The sudden collapse of pollinator communities.
Declines in pollinator populations may harm biodiversity and agricultural productivity. Little attention has, however, been paid to the systemic response of mutualistic communities to global environmental change. Using a modelling approach and merging network theory with theory on critical transitions, we show that the scale and nature of critical transitions is likely to be influenced by the architecture of mutualistic networks. Specifically, we show that pollinator populations may collapse suddenly once drivers of pollinator decline reach a critical point. A high connectance and/or nestedness of the mutualistic network increases the capacity of pollinator populations to persist under harsh conditions. However, once a tipping point is reached, pollinator populations collapse simultaneously. Recovering from this single community-wide collapse requires a relatively large improvement of conditions. These findings may have large implications for our view on the sustainability of pollinator communities and the services they provide.


2000 CDC Growth Charts for the United States: methods and development.
This report provides detailed information on how the 2000 Centers for Disease Control and Prevention (CDC) growth charts for the United States were developed, expanding upon the report that accompanied the initial release of the charts in 2000. The growth charts were developed with data from five national health examination surveys and limited supplemental data. Smoothed percentile curves were developed in two stages. In the first stage, selected empirical percentiles were smoothed with a variety of parametric and nonparametric procedures. In the second stage, parameters were created to obtain the final curves, additional percentiles and z-scores. The revised charts were evaluated using statistical and graphical measures. The 1977 National Center for Health Statistics (NCHS) growth charts were revised for infants (birth to 36 months) and older children (2 to 20 years). New body mass index-for-age (BMI-for-age) charts were created. Use of national data improved the transition from the infant charts to those for older children. The evaluation of the charts found no large or systematic differences between the smoothed percentiles and the empirical data. The 2000 CDC growth charts were developed with improved data and statistical procedures. Health care providers now have an instrument for growth screening that better represents the racial-ethnic diversity and combination of breast- and formula-feeding in the United States. It is recommended that these charts replace the 1977 NCHS charts when assessing the size and growth patterns of infants, children, and adolescents.


Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse.
EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES. We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively. Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases. Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse.


Fitting methods to paradigms: are ergonomics methods fit for systems thinking?
The issues being tackled within ergonomics problem spaces are shifting. Although existing paradigms appear relevant for modern day systems, it is worth questioning whether our methods are. This paper asks whether the complexities of systems thinking, a currently ubiquitous ergonomics paradigm, are outpacing the capabilities of our methodological toolkit. This is achieved through examining the contemporary ergonomics problem space and the extent to which ergonomics methods can meet the challenges posed. Specifically, five key areas within the ergonomics paradigm of systems thinking are focused on: normal performance as a cause of accidents, accident prediction, system migration, systems concepts and ergonomics in design. The methods available for pursuing each line of inquiry are discussed, along with their ability to respond to key requirements. In doing so, a series of new methodological requirements and capabilities are identified. It is argued that further methodological development is required to provide researchers and practitioners with appropriate tools to explore both contemporary and future problems. Practitioner Summary: Ergonomics methods are the cornerstone of our discipline. This paper examines whether our current methodological toolkit is fit for purpose given the changing nature of ergonomics problems. The findings provide key research and practice requirements for methodological development.


Controlling invasive rodents via synthetic gene drive and the role of polyandry.
House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male's sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three- to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.


Importance of genetic effects for characteristics of the human iris.
The relative importance of genetic influences (heritability) on five general textural quality characteristics of the human iris was assessed using sex and age limitation models. Colour photographs of irises were available from 100 monozygotic twin pairs, 99 dizygotic twin pairs, and 99 unrelated randomly paired age-matched German subjects. Comparative scales were constructed and two judges who were blind to zygosity independently rated five characteristic of the subjects' left iris. Inter-rater reliabilities were larger than.90 for all five scales. The heritabilities for the five iris characteristics ranged from.51-.90. No sex-specific genetic factors were found for the iris characteristics. Age-group differences in heritability were found for one of the five iris characteristics - "distinction of white dot rings". Heritability was greater for the older cohort (90%) than the younger (73%). The iris characteristics that showed the next highest additive-genetic effect were "contractional furrows" (78%) and "frequency of crypts" in the main stroma leaf (66%).


Painleve' analysis of a variable coefficient Sine-Gordon equation.
In this paper we study a variable coefficient Sine-Gordon (vSG) equation given by theta(tt)-theta(xx)+F(x,t)sin theta=0 where F(x,t) is a real function. To establish if it may be integrable we have performed the standard test of Weiss, Tabor, and Carnevale (WTC). We have got that the (vSG) equation has the Painleve' property (Pp) if the function F(x,t) satisfies a well-defined nonlinear partial differential equation. We have found the general solution of this last equation and, consequently, the functions F(x,t) such that the (vSG) equation possesses the (Pp), are given by F(x,t)=F(1)(x+t)F(2)(x-t) where F(1)(x+t) and F(2)(x-t) are arbitrary functions. Using this last result we have obtained some particular solutions of the vSG equation. (c) 1995 American Institute of Physics.


The food and environmental safety of Bt crops.
Bacillus thuringiensis (Bt) microbial pesticides have a 50-year history of safety in agriculture. Cry proteins are among the active insecticidal ingredients in these pesticides, and genes coding for Cry proteins have been introduced into agricultural crops using modern biotechnology. The Cry gene sequences are often modified to enable effective expression in planta and several Cry proteins have been modified to increase biological activity against the target pest(s). Additionally, the domains of different but structurally conserved Cry proteins can be combined to produce chimeric proteins with enhanced insecticidal properties. Environmental studies are performed and include invertebrates, mammals, and avian species. Mammalian studies used to support the food and feed safety assessment are also used to support the wild mammal assessment. In addition to the NTO assessment, the environmental assessment includes a comparative assessment between the Bt crop and the appropriate conventional control that is genetically similar but lacks the introduced trait to address unintended effects. Specific phenotypic, agronomic, and ecological characteristics are measured in the Bt crop and the conventional control to evaluate whether the introduction of the insect resistance has resulted in any changes that might cause ecological harm in terms of altered weed characteristics, susceptibility to pests, or adverse environmental impact. Additionally, environmental interaction data are collected in field experiments for Bt crop to evaluate potential adverse effects. Further to the agronomic and phenotypic evaluation, potential movement of transgenes from a genetically modified crop plants into wild relatives is assessed for a new pest resistance gene in a new crop. This review summarizes the evidence for safety of crops containing Cry proteins for humans, livestock, and other non-target organisms.


