stratify survival. Furthermore, the molecular differences between phenotype-induced groups were investigated. Ninety-two patients with imaging, molecular, and survival data from the TCGA (The Cancer Genome Atlas)-GBM collection were included in this study. For combinatorial phenotype analysis, hierarchical clustering was used. Groups were defined based on a cutpoint obtained via tree-based partitioning. Furthermore, differential expression analysis of microRNA (miRNA) and mRNA expression data was performed using GenePattern Suite. Functional analysis of the resulting genes and miRNAs was performed using Ingenuity Pathway Analysis. Pathway analysis was performed using Gene Set Enrichment Analysis. Clustering analysis reveals that image-based grouping of the patients is driven by 3 features: volume-class, hemorrhage, and T1/FLAIR-envelope ratio. A combination of these features stratifies survival in a statistically significant manner. A cutpoint analysis yields a significant survival difference in the training set (median survival difference: 12 months, p = 0.004) as well as a validation set (p = 0.0001). Specifically, a low value for any of these 3 features indicates favorable survival characteristics. Differential expression analysis between cutpoint-induced groups suggests that several immune-associated (natural killer cell activity, T-cell lymphocyte differentiation) and metabolism-associated (mitochondrial activity, oxidative phosphorylation) pathways underlie the transition of this phenotype. Integrating data for mRNA and miRNA suggests the roles of several genes regulating proliferation and invasion. A 3-way combination of MRI phenotypes may be capable of stratifying survival in GBM. Examination of molecular processes associated with groups created by this combinatorial phenotype suggests the role of biological processes associated with growth and invasion characteristics.


Prevalence and correlates of drug use and dependence in the United States. Results from the National Comorbidity Survey.
To analyze nationally representative data on the lifetime and 12-month prevalences of use of and dependence on illegal drugs (marijuana/hashish, cocaine/crack, heroin, hallucinogens), nonmedical prescription psychotropic drugs (sedatives, tranquilizers, stimulants, analgesics), and inhalants; and to examine data on the sociodemographic correlates of use and dependence. The data come from the National Comorbidity Survey, a structured diagnostic interview administered to persons aged 15 to 54 years that generates reliable diagnoses according to the definitions and criteria of DSM-III-R. Of the respondents, 51.0% used one of the above drugs at some time in their lives, and 15.4% did so in the past 12 months. These estimates are similar to those obtained in the 1991 National Household Survey of Drug Abuse, where lifetime prevalence was 45.2% and 12-month prevalence was 16.7% among respondents in the age range 15 to 54 years. Of National Comorbidity Survey respondents, 7.5% (14.7% of lifetime users) were dependent at some time in their lives and 1.8% were dependent in the past 12 months. The prevalence estimate for lifetime dependence was reduced to 5.3% when calculated the percentage of respondents in the age range of 28 to 54 years who reported an onset of dependence as of 10 years earlier (ie, when they were 18 to 44 years old) was computed. This is similar to the Epidemiologic Catchment Area Study estimate of 5.1% among respondents in the age range 18 to 44 years, a comparison that matches the two studies on year of assessment, age of risk, and cohort. Males were significantly more likely to report both lifetime and 12-month use and dependence. Use and dependence were found to be more common in cohorts born after World War II than those born before the end of the war. The demographic predictors of lifetime use differed from the predictors of lifetime dependence among users, and these, in turn, differed from the predictors of recent dependence among people with a lifetime history of dependence. Drug use and dependence are highly prevalent in the general population. The fact that there are differences in the correlates of first use, dependence among users, and persistence of dependence means that future research aimed at pinpointing modifiable risk factors must be based on disaggregated analyses of separate stages of progression.


Proton radiosurgery in neurosurgery.
Photon energy deposition from gamma or photon sources follows the law of exponential decay. Consequently, energy is deposited over the entire path of the radiation beam, resulting in dose distribution before and after the target is reached. In contrast, the physical properties of protons are such that energy deposition occurs with no exit dose beyond the target volume. Therefore, relative to photons, proton beams represent a superior platform for the administration of radiosurgery. In this review, the authors will discuss the fundamental principles underlying photon- and proton-based stereotactic radiosurgery (SRS). The clinical efficacy of proton-based SRS in the treatment of arteriovenous malformations, vestibular schwannomas, and pituitary adenomas is reviewed. Direct comparisons of clinical results attained using photon- and proton-based SRS are confounded by a bias toward reserving proton beams for the treatment of larger and more complex lesions. Despite this bias, the clinical outcomes for proton-based SRS have been excellent and have been at least comparable to those for photon-based treatments. The physical properties of proton radiation offer superior conformality in dose distribution relative to photon irradiation. This advantage becomes more apparent as the lesion size increases and will probably be magnified with the development of intensity-modulated proton techniques.


Altered skeletal muscle (mitochondrial) properties in patients with mitochondrial DNA single deletion myopathy.
Mitochondrial myopathy severely affects skeletal muscle structure and function resulting in defective oxidative phosphorylation. However, the major pathomechanisms and therewith effective treatment approaches remain elusive. Therefore, the aim of the present study was to investigate disease-related impairments in skeletal muscle properties in patients with mitochondrial myopathy. Accordingly, skeletal muscle biopsies were obtained from six patients with moleculargenetically diagnosed mitochondrial myopathy (one male and five females, 53 ± 9 years) and eight age- and gender-matched healthy controls (two males and six females, 58 ± 14 years) to determine mitochondrial respiratory capacity of complex I-V, mitochondrial volume density and fiber type distribution. Mitochondrial volume density (4.0 ± 0.5 vs. 5.1 ± 0.8 %) as well as respiratory capacity of complex I-V were lower (P < 0.05) in mitochondrial myopathy and associated with a higher (P < 0.001) proportion of type II fibers (65.2 ± 3.6 vs. 44.3 ± 5.9 %). Additionally, mitochondrial volume density and maximal oxidative phosphorylation capacity correlated positively (P < 0.05) to peak oxygen uptake. Mitochondrial myopathy leads to impaired mitochondrial quantity and quality and a shift towards a more glycolytic skeletal muscle phenotype.


Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: phase II Southwest Oncology Group Study S9504.
To test the concept of taxane sequencing in combined-modality therapy, this phase II trial (S9504) evaluated consolidation docetaxel after concurrent chemoradiotherapy in patients with pathologically documented stage IIIB non-small-cell lung cancer (NSCLC). Results were compared with those of the predecessor study (S9019) with identical eligibility, staging criteria, and treatment, excepting docetaxel consolidation. Treatment consisted of cisplatin 50 mg/m2 on days 1, 8, 29, and 36, etoposide 50 mg/m2 on days 1 through 5 and 29 through 33, and concurrent thoracic radiotherapy (total dose of 61 Gy). Consolidation docetaxel started 4 to 6 weeks after chemoradiotherapy at an initial dose of 75 mg/m2. Stage subsets (tumor-node-metastasis system) in 83 eligible patients were as follows: T4N0/1, 31 patients (37%); T4N2, 22 patients (27%), and T1-3N3, 30 patients (36%). Concurrent chemoradiotherapy was generally well tolerated, but two patients died from probable radiation-associated pneumonitis. Neutropenia during consolidation docetaxel was common (57% with grade 4) and most frequent during escalation to 100 mg/m2. Median progression-free survival was 16 months, median survival was 26 months, and 1-, 2-, and 3-year survival rates were 76%, 54%, and 37%, respectively. Brain metastasis was the most common site of failure. In S9019, median survival was 15 months and 1-, 2-, and 3-year survival rates were 58%, 34%, and 17%, respectively. Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB NSCLC is feasible and generally tolerable, and results compare favorably with the predecessor trial S9019. Nevertheless, this study remains hypothesis-generating and does not provide definitive evidence of the benefit of this approach. Phase III trials evaluating the S9504 regimen have been initiated to validate these results.


Morphological convergence as a consequence of extreme functional demands: examples from the feeding system of natricine snakes.
Despite repeated acquisitions of aquatic or semi-aquatic lifestyles revolving around piscivory, snakes have not evolved suction feeding. Instead, snakes use frontally or laterally directed strikes to capture prey under water. If the aquatic medium constrains strike performance because of its physical properties, we predict morphological and functional convergence in snakes that use similar strike behaviours. Here we use natricine snakes to test for such patterns of convergence in morphology and function. Our data show that frontal strikers have converged on a similar morphology characterized by narrow elongate heads with a reduced projected frontal surface area. Moreover, simple computational fluid dynamics models show that the observed morphological differences are likely biologically relevant as they affect the flow of water around the head. In general, our data suggest that the direction of evolution may be predictable if constraints are strong and evolutionary solutions limited.


Correlations between tumor-infiltrating and circulating lymphocyte subpopulations in advanced renal cancer patients treated with nivolumab.
In clinical trials with immunotherapy, histological features such as tumor-infiltrating lymphocytes (TILs) are investigated as potential predictive biomarkers, with the limit of an outdated parameter for a typically dynamic element. This explorative study compared, in metastatic renal cell carcinoma (mRCC) patients, basal pathological data about TILs on diagnostic histological specimens with circulating lymphocyte subpopulations measured before and during therapy with nivolumab. Of 11 mRCC patients, 5 had low presence of TILs (L-TILs), 3 moderate amount (M-TILs) and 3 high number (H-TILs). Overall, 8 patients had low intratumoral pathological CD4+/CD8+ ratio (LIPR) ≤1 and 3 cases high intratumoral pathological ratio (HIPR) ≥2. Of 8 patients with LIPR, only 2 matched with low circulating CD4+/CD8+ ratio (LCR) ≤1; 5 had high circulating ratio (HCR) ≥2. All 3 cases with HIPR (≥2) conversely had LCR (≤1). Circulating CD4+/CD8+ ratio remained unchanged during therapy (mean -0.12 in 8 weeks). The respective percentage values of CD4+ and CD8+ circulating T cells also remained stable (variation 0%); the absolute value of CD4+ was more likely to increase (mean +46.3/mm3); the level of CD8+ tended to slightly decrease (mean -6.5/mm3). No correlation of lymphocyte subpopulations with treatment outcome was found. Of note, we did not evidence correspondence between histopathological and circulating findings in terms of T-lymphocyte subpopulations, also suggesting the inconsistency of circulating data in terms of relative variations. Considering the likely high dynamism of TILs, rebiopsy before therapy might be proposed to assess the utility of TILs characterization for predictive purpose. (www.actabiomedica.it).


Cyan-white-red luminescence from europium doped Al2O3-La2O3-SiO2 glasses.
Aluminum-lanthanum-silicate glasses with different Eu doping concentration have been synthesized by conventional melt-quenching method at 1680 degrees C in reductive atmosphere. Under 395nm excitation, samples with low Eu doping concentration show mainly the cyan broad emission at 460nm due to 4f(6)5d(1)-4f(7) transition of Eu(2+); and the samples with higher Eu doping concentration show mainly some narrow emissions with maximum at 616nm due to (5)D(0)-(7)F(j) (J=0, 1, 2, 3, 4) transitions of Eu(3+). Cyan-white-red tunable luminescence under 395nm excitation has been obtained by changing the Eu doping concentration.


Ultrasonographic evaluation of portal vein hemodynamics in experimentally bile duct ligated dogs.
The purpose of this study was to evaluate the relationship between the results of laboratory examinations and ultrasonographic findings, especially portal vein hemodynamics in experimentally bile duct ligated dogs. Biliary obstruction was accomplished by surgically occluding the common bile duct in five dogs. All the dogs became visibly jaundiced within 24 hours after surgery. The total protein and albumin/globulin ratio showed a gradual decrease throughout the examination period, while blood urea nitrogen reached its peak in the 6th week and decreased to pre ligation values by the 10th week. Similar trends were noted in the alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and direct and total bilirubin. Total cholesterol and fasting serum bile acid levels rapidly increased after surgery to peak values between the 2nd and 4th week, and then gradually decreased, but still remained high throughout the experiment period. The portal flow volume and velocity significantly (p < 0.05) decreased while only a slight increase was noted in the congestion index after bile duct ligation. The cross sectional area of the portal vein changed insignificantly. Bile duct and gallbladder distention was evident within the 1st week after ligation but there was little change in the echogenicity of the liver parenchyma. The results of this study suggest that the determination of Doppler ultrasound parameters of hepatic hemodynamics, especially the portal vein flow indices, may contribute to a better noninvasive assessment of the canine patient with biliary obstructive disease.