Genome-wide analysis of genes related to ovary activation in worker honey bees.
A defining characteristic of eusocial animals is their division of labour into reproductive and nonreproductive specialists. Here, we used a microarray study to identify genes associated with functional sterility in the worker honey bee Apis mellifera. We contrasted gene expression in workers from a functionally sterile wild-type strain with that in a mutant (anarchist) strain selected for high rates of ovary activation. We identified a small set of genes from the brain (n = 7) and from the abdomen (n = 5) that are correlated in their expression with early stages of ovary activation. Sterile wild-type workers up-regulated two unknown genes and a homologue of Drosophila CG6004. By contrast, reproductive anarchist workers up-regulated genes for the yolk protein vitellogenin, venom peptides and a member of the AdoHycase superfamily, among others. The differentially expressed genes identified are likely to be involved in early differentiation into sterile and reproductive worker phenotypes and may therefore form part of the gene networks associated with the regulation of honey bee worker sterility. Our study may have lacked sufficient power to detect all but a minority of biologically relevant changes taking place; however, the differential expression of vitellogenin and a putative AdoHycase suggests that our screen has captured core reproductive genes and that ovary activation may involve an epigenetic mechanism.


Blood pressure variability and the development of early neurological deterioration following acute ischemic stroke.
Early neurological deterioration (END) is a common condition associated with poor outcome after acute ischemic stroke. We studied association between blood pressure (BP) variability and development of END. In this retrospective observational study, we studied a consecutive series of patients hospitalized for acute ischemic stroke within 24 h of onset. The primary outcome of interest was the development of END according to predefined criteria within the first 72 h of stroke onset. During this period, the mean, maximum (max), and minimum (min) values for the SBP and DBP were measured. The following parameters of BP variability were calculated for the SBP and DBP: the difference between the maximum and minimum (max-min), the SD, and the coefficient of variation. Of the 1161 patients enrolled in the study (mean age, 67.5 ± 13.3 years; 59.6% men), 210 (18.1%) developed END. All of the BP variability parameters were linearly associated with END independent of mean BP and potential clinical variables (P values < 0.05 on likelihood ratio tests for trend), except for SBPmax-min. Among the other BP parameters, SBPmean, SBPmax, DBPmax, and DBPmin were independently associated with END. After adjustments for potential confounders, the odds for END increased 14-21% with each increase of one standard deviation in the BP variability parameter. BP variability is independently and linearly associated with the development of neurologic deterioration in acute stage of ischemic stroke.


An efficient two-phase L(1)-TV method for restoring blurred images with impulse noise.
A two-phase image restoration method based upon total variation regularization combined with an L(1)-data-fitting term for impulse noise removal and deblurring is proposed. In the first phase, suitable noise detectors are used for identifying image pixels contaminated by noise. Then, in the second phase, based upon the information on the location of noise-free pixels, images are deblurred and denoised simultaneously. For efficiency reasons, in the second phase a superlinearly convergent algorithm based upon Fenchel-duality and inexact semismooth Newton techniques is utilized for solving the associated variational problem. Numerical results prove the new method to be a significantly advance over several state-of-the-art techniques with respect to restoration capability and computational efficiency.


Detection of Small Changes in Psoriasis Intensity with PrecisePASI.
The Psoriasis Area and Severity Index (PASI) is the score of choice to grade psoriasis severity and detect clinical changes. Due to low resolution based on the calculation of the score by fixed area classes, PASI scores <10 have little value. At 756 patient examinations, psoriasis activity was measured with both PASI and PrecisePASI. PrecisePASI has a linear increase while PASI has a staircase pattern. Both scores meet at the endpoint-relevant values of body surface area (BSA) 10, 30, 50, 70 and 90%. PASI and PrecisePASI correlate significantly over the whole range of BSA. In the region of BSA <5%, PrecisePASI shows a significantly higher resolution (p < 0.0001). The calculation of PrecisePASI corrects the undesired inaccuracies of PASI in the lower BSA ranges and is a tool to use as an endpoint in trials aiming to detect differences in the lower ranges of BSA.


Anticoagulation and atrial fibrillation.
The decision to anticoagulate patients with atrial fibrillation (AF) involves weighting the risk of an embolic event without therapy versus the risk of a hemorrhagic event on therapy. Improved methods of monitoring anticoagulation with the International Normalized Ratio (INR), and recent evidence of the efficacy and safety of low-dose warfarin (INR range 2.0 to 3.0) have clarified the role of anticoagulation in AF. Over the past four years, five large prospective randomized trials in patients with nonvalvular atrial fibrillation (NVAF) have reported substantial reductions in stroke in patients treated with low-dose warfarin therapy. The results of these trials, combined with previous studies, suggest that anticoagulation is the treatment of choice for patients with atrial fibrillation associated with rheumatic valvular disease, prosthetic valve disease, and now NVAF. Although the results of the prospective atrial fibrillation trials are very consistent in regard to the efficacy and safety of anticoagulation, there continues to be uncertainty regarding which subgroups of patients are at highest risk for embolic events. Subgroups that appear to be at high risk include patients with hypertension, previous embolic events, structural heart disease (enlarged left atrial size, previous myocardial infarction, left ventricular dysfunction), and older age. Young patients with no evidence of structural heart disease or hypertension (lone atrial fibrillation) have a low embolic rate and do not warrant anticoagulation. Recent studies suggest that there is little difference in the risk of stroke in patients with paroxysmal or chronic AF, therefore this factor should not have a major impact on therapeutic decisions. Anticoagulation is also recommended for patients undergoing elective cardioversion (recent onset of atrial fibrillation greater than two days in duration), and patients with atrial fibrillation and hyperthyroidism because of studies suggesting a higher rate of embolism if these patients are not anticoagulated. The role of aspirin in AF is less clear as only two of the five prospective trials randomized patients to aspirin therapy and only one documented aspirin benefit. Therefore, aspirin appears to offer less benefit but is a satisfactory alternative to warfarin therapy. Aspirin is currently recommend for patients who are poor candidates for anticoagulation or individuals with AF who are considered to be at low risk for stroke.