THE CELL JUNCTION IN A LAMELLIBRANCH GILL CILIATED EPITHELIUM : Localization of Pyroantimonate Precipitate.
The junctional complex in the gill epithelium of the freshwater mussel (Elliptio complanatus) consists of an intermediary junction followed by a 2-3 micro long septate junction. Homologous and heterologous cell pairs are connected by this junction. After fixation with 1% OsO(4) containing 1% potassium pyroantimonate, electron microscopy of the gill reveals deposits of electron-opaque precipitate, specifically and consistently localized along cellular membranes. In both junctional and nonjunctional membrane regions, the precipitate usefully outlines the convolutions without obliterating the 150 A intercellular space, which suggests the rarity or absence of either vertebrate-type gap or tight junctions along the entire cell border. The precipitate appears on the cytoplasmic side of the limiting unit membranes of frontal (F), laterofrontal (LF), intermediate (I), lateral (L), and postlateral (PL) cells. The membrane surfaces of certain vesicles of the smooth endoplasmic reticulum, of multivesicular bodies, and of mitochondrial cristae contain precipitate, as does the nucleolus. In other portions of the cell, precipitate is largely absent. The amount of over-all deposition is variable and depends on the treatment of the tissue prior to fixation. Deposition is usually enhanced by pretreatment with 40 mM NaCl as opposed to 40 mM KCl, which suggests that the precipitate is in part sodium pyroantimonate. Treatment with 0.2 mM ouabain does not enhance deposition. Regional differentiation of cell membranes with respect to their ability to precipitate pyroantimonate is found in at least three instances: (a) between the ciliary membranes and other portions of the cell membrane: the precipitate terminates abruptly at the ciliary base, (b) between the LF and I cell borders: the precipitate is asymmetric, favoring the LF side of the junction, and (c) between the septate junctional membrane and adjacent membrane: the precipitate occurs periodically throughout the septate junction region with the periodicity corresponding to the spacing of the septa. This suggests that different regions of the cell membrane may have differing ion permeability properties and, in particular, that the septa may be the regions of high ion permeability in the septate junction.


Opiate receptor down-regulation and desensitization in neuroblastoma X glioma NG108-15 hybrid cells are two separate cellular adaptation processes.
Chronic treatment of neuroblastoma X glioma NG108-15 hybrid cells with the opiate agonist etorphine resulted in a decrease in both opiate receptor density (receptor down-regulation) and opiate ability to inhibit prostaglandin E1 (PGE1)-stimulated increases in cyclic AMP levels (receptor desensitization). Opiate receptor down-regulation and desensitization were homologous as indicated by the lack of apparent change in muscarinic, alpha 2-adrenergic, and PGE1 receptor binding and also retention, albeit modulation, of the ability of carbachol and norepinephrine to inhibit PGE1-stimulated increases in cyclic AMP levels after 24 hr of etorphine treatment. PGE1-stimulated increases in cyclic AMP levels remained identical in etorphine-treated and control cells. Several lines of evidence indicate that receptor desensitization and receptor down-regulation in NG108-15 cells are two separate cellular adaptation processes. (a) With an agonist which appears to be efficiently coupled, i.e., an agonist whose apparent Kd value is much larger than its apparent IC50 value for regulation of cyclic AMP levels (Ki), the concentration of ligand required to produce half-maximal down-regulation is analogous to its Ki value, whereas the concentration of ligand required to produce half-maximal desensitization is related to its Kd value; (b) receptor desensitization precedes receptor down-regulation; (c) only opiate agonists could produce receptor down-regulation, whereas both opiate agonists and partial agonists could desensitize post-receptor occupancy events. Still further evidence for dissociability of these processes was obtained by incubating NG108-15 cells with etorphine at 30 degrees for 2 hr. Under these conditions, there was a decrease in etorphine's ability to regulate adenylate cyclase while [3H]diprenorphine binding remained unaltered. IC50 values of D-Ala2-D-Leu5-enkephalin's competition for [3H]diprenorphine binding to intact cells increased 19.6-fold after etorphine treatment for 90 min, while naloxone IC50 values remained unaltered. This apparent increase in IC50 values was much lower, about 2-fold, when receptor binding was carried out in membranes isolated from cells treated with etorphine chronically. Furthermore, analysis of [3H]etorphine binding to such membranes in the presence of 10 mM Mg2+ indicated a loss of receptor binding sites with no change in apparent affinity, whereas [3H]diprenorphine binding revealed no significant alteration in either Bmax or Kd values. Therefore, during opiate receptor desensitization, a reduction of agonist high-affinity site occurs with no apparent alteration in total receptor number.


When is the burn injury healed?: psychosocial implications of care.
The psychosocial and economic effects of burn trauma are profound, not only for the patients, their families, and the burn unit staff members, but also for society as a whole. Understanding the perception of stresses experienced by patients, families, and staff is discussed, and related strategies to assist in reducing the stress are presented. A comprehensive psychosocial support system can assist the nurse in reducing the psychosocial morbidity of severe burn trauma.


An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain.
ZNF804A, a genomewide supported susceptibility gene for schizophrenia and bipolar disorder, has been associated with task-independent functional connectivity between the left and right dorsolateral prefrontal cortices. Several lines of evidence have converged on the hypothesis that this effect may be mediated by structural connectivity. We tested this hypothesis using diffusion tensor magnetic resonance imaging in three samples: one German sample of 50 healthy individuals, one Scottish sample of 83 healthy individuals and one Scottish sample of 84 unaffected relatives of bipolar patients. Voxel-based analysis and tract-based spatial statistics did not detect any fractional anisotropy (FA) differences between minor allele carriers and individuals homozygous for the major allele at rs1344706. Similarly, region-of-interest analyses and quantitative tractography of the genu of the corpus callosum revealed no significant FA differences between the genotype groups. Examination of effect sizes and confidence intervals indicated that this negative finding is very unlikely to be due to a lack of statistical power. In summary, despite using various analysis techniques in three different samples, our results were strikingly and consistently negative. These data therefore suggest that it is unlikely that the effects of genetic variation at rs1344706 on functional connectivity are mediated by structural integrity differences in large, long-range white matter fiber connections.


Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis.
Chronification of inflammation is the process that lies at the basis of several human diseases that make up to 80% of morbidity and mortality worldwide. It can also explain a great deal of processes related to aging. Atherosclerosis is an example of the most important chronic inflammatory pathology in terms of public health impact. Atherogenesis is based on the inflammatory response of the innate immunity arising locally or focally. The main trigger for this response appears to be modified low-density lipoprotein (LDL), although other factors may also play a role. With the quick resolution of inflammation, atherosclerotic changes in the arterial wall do not occur. However, a violation of the innate immunity response can lead to chronification of local inflammation and, as a result, to atherosclerotic lesion formation. In this review, we discuss possible mechanisms of the impaired immune response with a special focus on mitochondrial dysfunction. Some mitochondrial dysfunctions may be due to mutations in mitochondrial DNA. Several mitochondrial DNA mutations leading to defective mitophagy have been identified. The regulatory role of mitophagy in the immune response has been shown in recent studies. We suggest that defective mitophagy promoted by mutations in mitochondrial DNA can cause innate immunity disorders leading to chronification of inflammation.


Optical inspection of liquid crystal variable retarder inhomogeneities.
Liquid crystal variable retarders (LCVRs) are starting to be widely used in optical systems because of their capacity to provide a controlled variable optical retardance between two orthogonal components of incident polarized light or to introduce a known phase shifting (PS) between coherent waves, both by means of an applied voltage. Typically, the retardance or PS introduced by an LCVR is not homogeneous across the aperture. On the one hand, the LCVR glass substrates present a global bend that causes an overall variation of the retardance or PS. On the other hand, in the manufacturing process of an LCVR, there sometimes appears a set of micro-air bubbles that causes local retardance or PS inhomogeneities. In this work, we present an interferometric technique based on a Mach-Zehnder interferometer that is insensitive to vibrations and capable of inspecting and characterizing the LCVR's retardance or PS inhomogeneities. The feasibility of the proposed method is demonstrated in the experimental results, where the LCVR retardance is measured with an error of about 0.2 rad. The thickness of possible micro-air bubbles is obtained with a resolution of about 50 nm.


Ecological effects of a major oil spill on panamanian coastal marine communities.
In 1986 more than 8 million liters of crude oil spilled into a complex region of mangroves, seagrasses, and coral reefs just east of the Caribbean entrance to the Panama Canal. This was the largest recorded spill into coastal habitats in the tropical Americas. Many population of plants and animals in both oiled and unoiled sites had been studied previously, thereby providing an unprecedented measure of ecological variation before the spill. Documenation of the spread of oil and its biological begun immediately. Intertidal mangroves, algae, and associated invertebrates were covered by oil and died soon after. More surprisingly, there was also extensive mortality of shallow subtidal reef corals and infauna of seagrass beds. After 1.5 years only some organisms in areas exposed to the open sea have recovered.


A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan.
Mutations in the LRRK2 gene are a cause of autosomal dominant Parkinson's disease (PD). Whether LRRK2 variants influence susceptibility to the commoner, sporadic forms of PD remains largely unknown. Data are particularly limited concerning the Asian population. In search for novel, biologically relevant variants, we sequenced the LRRK2 coding region in Taiwanese patients with PD. Four newly identified variants and another variant recently found in a Taiwanese PD family were tested for association with the disease in a sample of 608 PD cases and 373 ethnically matched controls. Heterozygosity for the Gly2385Arg variant was significantly more frequent among PD patients than controls (nominal p value=0.004, corrected for multiple comparisons=0.012, gender- and age-adjusted odds ratio=2.24, 95% C.I.: 1.29-3.88); this variant was uniformly distributed across genders and age strata. Two novel variants, Met1869Val and Glu1874Stop, were found in one PD case each; their pathogenic role remains, therefore, uncertain. The remaining two novel variants (Ala419Val and Pro755Leu) were present with similar frequency in cases and controls, and were therefore, interpreted as disease-unrelated polymorphisms. Our findings suggest that the LRRK2 Gly2385Arg is the first identified, functionally relevant variant, which acts as common risk factor for sporadic PD in the population of Chinese ethnicity.


Identification of electroporation sites in the complex lipid organization of the plasma membrane.
The plasma membrane of a biological cell is a complex assembly of lipids and membrane proteins, which tightly regulate transmembrane transport. When a cell is exposed to strong electric field, the membrane integrity becomes transiently disrupted by formation of transmembrane pores. This phenomenon termed electroporation is already utilized in many rapidly developing applications in medicine including gene therapy, cancer treatment, and treatment of cardiac arrhythmias. However, the molecular mechanisms of electroporation are not yet sufficiently well understood; in particular, it is unclear where exactly pores form in the complex organization of the plasma membrane. In this study, we combine coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis to identify how formation of pores depends on the local lipid organization. We show that pores do not form homogeneously across the membrane, but colocalize with domains that have specific features, the most important being high density of polyunsaturated lipids. We further show that knowing the lipid organization is sufficient to reliably predict poration sites with machine learning. Additionally, by analysing poration kinetics with Bayesian survival analysis we show that poration does not depend solely on local lipid arrangement, but also on membrane mechanical properties and the polarity of the electric field. Finally, we discuss how the combination of atomistic and coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis can guide the design of future experiments and help us to develop an accurate description of plasma membrane electroporation on the whole-cell level. Achieving this will allow us to shift the optimization of electroporation applications from blind trial-and-error approaches to mechanistic-driven design.


Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme.
Using the yeast two-hybrid system, we have identified a human ubiquitin-conjugating enzyme (hE2-25K) as a protein that interacts with the gene product for Huntington disease (HD) (Huntingtin). This protein has complete amino acid identity with the bovine E2-25K protein and has striking similarity to the UBC-1, -4 and -5 enzymes of Saccharomyces cerevisiae. This protein is highly expressed in brain and a slightly larger protein recognized by an anti-E2-25K polyclonal antibody is selectively expressed in brain regions affected in HD. The huntingtin-E2-25K interaction is not obviously modulated by CAG length. We also demonstrate that huntingtin is ubiquitinated. These findings have implications for the regulated catabolism of the gene product for HD.


Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer.
Cancer-associated fibroblasts (CAF) comprise the majority of stromal cells in breast cancers, yet their precise origins and relative functional contributions to malignant progression remain uncertain. Local invasion leads to the proximity of cancer cells and adipocytes, which respond by phenotypical changes to generate fibroblast-like cells termed as adipocyte-derived fibroblasts (ADF) here. These cells exhibit enhanced secretion of fibronectin and collagen I, increased migratory/invasive abilities, and increased expression of the CAF marker FSP-1 but not α-SMA. Generation of the ADF phenotype depends on reactivation of the Wnt/β-catenin pathway in response to Wnt3a secreted by tumor cells. Tumor cells cocultivated with ADFs in two-dimensional or spheroid culture display increased invasive capabilities. In clinical specimens of breast cancer, we confirmed the presence of this new stromal subpopulation. By defining a new stromal cell population, our results offer new opportunities for stroma-targeted therapies in breast cancer.


Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus Species.
A major challenge in developing vaccines for emerging pathogens is their continued evolution and ability to escape human immunity. Therefore, an important goal of vaccine research is to advance vaccine candidates with sufficient breadth to respond to new outbreaks of previously undetected viruses. Ebolavirus (EBOV) vaccines have demonstrated protection against EBOV infection in nonhuman primates (NHP) and show promise in human clinical trials but immune protection occurs only with vaccines whose antigens are matched to the infectious challenge species. A 2007 hemorrhagic fever outbreak in Uganda demonstrated the existence of a new EBOV species, Bundibugyo (BEBOV), that differed from viruses covered by current vaccine candidates by up to 43% in genome sequence. To address the question of whether cross-protective immunity can be generated against this novel species, cynomolgus macaques were immunized with DNA/rAd5 vaccines expressing ZEBOV and SEBOV glycoprotein (GP) prior to lethal challenge with BEBOV. Vaccinated subjects developed robust, antigen-specific humoral and cellular immune responses against the GP from ZEBOV as well as cellular immunity against BEBOV GP, and immunized macaques were uniformly protected against lethal challenge with BEBOV. This report provides the first demonstration of vaccine-induced protective immunity against challenge with a heterologous EBOV species, and shows that Ebola vaccines capable of eliciting potent cellular immunity may provide the best strategy for eliciting cross-protection against newly emerging heterologous EBOV species.


Virological and molecular epidemiological investigations into the role of wild birds in the epidemiology of influenza A/H5N1 in central Thailand.
A serological and virological surveillance program to investigate the HPAI H5N1 virus in wild bird populations was undertaken from February 2007 to October 2008. The purpose of the survey was to investigate the infection status in free ranging wild birds in Banglane district, Nakhon Pathom province, central Thailand. Samples from wild birds were collected every two months. Choanal and cloacal swabs, serum and tissue samples were collected from 421 birds comprising 44 species. Sero-prevalence of the virus tested by H5N1 serum neutralization test (using a H5N1 virus clade 1; A/chicken/Thailand/vsmu-3-BKK/2004) was 2.1% (8 out of 385 samples; 95% CI 0.7, 3.5). Species that were antibody positive included rock pigeons (Columba livia), Asian pied starling (Gracupica contra), spotted dove (Streptopelia chinensis), oriental magpie robin (Copsychus saularis), blue-tailed bee-eater (Merops philippinus), myna (Acridotheres spp.), and pond heron (Ardeola spp.). Prevalence by H5N1 virus isolation was 0.5% (2 out of 421 samples; 95% CI 0.0, 1.1); the two H5N1 virus-positive samples were from Asian pied starling (Gracupica contra) and white vented myna (Acridotheres grandis). Positive virological samples were collected in June 2007 while all positive serology samples were collected between May and August except for one sample collected in December 2007. No positive samples were collected in 2008. Molecular studies revealed that the wild bird H5N1 viruses were closely related to poultry viruses isolated in other parts of Thailand. However, there was no poultry H5N1 prevalence study performed in the study site during the time of this wild bird survey. Interpretation of source of virus isolates would include spill-over of H5N1 viruses from contaminated sources due to movement of domestic poultry and/or fomites from other areas; or infection of wild birds within the outbreak locations and then translocation by wild bird movement and interaction with wild birds inhabiting distant locations.


Skin-pigment regulation of vitamin-D biosynthesis in man.
The known correlation between the color of human skin and latitude (Fig. 2) is explainable in terms of two opposing positive adaptations to solar ultraviolet radiation, weak in northern latitudes in winter yet powerful the year around near the equator. In northern latitudes there is selection for white skins that allow maximum photoactivation of 7-dehydrocholesterol into vitamin D at low intensities of ultraviolet radiation. In southern latitudes, on the other hand, there is selection for black skins able to prevent up to 95 percent of the incident ultraviolet from reaching the deeper layers of the skin where vitamin D is synthesized. Selection against the twin dangers of rickets on the one hand and toxic doses of vitamin D on the other would thus explain the world-wide correlation observed between skin pigmentation and nearness to the equator.


High-performance printable hybrid perovskite solar cells with an easily accessible n-doped fullerene as a cathode interfacial layer.
Engineering the interface between the active layer and the electrodes has proven to be a promising strategy to enhance the power conversion efficiency (PCE) of hybrid perovskite solar cells (PeSCs). Here, we present an effective approach to achieve highly efficient PeSCs by inserting an easy-accessible hexamethonium bromide (HMB)-doped [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) film between the active perovskite layer and the Ag cathode. This doped interfacial layer delivers several remarkable features for use in PeSCs, including solution processability, good electrical conductivity, fine work-function tunability of the Ag electrode, and general applicability to different fullerene materials. As a consequence, planar-heterojunction PeSCs deliver a PCE up to ∼18%, showing an approximately 5.6-fold enhancement compared with the control device using an undoped PC61BM layer. In particular, benefitting from the high conductivity of this doped film, a prominent PCE as high as 15.58% can be achieved even when a large thickness of the PC61BM layer (120 nm) is used. To the best of our knowledge, this is the highest performance ever reported for PeSCs with a PC61BM thickness more than 100 nm. More encouragingly, large-area PeSCs (active area = 1.2 cm2) via the doctor-blade coating technique also exhibit a remarkable PCE (15.23%) and good long-term stability under an inert atmosphere. Our results indicate that the HMB-doped PC61BM film is a promising interfacial layer for PeSCs and can be compatible with high throughput roll-to-roll manufacturing processes.


Community water fluoridation online: an analysis of the digital media ecosystem.
Research demonstrates the safety and efficacy of community water fluoridation (CWF). Yet, the digitization of communication has triggered the spread of inaccurate information online. The purpose of this study was to analyze patterns of CWF information dissemination by a network of sources on the web. We used Media Cloud, a searchable big data platform of over 550 million stories from 50 thousand sources, along with tools to analyze that archive. We generated a network of fluoridation publishers using Media Cloud's keyword identification from August 1, 2015 to July 31, 2016. We defined the media type and sentiment toward CWF for each source and generated a network map of the most influential sources during our study period based on hyperlinking activity. Media Cloud detected a total of 980 stories from 325 different sources related to water fluoridation. We identified nine different media types participating in the dissemination of information: academic, government, scientific group, natural medicine, blogs, mainstream media, advocacy groups, user-generated (e.g., YouTube), and "other." We detected five sub-networks within the overall fluoridation network map, each with its own characteristics. Twenty-one percent of sources were pro-fluoridation, receiving 57 percent of all inlinks, 22 percent of sources were anti-fluoridation, and the rest were neutral (54 percent). The dominant neutral sentiment of the network may signify that anti- and pro-sides of the debate are viewed as balanced, not just in number but also in quality of information. Despite high inlinks to pro-sources, anti-fluoridation sentiment maintains influence online.