Malposition of feeding tubes in neonates: is it an issue?
Accurate tube placement of orogastric and nasogastric feeding tubes in neonates is important to ensure safe and effective enteral feeding. Errors in placement and position of feeding tubes are described in literature, but there is little evidence of the exact prevalence of improperly placed tubes, especially in neonates. To evaluate the prevalence of improperly placed feeding tubes, we reviewed 381 consecutive radiographs and defined the position of the feeding tubes. We found that in 41% of the placements, the optimal position of the feeding tubes was achieved, whereas overall 59% of the feeding tubes had been placed incorrectly. There is a need for both better rules to measure the distance between nose (lips) and the body of the stomach and improved methods to confirm correct tube position in neonates.


Trajectory-based differential expression analysis for single-cell sequencing data.
Trajectory inference has radically enhanced single-cell RNA-seq research by enabling the study of dynamic changes in gene expression. Downstream of trajectory inference, it is vital to discover genes that are (i) associated with the lineages in the trajectory, or (ii) differentially expressed between lineages, to illuminate the underlying biological processes. Current data analysis procedures, however, either fail to exploit the continuous resolution provided by trajectory inference, or fail to pinpoint the exact types of differential expression. We introduce tradeSeq, a powerful generalized additive model framework based on the negative binomial distribution that allows flexible inference of both within-lineage and between-lineage differential expression. By incorporating observation-level weights, the model additionally allows to account for zero inflation. We evaluate the method on simulated datasets and on real datasets from droplet-based and full-length protocols, and show that it yields biological insights through a clear interpretation of the data.


NS5A Gene Analysis by Next Generation Sequencing in HCV Nosocomial Transmission Clusters of HCV Genotype 1b Infected Patients.
Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with β-thalassemia]. Resistance-associated-substitutions (RAS) were analysed by Geno2pheno-algorithm. Nucleotide-sequence-variability (NSV, at 1%, 2%, 5%, 10% and 15% NGS-cutoffs) and Shannon entropy were estimated. Phylogenetic analysis was performed by Mega6-software and Bayesian-analysis. Results: Phylogenetic analysis showed five transmission-clusters: one involving four HCV-acute onco-hematologic-patients; one involving three HCV-chronic β-thalassemia-patients and three involving both HCV-acute and chronic β-thalassemia-patients. The NS5A-RAS Y93H was found in seven patients, distributed differently among chronic/acute patients involved in the same transmission-clusters, independently from the host-genetic IL-28-polymorphism. The intra-host NSV was higher in chronic-patients versus acute-patients, at all cutoffs analyzed (p < 0.05). Even though Shannon-entropy was higher in chronic-patients, significantly higher values were observed only in chronic β-thalassemia-patients versus acute β-thalassemia-patients (p = 0.01). Conclusions: In nosocomial HCV transmission-clusters, the intra-host HCV quasispecies divergence in patients with acute-infection was very low in comparison to that in chronic-infection. The NS5A-RAS Y93H was often transmitted and distributed differently within the same transmission-clusters, independently from the IL-28-polymorphism.


BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants.
To conduct a systematic review and meta-analysis of cohort studies of body mass index (BMI) and the risk of all cause mortality, and to clarify the shape and the nadir of the dose-response curve, and the influence on the results of confounding from smoking, weight loss associated with disease, and preclinical disease. PubMed and Embase databases searched up to 23 September 2015. Cohort studies that reported adjusted risk estimates for at least three categories of BMI in relation to all cause mortality. Summary relative risks were calculated with random effects models. Non-linear associations were explored with fractional polynomial models. 230 cohort studies (207 publications) were included. The analysis of never smokers included 53 cohort studies (44 risk estimates) with >738 144 deaths and >9 976 077 participants. The analysis of all participants included 228 cohort studies (198 risk estimates) with >3 744 722 deaths among 30 233 329 participants. The summary relative risk for a 5 unit increment in BMI was 1.18 (95% confidence interval 1.15 to 1.21; I(2)=95%, n=44) among never smokers, 1.21 (1.18 to 1.25; I(2)=93%, n=25) among healthy never smokers, 1.27 (1.21 to 1.33; I(2)=89%, n=11) among healthy never smokers with exclusion of early follow-up, and 1.05 (1.04 to 1.07; I(2)=97%, n=198) among all participants. There was a J shaped dose-response relation in never smokers (Pnon-linearity <0.001), and the lowest risk was observed at BMI 23-24 in never smokers, 22-23 in healthy never smokers, and 20-22 in studies of never smokers with ≥20 years' follow-up. In contrast there was a U shaped association between BMI and mortality in analyses with a greater potential for bias including all participants, current, former, or ever smokers, and in studies with a short duration of follow-up (<5 years or <10 years), or with moderate study quality scores. Overweight and obesity is associated with increased risk of all cause mortality and the nadir of the curve was observed at BMI 23-24 among never smokers, 22-23 among healthy never smokers, and 20-22 with longer durations of follow-up. The increased risk of mortality observed in underweight people could at least partly be caused by residual confounding from prediagnostic disease. Lack of exclusion of ever smokers, people with prevalent and preclinical disease, and early follow-up could bias the results towards a more U shaped association.


Loss of connexin43-mediated gap junctional coupling in the mesenchyme of limb buds leads to altered expression of morphogens in mice.
Mutations in the GJA1 gene coding for connexin43 (Cx43) cause oculodentodigital dysplasia (ODDD), a pleiotropic human disorder with characteristic morphologic anomalies of face, teeth, bones and digits. Interdigital webbings, also called syndactylies, are a characteristic phenotype of this disease showing high intra- and interfamilial penetrance. Therefore, we decided to study the molecular basis of syndactylies caused by Cx43 mutations. In order to reveal the impact of Cx43-mediated gap junctional coupling, we used mice expressing the human point mutation Cx43G138R and, in addition, 'knock-out' mice lacking Cx43. Both conditional mouse models developed syndactylies as a consequence of disturbed interdigital apoptosis, which we show to be due to reduced expression of two key morphogens: sonic hedgehog (Shh) and bone morphogenic protein 2 (Bmp2). Diminished levels of Bmp2 and subsequent up-regulation of fibroblast growth factors (Fgfs) lead to an insufficient induction of interdigital apoptosis. Interestingly, the reduction of Shh expression in Cx43 mutants begins on embryonic day 10.5 indicating a disturbance of the Fgf/Shh regulatory feedback loop, and confirming the recently published observation that gap junctions can relay Fgf signals to neighboring cells. Thus, Cx43-mediated gap junctional coupling in the mesenchyme of limb buds after ED11 is essential to maintain Shh expression, which regulates the downstream signaling of Bmp2. Besides diminished interdigital apoptosis, the decreased expression of Bmp2 in Cx43 mutants may also be involved in other morphological alterations in patients suffering from ODDD.


Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells.
The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (delta F508), corrected the Cl- channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease.


Evolution of the first metabolic cycles.
There are two alternatives concerning the origin of life: the origin may be heterotrophic or autotrophic. The central problem within the theory of an autotrophic origin is the first process of carbon fixation. I here propose the hypothesis that this process is an autocatalytic cycle that can be retrodictively constructed from the extant reductive citric acid cycle by replacing thioesters by thioacids and by assuming that the required reducing power is obtained from the oxidative formation of pyrite (FeS2). This archaic cycle is strictly chemoautotrophic: photoautotrophy is not required. The cycle is catalytic for pyrite formation and autocatalytic for its own multiplication. It is a consequence of this hypothesis that the postulated cycle cannot exist as a single isolated cycle but must be a member of a network of concatenated homologous cycles, from which all anabolic pathways appear to have sprung.


Tau isoform expression and phosphorylation in marmoset brains.
Tau is a microtubule-associated protein expressed in neuronal axons. Hyperphosphorylated tau is a major component of neurofibrillary tangles, a pathological hallmark of Alzheimer's disease (AD). Hyperphosphorylated tau aggregates are also found in many neurodegenerative diseases, collectively referred to as "tauopathies," and tau mutations are associated with familial frontotemporal lobar degeneration (FTLD). Previous studies have generated transgenic mice with mutant tau as tauopathy models, but nonhuman primates, which are more similar to humans, may be a better model to study tauopathies. For example, the common marmoset is poised as a nonhuman primate model for investigating the etiology of age-related neurodegenerative diseases. However, no biochemical studies of tau have been conducted in marmoset brains. Here, we investigated several important aspects of tau, including expression of different tau isoforms and its phosphorylation status, in the marmoset brain. We found that marmoset tau does not possess the "primate-unique motif" in its N-terminal domain. We also discovered that the tau isoform expression pattern in marmosets is more similar to that of mice than that of humans, with adult marmoset brains expressing only four-repeat tau isoforms as in adult mice but unlike in adult human brains. Of note, tau in brains of marmoset newborns was phosphorylated at several sites associated with AD pathology. However, in adult marmoset brains, much of this phosphorylation was lost, except for Ser-202 and Ser-404 phosphorylation. These results reveal key features of tau expression and phosphorylation in the marmoset brain, a potentially useful nonhuman primate model of neurodegenerative diseases.


Neurosarcoidosis with necrotising sarcoid granulomatosis mimicking meningiomatosis cerebri: case report and literature search.
A 52-year-old woman presented with headaches, difficulty with word finding and left eye blindness. MRI showed enhancing frontal dural-based masses suggestive of meningiomatosis. Biopsy and debulking revealed necrotising granulomas, without discernible micro-organisms or neoplasia; a thorough clinical work-up was negative for infection and vasculitis. A CT scan showed mild bilateral hilar lymphadenopathy, a tiny pulmonary nodule and cirrhotic liver. Her subsequent alteration of mental status was attributed to hepatic encephalopathy based upon elevated aminotransferase and ammonia levels, biopsy evidence of hepatoportal sclerosis with rare granulomas and response to lactulose. A diagnosis of neurosarcoidosis of the necrotising sarcoid granulomatosis variant (NS-NSG) with atypical systemic involvement was made. This is the fifth case report of NS-NSG clinically mimicking a neoplasm and histologically mimicking a mycobacterial infection. NS-NSG can have an atypical clinical picture including intracranial masses; a thorough work-up to exclude infectious and other non-infectious aetiologies is a prerequisite to its diagnosis.


Measurements of the modal properties of a diffractive-optic graded-phase resonator.
We measured the higher-order modes of a diffractive-optic graded-phase resonator by suppressing the lower-order modes of a flash-lamp-pumped Nd:YAG laser with spatial filters. A diffractive-optic end mirror was used to establish a flattop fundamental mode. Measurements of the fundamental and higher-order mode shapes agreed with theoretical models. Quantitative measurements of modal discrimination substantiate the predictions of large discrimination between the fundamental and second-order modes.