Decreasing Time to Initiation of Chemotherapy for Patients Electively Admitted to a Hematologic Malignancy Service.
Delays in initiating elective inpatient chemotherapy can decrease patient satisfaction and increase length of stay. At our institution, we observed that 86% of patients who were admitted for elective chemotherapy experienced a delay-more than 6 hours-with a median time to chemotherapy of 18.9 hours. We developed a process improvement initiative to improve time to chemotherapy for elective chemotherapy admissions. Our outcome measure was the time from admission to chemotherapy administration in patients who were admitted for elective chemotherapy. Process measures were identified and monitored. We collected baseline data and used performance improvement tools to identify key drivers. We focused on these key drivers to develop multiple plan-do-study-act cycles to improve our outcome measure. Once we started an intervention, we collected data every 2 weeks to assess our intervention. At the time of interim analysis, we observed a median decrease in time to chemotherapy administration from 18.9 hours to 8.85 hours (P = .005). Median time to laboratory results resulted decreased from 3.17 hours to 0.00 hours. There was no change in time from signing chemotherapy to nurse releasing the chemotherapy. We noted that more providers were signing the chemotherapy before patient admission. By implementing new admission workflows, optimizing our use of the electronic medical record to communicate among providers, and improving preadmission planning we were able to reduce our median time to chemotherapy for elective admissions by 53.2%. Improvement is still needed to meet our goals and to ensure the sustainability of these ongoing efforts.


Phosphorylation of human hnRNP protein A1 abrogates in vitro strand annealing activity.
In HeLa cells metabolically labeled in vivo with [32P] orthophosphate in the presence of okadaic acid the concentration of phosphorylated A1 protein was increased significantly as compared to controls. Purified recombinant hnRNP protein A1 served as an excellent substrate in vitro for the catalytic subunit of cAMP-dependent protein kinase (PKA) and for casein kinase II (CKII). Thin layer electrophoresis of A1 acid hydrolysates showed the protein to be phosphorylated exclusively on serine residue by both kinases. V8 phosphopeptide maps revealed that the target site(s) of in vitro phosphorylation are located in the C-terminal region of A1. Phosphoamino acid sequence analysis and site directed mutagenesis identified Ser 199 as the sole phosphoamino acid in the protein phosphorylated by PKA. Phosphorylation introduced by PKA resulted in the suppression of the ability of protein A1 to promote strand annealing in vitro, without any detectable effect on its nucleic acid binding capacity. This finding indicates that phosphorylation of a single serine residue in the C-terminal domain may significantly alter the properties of protein A1.


Using Pneumococcal Carriage Data to Monitor Postvaccination Changes in the Incidence of Pneumococcal Otitis Media.
Pneumococcal conjugate vaccines (PCVs) have substantially reduced the burden of pneumococcal disease, including the incidence of otitis media (OM). However, in most countries, no surveillance exists to monitor the change in pneumococcal OM incidence after the introduction of PCVs. We explored whether measuring pneumococcal carriage was a useful surrogate for monitoring postvaccination changes in the incidence of pneumococcal OM. The 7-valent PCV was introduced to Israel's national immunization program in July 2009 and gradually replaced by the 13-valent PCV starting in November 2010. Each day since 2009, nasopharyngeal swabs have been obtained from the first 4 Bedouin children and the first 4 Jewish children who were younger than 5 years old and attended a pediatric emergency room in southern Israel. During the same time, OM surveillance in southern Israel included all children younger than 2 years of age who were diagnosed with OM and had undergone a middle-ear fluid culture. The relative change in the prevalence of vaccine-serotype (VT) pneumococcal carriage was predictive of the relative change in incidence of OM due to VT pneumococcus. However, the serotype replacement observed in non-VT carriage is not paralleled in the incidence of OM due to non-VT pneumococcus. This could indicate that there are more complex mechanisms of the immune response involved in preventing initial and consecutive episodes of OM, which has been changed through declining prevalence of the most virulent serotypes as a result of vaccination.


Surface phenotype and functionality of WNV specific T cells differ with age and disease severity.
West Nile virus (WNV) infection can result in severe neuroinvasive disease, particularly in persons with advanced age. As rodent models demonstrate that T cells play an important role in limiting WNV infection, and strong T cell responses to WNV have been observed in humans, we postulated that inadequate antiviral T cell immunity was involved in neurologic sequelae and the more severe outcomes associated with age. We previously reported the discovery of six HLA-A*0201 restricted WNV peptide epitopes, with the dominant T cell targets in naturally infected individuals being SVG9 (Env) and SLF9 (NS4b). Here, memory phenotype and polyfunctional CD8+ T cell responses to these dominant epitopes were assessed in 40 WNV seropositive patients displaying diverse clinical symptoms. The patients' PBMC were stained with HLA-I multimers loaded with the SVG9 and SLF9 epitopes and analyzed by multicolor flow cytometry. WNV-specific CD8+ T cells were found in peripheral blood several months post infection. The number of WNV-specific T cells in older individuals was the same, if not greater, than in younger members of the cohort. WNV-specific T cells were predominantly monofunctional for CD107a, MIP-1β, TNFα, IL-2, or IFNγ. When CD8+ T cell responses were stratified by disease severity, an increased number of terminally differentiated, memory phenotype (CD45RA+ CD27- CCR7- CD57+) T cells were detected in patients suffering from viral neuroinvasion. In conclusion, T cells of a terminally differentiated/cytolytic profile are associated with neuroinvasion and, regardless of age, monofunctional T cells persist following infection. These data provide the first indication that particular CD8+ T cell phenotypes are associated with disease outcome following WNV infection.


Dicarbonylative benzannulation of 3-acetoxy-1,4-enynes with CO and silylboranes by Pd and Cu cooperative catalysis: one-step access to 3-hydroxyarylacylsilanes.
A new, general Pd/Cu-cocatalysed dicarbonylative benzannulation of 3-acetoxy-1,4-enynes with CO and silylboranes is described. The method utilizes CO as both a one-carbon (C1) unit and an external addition functional reagent to achieve an unprecedented dicarbonylative benzannulation process, and represents a facile, efficient route to 3-hydroxyarylacylsilanes. Mechanistically, the silyl-Cu intermediate formed from CuF2 and silylboranes, and silyl-Pd intermediate generated by transmetallation are two key factors for successfully targeting the reaction and selectivity.


[New argentine consensus of respiratory rehabilitation 2008].
Respiratory rehabilitation (RR) is a multidisciplinary program of care for patients with chronic respiratory impairment, individually tailored, designed to optimize physical and social performance and patient autonomy. It is particularly indicated in chronic obstructive pulmonary disease (COPD) patients with exercise intolerance. The objectives of respiratory rehabilitation are: reduction in symptoms and exercise intolerance, improvement of health-related quality of life, and reduction of health costs. A group of neumonologists, nutritionists and physical therapists performed a systematic review of the evidence in RR to update previous local guidelines. Inclusion and exclusion criteria, guidelines for initial evaluation and follow up and resources needed are defined. Training characteristics are recommended regarding frequency of the visits, intensity, progression and duration of the exercise training. Aerobic training was recommended for lower limb (1A), upper limb (1B). Strength training must be added (1B). Respiratory muscle training and other physiotherapy techniques were recommended only for specific patients (1C). In addition recommendations have been made for educational objectives of the program including smoking cessation, nutritional and psychological support. The positive impact of RR on reductions of health care costs and reductions on hospitalizations (Evidence A) and mortality (Evidence B) were analized. Respiratory rehabilitation is a key component in the modern treatment of COPD patients. This consensus statement was prepared based on the most recent scientific evidence and adjusted to the local environment with the aim of being implemented nationally.


Establishment of a rapid and footprint-free protocol for differentiation of human embryonic stem cells into pancreatic endocrine cells with synthetic mRNAs encoding transcription factors.
Transplantation of pancreatic β cells generated in vitro from pluripotent stem cells (hPSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) has been proposed as an alternative therapy for diabetes. Though many differentiation protocols have been developed for this purpose, lentivirus-mediated forced expression of transcription factors (TF)-PDX1 and NKX6.1-has been at the forefront for its relatively fast and straightforward approach. However, considering that such cells will be used for therapeutic purposes in the future, it is desirable to develop a procedure that does not leave any footprint on the genome, as any changes of DNAs could potentially be a source of unintended, concerning effects such as tumorigenicity. In this study, we attempted to establish a novel protocol for rapid and footprint-free hESC differentiation into a pancreatic endocrine lineage by using synthetic mRNAs (synRNAs) encoding PDX1 and NKX6.1. We also tested whether siPOU5F1, which reduces the expression of pluripotency gene POU5F1 (also known as OCT4), can enhance differentiation as reported previously for mesoderm and endoderm lineages. synRNA-PDX1 and synRNA-NKX6.1 were synthesized in vitro and were transfected five times to hESCs with a lipofection reagent in a modified differentiation culture condition. siPOU5F1 was included only in the first transfection. Subsequently, cells were seeded onto a low attachment plate and aggregated by an orbital shaker. At day 13, the degree of differentiation was assessed by quantitative RT-PCR (qRT-PCR) and immunohistochemistry for endocrine hormones such as insulin, glucagon, and somatostatin. Both PDX1 and NKX6.1 expression were detected in cells co-transfected with synRNA-PDX1 and synRNA-NKX6.1 at day 3. Expression levels of insulin in the transfected cells at day 13 were 450 times and 14 times higher by qRT-PCR compared to the levels at day 0 and in cells cultured without synRNA transfection, respectively. Immunohistochemically, pancreatic endocrine hormones were not detected in cells cultured without synRNA transfection but were highly expressed in cells transfected with synRNA-PDX1, synRNA-NKX6.1, and siPOU5F1 at as early as day 13. In this study, we report a novel protocol for rapid and footprint-free differentiation of hESCs to endocrine cells.


Preventing surgical site infections after bariatric surgery: value of perioperative antibiotic regimens.
Bariatric surgery for obesity has emerged as an effective and commonly used treatment modality. This paper reviews the surgical site infections (SSIs) that occur post bariatric surgery and SSI prevention. The benefit of bariatric surgery resulting in profound weight loss brings with it consequences in the form of postoperative complications that can have profound effects on morbidity and mortality in these patients. This paper sets out to define different types of SSIs that occur following bariatric surgery and to discuss existing literature on the critical aspects of SSI prevention and the appropriate use of surgical antimicrobial prophylaxis for bariatric surgery.


Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection.
Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ~2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (~six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.


Evolutionary Dynamics of the Cellulose Synthase Gene Superfamily in Grasses.
Phylogenetic analyses of cellulose synthase (CesA) and cellulose synthase-like (Csl) families from the cellulose synthase gene superfamily were used to reconstruct their evolutionary origins and selection histories. Counterintuitively, genes encoding primary cell wall CesAs have undergone extensive expansion and diversification following an ancestral duplication from a secondary cell wall-associated CesA. Selection pressure across entire CesA and Csl clades appears to be low, but this conceals considerable variation within individual clades. Genes in the CslF clade are of particular interest because some mediate the synthesis of (1,3;1,4)-β-glucan, a polysaccharide characteristic of the evolutionarily successful grasses that is not widely distributed elsewhere in the plant kingdom. The phylogeny suggests that duplication of either CslF6 and/or CslF7 produced the ancestor of a highly conserved cluster of CslF genes that remain located in syntenic regions of all the grass genomes examined. A CslF6-specific insert encoding approximately 55 amino acid residues has subsequently been incorporated into the gene, or possibly lost from other CslFs, and the CslF7 clade has undergone a significant long-term shift in selection pressure. Homology modeling and molecular dynamics of the CslF6 protein were used to define the three-dimensional dispositions of individual amino acids that are subject to strong ongoing selection, together with the position of the conserved 55-amino acid insert that is known to influence the amounts and fine structures of (1,3;1,4)-β-glucans synthesized. These wall polysaccharides are attracting renewed interest because of their central roles as sources of dietary fiber in human health and for the generation of renewable liquid biofuels.