4-hydroxyequilenin-adenine lesions in DNA duplexes: stereochemistry, damage site, and structure.
The equine estrogens, equilin and equilenin, are major components of the drug Premarin, the most widely used formula for hormone replacement therapy. The derivative 4-hydroxyequilenin (4-OHEN), a major phase I metabolite of equilin and equilenin, autoxidizes to potent cytotoxic quinoids that can react in vitro and in vivo with cytosine and adenine in DNA. Unique cyclic adducts containing the same bicyclo[3.3.1]nonane-type connection ring are produced. Each base adduct has four stereoisomers. In order to elucidate the structural effects of A versus C modification, we have carried out molecular dynamics simulations of the stereoisomeric 4-OHEN-A adducts in DNA 11-mer duplexes and compared results with an earlier study of the C adducts (Ding, S., Shapiro, R., Geacintov, N.E., and Broyde, S. (2005) Equilenin-Derived DNA Adducts to Cytosine in DNA Duplexes: Structures and Thermodynamics, Biochemistry 44, 14565-14576). Similar stereochemical principles govern the orientations in DNA duplexes of the 4-OHEN-A adducts as for the analogous C adducts, with opposite orientations of the equilenin rings in stereoisomeric pairs of adducts characterized by near-mirror image circular dichroism (CD) spectra. However, the larger purine adducts have unique structural properties in the duplexes that distinguish their characteristics from those of the pyrimidine adducts. Significant differences are observed in terms of hydrogen bonding, stacking, bending, groove dimensions, solvent exposure, and hydrophobic interactions; also, each of the four stereoisomeric 4-OHEN-A adducts exhibit distinct structural features. Each base adduct and stereoisomer distorts the structure of the DNA duplex differently. These characteristics may manifest themselves in terms of differential nucleotide excision repair susceptibilities and mutagenic activities of the 4-OHEN-A and C adducts.


3D Standard Brain of the Red Flour Beetle Tribolium Castaneum: A Tool to Study Metamorphic Development and Adult Plasticity.
The red flour beetle Tribolium castaneum is emerging as a further standard insect model beside Drosophila. Its genome is fully sequenced and it is susceptible for genetic manipulations including RNA-interference. We use this beetle to study adult brain development and plasticity primarily with respect to the olfactory system. In the current study, we provide 3D standard brain atlases of freshly eclosed adult female and male beetles (A0). The atlases include eight paired and three unpaired neuropils including antennal lobes (ALs), optic lobe neuropils, mushroom body calyces and pedunculi, and central complex. For each of the two standard brains, we averaged brain areas of 20 individual brains. Additionally, we characterized eight selected olfactory glomeruli from 10 A0 female and male beetles respectively, which we could unequivocally recognize from individual to individual owing to their size and typical position in the ALs. In summary, comparison of the averaged neuropil volumes revealed no sexual dimorphism in any of the reconstructed neuropils in A0 Tribolium brains. Both, the female and male 3D standard brain are also used for interspecies comparisons, and, importantly, will serve as future volumetric references after genetical manipulation especially regarding metamorphic development and adult plasticity.


Clinical Trial Registry Use in Orthopaedic Surgery Systematic Reviews.
Results from systematic reviews and meta-analyses, which have the highest level of evidence (Level I), often drive clinical decision-making and health policy. Often, unpublished trial data are omitted from systematic reviews, raising concerns about the extent of the reliability and validity of results that have been drawn from systematic reviews. We aimed to determine the extent to which systematic review authors include searches of clinical trial registries for unpublished data when conducting systematic reviews in orthopaedic surgery. Systematic reviews and/or meta-analyses were gathered from the top 5 orthopaedic surgery journals based on the h5-index from Google Scholar Metrics. Systematic reviews that had been published in the Cochrane Database of Systematic Reviews, which requires the inclusion of a clinical trial registry search, served as controls. For the primary outcome, each systematic review from the top 5 orthopaedic journals was screened to determine whether the authors of each study searched for unpublished data in clinical trial registries. We then compared the rate of registry searches with those in the control group. For the secondary analysis, a search of ClinicalTrials.gov was performed for unpublished trial data for 100 randomized systematic reviews. All 38 of the Cochrane systematic reviews (100%) included clinical trial registry searches, while the top 5 orthopaedic journals had only 31 of 480 studies (6.5%) that looked at clinical trial registries. The secondary analysis yielded 59 of 100 systematic review articles (59.0%) that could have included unpublished clinical trial data from ≥1 studies to their sample. Systematic reviews that have been published in the top orthopaedic surgery journals seldom included a search for unpublished clinical trial data. The exclusion of clinical trial registry searches potentially contributes to publication bias within the orthopaedic literature. Moving forward, systematic review authors should include clinical trial registry searches for unpublished clinical trial data to provide the most accurate representation of the available evidence for systematic reviews and meta-analyses.


Is Hybridization a Source of Adaptive Venom Variation in Rattlesnakes? A Test, Using a Crotalus scutulatus × viridis Hybrid Zone in Southwestern New Mexico.
Venomous snakes often display extensive variation in venom composition both between and within species. However, the mechanisms underlying the distribution of different toxins and venom types among populations and taxa remain insufficiently known. Rattlesnakes (Crotalus, Sistrurus) display extreme inter- and intraspecific variation in venom composition, centered particularly on the presence or absence of presynaptically neurotoxic phospholipases A₂ such as Mojave toxin (MTX). Interspecific hybridization has been invoked as a mechanism to explain the distribution of these toxins across rattlesnakes, with the implicit assumption that they are adaptively advantageous. Here, we test the potential of adaptive hybridization as a mechanism for venom evolution by assessing the distribution of genes encoding the acidic and basic subunits of Mojave toxin across a hybrid zone between MTX-positive Crotalus scutulatus and MTX-negative C. viridis in southwestern New Mexico, USA. Analyses of morphology, mitochondrial and single copy-nuclear genes document extensive admixture within a narrow hybrid zone. The genes encoding the two MTX subunits are strictly linked, and found in most hybrids and backcrossed individuals, but not in C. viridis away from the hybrid zone. Presence of the genes is invariably associated with presence of the corresponding toxin in the venom. We conclude that introgression of highly lethal neurotoxins through hybridization is not necessarily favored by natural selection in rattlesnakes, and that even extensive hybridization may not lead to introgression of these genes into another species.


Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation.
Prostaglandin E(2) (PGE(2)) inhibits lymphocyte proliferation and the production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells, but the effect of PGE(2) on interleukin 4 (IL-4) production is unclear. Fish oil, which contains eicosapentaenoic and docosahexaenoic acids, inhibits production of PGE(2). The effects of fish oil on lymphocyte proliferation and production of IFN-gamma and IL-4 are unclear and may be influenced by the availability of antioxidants. We investigated the effect of dietary fish oil with and without antioxidant cosupplementation on lymphocyte proliferation and the production of PGE(2), IFN-gamma, and IL-4 by peripheral blood mononuclear cells. Sixteen healthy men received dietary fish-oil supplements providing 0.3, 1, and 2 g eicosapentaenoic acid plus docosahexaenoic acid/d for 4 consecutive weeks each (total of 12 wk). All subjects were randomly assigned to daily cosupplementation with either antioxidants (200 microg Se, 3 mg Mn, 30 mg RRR-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 micro g vitamin A) or placebo. Fish-oil supplementation decreased PGE(2) production and increased IFN-gamma production and lymphocyte proliferation from baseline values. Cosupplementation with antioxidants did not affect cytokine production or lymphocyte proliferation. Dietary fish oil modulates production of IFN-gamma and lymphocyte proliferation in a manner consistent with decreased production of PGE(2), but this effect is not modified by antioxidant cosupplementation.


A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain.
To evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain. Prospective, randomized, double-blind, placebo-controlled trial. Seventy-nine US and Canadian centers. Patients aged ≥ 18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week. Patients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8. Among randomized patients (N=418; lubiprostone, N=210; placebo, N=208), most completed the study (lubiprostone, 67.1%; placebo, 69.7%). The safety and efficacy (intent-to-treat) populations included 414 (lubiprostone, N=208; placebo, N=206) and 413 (lubiprostone, N=209; placebo, N=204) patients, respectively. The mean (standard deviation) age was 50.4 (10.9) years; most patients were female (64.4%) and white (77.7%). Changes from baseline in SBM frequency rates were significantly higher at week 8 (P=0.005) and overall (P=0.004) in patients treated with lubiprostone compared with placebo. Pairwise comparisons showed significantly greater overall improvement for abdominal discomfort (P=0.047), straining (P<0.001), constipation severity (P=0.007), and stool consistency (P<0.001) with lubiprostone compared with placebo. Moreover, patients rated the effectiveness of lubiprostone as significantly (P<0.05) better than placebo for 11 of 12 weeks. The most common treatment-related adverse events (AEs) with lubiprostone and placebo were nausea (16.8% vs 5.8%, respectively), diarrhea (9.6% vs 2.9%), and abdominal distention (8.2% vs 2.4%). No lubiprostone-related serious AEs occurred. Lubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946).


Risk factors for different histological types of ovarian cancer.
Various histological types of ovarian cancer may develop from different etiological aspects. Data separated by histological subtypes collected in the framework of a large case-control study on ovarian cancer conducted in Italy were analyzed. The cases were women below the age of 75 years, admitted to a network of hospitals in Milan. Cases were grouped into four categories by histological type: mucinous tumor (n = 52), serous tumor (n = 680), endometrioid tumor (n = 41), and other histologies including clear-cell and undifferentiated epithelial tumors (n = 50). Controls were 2758 patients admitted to the same network of hospitals for a wide spectrum of acute, nongynecological, non-hormone-related, non-neoplastic conditions. In comparison with nulliparae, the risk of serous, endometrioid, and other histologies of ovarian cancer tended to be lower in parous women, but the odds ratios (OR) were above unity for mucinous ovarian cancer. Oral contraceptive use was associated with OR lower than unity for serous (OR = 0.7) and endometrioid (OR = 0.8) ovarian cancers but not for mucinous (OR = 1.4) and other histologies (OR = 1.6). Finally, our results on dietary fat intake did not show substantial differences in all histological types of ovarian cancer.


Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage.
Pore forming proteins such as those belonging to the membrane attack/perforin (MACPF) family have important functions in many organisms. Of the five MACPF proteins found in Plasmodium parasites, three have functions in cell passage and one in host cell egress. Here we report an analysis of the perforin-like protein 4, PPLP4, in the rodent parasite Plasmodium berghei. We found that the protein is expressed only in the ookinete, the invasive stage of the parasite formed in the mosquito midgut. Transcriptional analysis revealed that expression of the pplp4 gene commences during ookinete development. The protein was detected in retorts and mature ookinetes. Using two antibodies, the protein was found localized in a dotted pattern, and 3-D SIM super-resolution microcopy revealed the protein in the periphery of the cell. Analysis of a C-terminal mCherry fusion of the protein however showed mainly cytoplasmic label. A pplp4 null mutant formed motile ookinetes, but these were unable to invade and traverse the midgut epithelium resulting in severely impaired oocyst formation and no transmission to naïve mice. However, when in vitro cultured ookinetes were injected into the thorax of the mosquito, thus by-passing midgut passage, sporozoites were formed and the mutant parasites were able to infect naïve mice. Taken together, our data show that PPLP4 is required only for ookinete invasion of the mosquito midgut. Thus PPLP4 has a similar role to the previously studied PPLP3 and PPLP5, raising the question why three proteins with MACPF domains are needed for invasion by the ookinete of the mosquito midgut epithelium.