Activation of Brainstem Pro-opiomelanocortin Neurons Produces Opioidergic Analgesia, Bradycardia and Bradypnoea.
Opioids are widely used medicinally as analgesics and abused for hedonic effects, actions that are each complicated by substantial risks such as cardiorespiratory depression. These drugs mimic peptides such as β-endorphin, which has a key role in endogenous analgesia. The β-endorphin in the central nervous system originates from pro-opiomelanocortin (POMC) neurons in the arcuate nucleus and nucleus of the solitary tract (NTS). Relatively little is known about the NTSPOMC neurons but their position within the sensory nucleus of the vagus led us to test the hypothesis that they play a role in modulation of cardiorespiratory and nociceptive control. The NTSPOMC neurons were targeted using viral vectors in a POMC-Cre mouse line to express either opto-genetic (channelrhodopsin-2) or chemo-genetic (Pharmacologically Selective Actuator Modules). Opto-genetic activation of the NTSPOMC neurons in the working heart brainstem preparation (n = 21) evoked a reliable, titratable and time-locked respiratory inhibition (120% increase in inter-breath interval) with a bradycardia (125±26 beats per minute) and augmented respiratory sinus arrhythmia (58% increase). Chemo-genetic activation of NTSPOMC neurons in vivo was anti-nociceptive in the tail flick assay (latency increased by 126±65%, p<0.001; n = 8). All effects of NTSPOMC activation were blocked by systemic naloxone (opioid antagonist) but not by SHU9119 (melanocortin receptor antagonist). The NTSPOMC neurons were found to project to key brainstem structures involved in cardiorespiratory control (nucleus ambiguus and ventral respiratory group) and endogenous analgesia (periaqueductal gray and midline raphe). Thus the NTSPOMC neurons may be capable of tuning behaviour by an opioidergic modulation of nociceptive, respiratory and cardiac control.


Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria.
We have shown previously that peripheral lymph node-resident retinoic acid receptor-related orphan receptor γt(+) NK1.1(-) invariant NKT (iNKT) cells produce IL-17A independently of IL-6. In this study, we show that the concomitant presence of IL-1 and IL-23 is crucial to induce a rapid and sustained IL-17A/F and IL-22 response by these cells that requires TCR-CD1d interaction and partly relies on IL-23-mediated upregulation of IL-23R and IL-1R1 expression. We further show that IL-1 and IL-23 produced by pathogen-associated molecular pattern-stimulated dendritic cells induce this response from NK1.1(-) iNKT cells in vitro, involving mainly TLR2/4-signaling pathways. Finally, we found that IL-17A production by these cells occurs very early and transiently in vivo in response to heat-killed bacteria. Overall, our study indicates that peripheral lymph node NK1.1(-) iNKT cells could be a source of innate Th17-related cytokines during bacterial infections and supports the hypothesis that they are able to provide an efficient first line of defense against bacterial invasion.


The psychology of elite cycling: a systematic review.
This systematic review sought to synthesise what is currently known about the psychology of elite cycling. Nine electronic databases were searched in March 2017 for studies reporting an empirical test of any psychological construct in an elite cycling sample. Fourteen studies (total n = 427) met inclusion criteria. Eight studies were coded as having high risk of bias. Themes extracted included mood, anxiety, self-confidence, pain, and cognitive function. Few studies had similar objectives meaning that in many instances findings could not be synthesised in a meaningful way. Nevertheless, there was some cross-study evidence that elite cyclists have more positive mood states (relative to normative scores), pre-race anxiety impairs performance (among male cyclists), and associative strategies are perceived as helpful for pain management. Among single studies coded as having low risk of bias, evidence suggests that implicit beliefs affect decision making performance, elite cyclists are less susceptible to mental fatigue (than non-elite cyclists), and better leadership skills relates to greater social labouring. Limitations include non-standardisation of measures, lack of follow-up data, small sample sizes, and overall poor research quality. The findings of this systematic review might be used to inform research and theory development on the psychology of elite endurance cycling.


Our Cosmic Insignificance.
The universe that surrounds us is vast, and we are so very small. When we reflect on the vastness of the universe, our humdrum cosmic location, and the inevitable future demise of humanity, our lives can seem utterly insignificant. Many philosophers assume that such worries about our significance reflect a banal metaethical confusion. They dismiss the very idea of cosmic significance. This, I argue, is a mistake. Worries about cosmic insignificance do not express metaethical worries about objectivity or nihilism, and we can make good sense of the idea of cosmic significance and its absence. It is also possible to explain why the vastness of the universe can make us feel insignificant. This impression does turn out to be mistaken, but not for the reasons typically assumed. In fact, we might be of immense cosmic significance-though we cannot, at this point, tell whether this is the case.


Correlation of subjective questionnaires with cardiac function as determined by exercise testing in a pediatric population.
Although exercise testing is an important objective method used to assess cardiopulmonary function, subjective assessment often is used as a proxy in the clinical setting. This study aimed to determine whether responses to a subjective functional capacity questionnaire administered to parents and patients in a pediatric exercise laboratory correlate with objective assessment of functional capacity, measured by peak oxygen consumption during maximal voluntary exercise testing. Subjective questionnaire responses and exercise test results collected over 10 years were retrospectively analyzed. Symptoms and physical capabilities were assessed using a 6-point Likert scale regarding the ability to attend school/work, walk, climb stairs, and run, as well as the frequency of fatigue, palpitations, and chest pain. Values of 0 to 3 were considered abnormal, whereas values of 4-5 were regarded as normal. Exercise testing was performed on a stationary cycle ergometer with a continuous ramping protocol. Heart rate and oxygen saturation were continuously monitored. Blood pressures and electrocardiograms (ECGs) were obtained at 2-min intervals. Metabolic gas analysis was performed using a breath-by-breath method. The results of the exercise testing were normalized for body size and expressed as a percentage of predicted peak oxygen consumption (%pVO(2)). Very weak but statistically significant correlations (τ < 0.25; P < 0.05) between the scores of the school/work, walking, stair climbing, running, and fatigue items and %pVO(2) were found using Kendall's rank correlations. The subjective Likert scales used to assess basic physical capacity and cardiac-associated symptoms have limited ability to predict actual functional capacity as measured by %pVO(2) achieved. The very weak rank-order correlation between %pVO(2) achieved and the subjective reporting of the ability to attend school/work, walk, climb stairs, and run has low clinical significance and will not be useful in predicting functional capacity within the clinic setting.