The Copenhagen Psychosocial Questionnaire--a tool for the assessment and improvement of the psychosocial work environment.
The aim of this article is to present the Copenhagen Psychosocial Questionnaire (COPSOQ), a questionnaire developed in three different lengths for assessing psychosocial factors at work, stress, and the well-being of employees and some personality factors. The purpose of the COPSOQ concept is to improve and facilitate research, as well as practical interventions at workplaces. The development of the questionnaire was based on a survey of a representative sample of 1858 Danish employees aged 20-59 years. The response rate was 62%; 49% were women. Altogether 145 questions from some international and Danish questionnaires and 20 self-developed questions were tested with factor analyses, analyses of internal reliability, and analyses of response patterns. The analyses resulted in a long research version of the questionnaire with 141 questions and 30 dimensions, a medium-length version for work environment professionals with 95 questions and 26 dimensions, and a short version for workplaces with 44 questions and 8 dimensions. Most of the scales have good reliability, and there seems to be very little overlap between the scales. A novel feature of the COPSOQ is the development of five different scales on demands at work. The COPSOQ concept is a valid and reliable tool for workplace surveys, analytic research, interventions, and international comparisons. The questionnaire seems to be comprehensive and to include most of the relevant dimensions according to several important theories on psychosocial factors at work. The three versions facilitate communication between researchers, work environment professionals, and workplaces.


Food Grade Pimenta Leaf Essential Oil Reduces the Attachment of Salmonella enterica Heidelberg (2011 Ground Turkey Outbreak Isolate) on to Turkey Skin.
Salmonella attached to the poultry skin is a major source of carcass contamination during processing. Once attached to the poultry skin, it is difficult to detach and inactivate Salmonella by commonly used antimicrobial agents since the pathogen is entrapped deeply in the feather follicles and the crevices on the skin. Essential oils could be natural, safe, and effective alternatives to synthetic antimicrobial agents during commercial and organic processing setup. The present study evaluated the efficacy of pimenta (Pimenta officinalis Lindl.) leaf essential oil (PEO), and its nanoemulsion in reducing Salmonella Heidelberg attachment on to turkey (Meleagris gallopavo) skin during simulated scalding (65°C) and chilling (4°C) steps in poultry processing. A multidrug resistant S. Heidelberg isolate from the 2011 ground turkey outbreak in the United States was used in the study. Results showed that PEO and the nanoemulsion resulted in significant reduction of S. Heidelberg attachment on turkey skin. Turkey skin samples treated with 1.0% PEO for 5 min resulted in >2 log10 CFU/sq. inch reduction of S. Heidelberg at 65 and 4°C, respectively (n = 6; P < 0.05). Similarly, skin samples treated with 1.0% pimenta nanoemulsion (PNE) for 5 min resulted in 1.5- and 1.8- log10 CFU/sq. inch reduction of S. Heidelberg at 65 and 4°C, respectively (n = 6; P < 0.05). In addition, PEO and PNE were effective in reducing S. Heidelberg on skin during short-term storage at 4 and 10°C (temperature abuse) (n = 6; P < 0.05). No Salmonella was detected in the dipping solution containing 0.5 or 1.0% PEO or PNE, whereas a substantial population of the pathogen survived in the control dipping solution. The results were validated using scanning electron -, and confocal - microscopy techniques. PEO or PNE could be utilized as an effective antimicrobial agent to reduce S. Heidelberg attachment to turkey skin during poultry processing.


Cancer mortality among shoe manufacturing workers: an analysis of two cohorts.
To examine the cancer risk of shoe manufacturing workers and evaluate whether the risk was associated with exposure to leather dust and solvents. Data from two historical cohort studies of shoe workers were expanded and analysed in parallel. A total of 4215 shoemakers from England contributing 103 726 person-years at risk and 2008 shoemakers from Florence, Italy, contributing 54,395 person-years at risk were included in the analysis. Exposure to leather dusts and solvents from glues was evaluated on the basis of job title information. Standardised mortality ratios (SMR) were calculated as ratios of observed deaths (Obs) over expected derived from national mortalities. Overall mortality was lower than expected in both cohorts (English cohort: Obs 3314, SMR 81, 95% confidence interval (95% CI) 78-84; Florence cohort: Obs 333, SMR 87, 95% CI 78-97). An increased risk of nasal cancer was found (English cohort: Obs 12, SMR 741; Florence cohort: Obs 1, SMR 909). 10 of the 13 cases occurred among English workers employed in the manufacture of welted boots (SMR 926, 95% CI 444-1703), a sector of the industry thought to have had the highest exposure to leather dust. Mortality from leukaemia was not increased in the English cohort (Obs 16, SMR 89), but was increased in the Florence cohort (Obs 8, SMR 214, 95% CI 92-421); and the highest risk was found among shoe workers in Florence who were first exposed between 1950 and 1959 when exposure to benzene was substantial (Obs 3, SMR 536, 95% CI 111-1566). Some evidence for an excess risk of stomach, bladder, and kidney cancer, as well as multiple myeloma and non-Hodgkin's lymphoma was also found in the Florence cohort only among workers employed in jobs with the highest exposure to solvents. These findings confirm the associations between exposure to leather dust and nasal cancer and between exposure to benzene and leukaemia in the shoe manufacturing industry and suggest that the risk of other cancers may be increased among workers exposed to solvents or glues.


Economic savings and costs of periodic mammographic screening in the workplace.
This article discusses the costs and benefits of mammographic screening in the workplace. The cost of mammography itself and of diagnostic work-up are two of the largest costs involved. Therefore, the most efficient approach to providing mammography depends on the number of employees receiving mammography; and the diagnostic accuracy of mammography and underlying incidence of breast cancer in the screened population strongly influence the number of suspicious mammograms that are not associated with breast cancer. The health benefit of mammographic screening is due to reduced mortality and morbidity through early detection and more effective treatment, which may also result in economic savings if early-stage cancer is less expensive to treat. However, the total lifetime cost of treating early-stage cancer may be greater than treating late-stage cancer because of improved survival of early-stage patients. Thus, although periodic mammographic screening is not likely to result in overall economic savings, in many populations of working-age women, especially those with identifiable risk factors, screening is cost-effective because the expenditure required to save a year of life through early detection of breast cancer is low compared to other types of health services for which employers commonly pay.


Decoding the ocean's microbiological secrets for marine enzyme biodiscovery.
A global census of marine microbial life has been underway over the past several decades. During this period, there have been scientific breakthroughs in estimating microbial diversity and understanding microbial functioning and ecology. It is estimated that the ocean, covering 71% of the earth's surface with its estimated volume of about 2 × 1018 m3 and an average depth of 3800 m, hosts the largest population of microbes on Earth. More than 2 million eukaryotic and prokaryotic species are thought to thrive both in the ocean and on its surface. Prokaryotic cell abundances can reach densities of up to 1012 cells per millilitre, exceeding eukaryotic densities of around 106 cells per millilitre of seawater. Besides their large numbers and abundance, marine microbial assemblages and their organic catalysts (enzymes) have a largely underestimated value for their use in the development of industrial products and processes. In this perspective article, we identified critical gaps in knowledge and technology to fast-track this development. We provided a general overview of the presumptive microbial assemblages in oceans, and an estimation of what is known and the enzymes that have been currently retrieved. We also discussed recent advances made in this area by the collaborative European Horizon 2020 project 'INMARE'.


Etiology, Risk Factors and Outcome of 1003 Cases of Infective Endocarditis from a 33-year National Survey in the Slovak Republic: An increasing proportion of elderly patients.
Infective endocarditis (IE) is still a significant cause of mortality in European hospitals, despite of the fact, that large nationwide studies were performed in last twenty years and pathogens are well known. The aim of the study was to assess risk factors, mortality, etiology and proportion of elderly patients within a longitudinal nation wide survey of infectious endocarditis in Slovakia. Etiology, risk factors and outcome of 1003 cases of infective endocarditis (IE) in Slovakia over the last 33 years have been assessed. The majority of IE were caused by Staphylococci (28.3%), 15.6% were due to Viridans streptococci, 10% due to Enterococci, 8.2% by gram-negative bacteria, Acinetobacter baumannii and Pseudomonas aeruginosa, 3.7% by other organisms and 31.0% of all cases were culture negative. The following risk factors were recorded: age > 65 (36.8%), rheumatic fever (15.3%), dental surgery (8.7%), previous non-cardiological surgery (8.2 %), neoplasia (8.1%), diabetes (7.8%), any endoscopy (8.5%) and dialysis (4.6%). All patients were treated with antimicrobials, 507 (51%) also with surgery. Survival rate at day 60 after diagnosis was 88.1% (n=883). Only age >65 (34.3% vs. 49.5%, p=0.045) and persistent bacteremia (with three or more positive blood cultures 15.7% vs. 34.5%, p=0,001) were significantly associated with higher attributable mortality. Concerning risk factors, etiology and therapeutic strategies, rheumatic fever and neoplasia showed decrease in tendency. Dental surgery and tonsillitis were less frequent as well (26.7% vs. 2%, p<0,001 and 16% vs. 1%, p<0.001). There was a significant shift in etiology after 1997: culture-negative endocarditis was surprisingly more frequently observed in the 2007-2017 period than before and represented 10.7% of all cases in 1984-1990 in comparison to 25.1-25.6% in 2007-2010 and 2011-2017. Staphylococci decreased from 48% to 29.6% (2007-2017), but are still major pathogens. Persistent bacteremia (3 or more positive blood cultures 5.3% vs. 24.7%, p<0,001) was less commonly observed within the 1st period (1984-1990) in comparison to 2007-2010. More patients in the 1st period (1984-1990) had embolization complications of IE than in the fifth and sixth period (2007-2017) (76 vs. 16.3% p<0.001). CNS embolization decreased from 14% to less than 5% (p<0.003). Attributable mortality was lower too (26.7% vs. 9.5%, p<0.001) because of increased proportion of cardiac surgery in the treatment of IE in 2007-2017 in comparison to 1984-1990. Study has showed significant shifts in etiology, risk factors and complications over the observed time periods in Slovakia.


Subsequent Injury Risk Is Elevated Above Baseline After Return to Play: A 5-Year Prospective Study in Elite Australian Football.
The risk of sustaining a subsequent injury is elevated in the weeks after return to play (RTP) from an index injury. However, little is known about the magnitude, duration, and nature by which subsequent injury risk is increased. To quantify and describe the risk of injury in a 12-week period after RTP from an index injury in Australian football players. Cohort study; Level of evidence, 2. Injury data were collected from 79 players over 5 years at 1 Australian Football League club. Injuries were classified with the Orchard Sports Injury Classification System and by side of the body. Furthermore, injury severity was classified as time loss (resulting in ≥1 matches being missed) or non-time loss (no matches missed). Subsequent injury was categorized with the SIC-2.0 model and applied to the data set via an automated script. The probability of a time loss subsequent injury was calculated for in-season index injuries for each week of a 12-week period after RTP via a mixed effect logistic regression model. Subsequent injury risk was found to be highest in the week of RTP for both time loss injuries (9.4%) and non-time loss injuries (6.9%). Risk decreased with each week survived after RTP; however, it did not return to baseline risk of participation (3.6%). These findings demonstrate that athletes returning to play are at an increased risk of injury for a number of weeks, thus indicating the requirement for tertiary prevention strategies to ensure that they survive this period.


Successes and drawbacks in the caries-preventive use of fluorides--lessons to be learnt from history.
Water fluoridation was the first breakthrough in the practice of preventive cariology on a community level and has remained one of the cornerstones of prevention in dentistry. The concepts regarding the mechanisms of the caries-inhibitory effect, however, have changed in several respects. Today there is general agreement that topical effects on the erupted enamel are most important. The contention that there is no pre-eruptive effect whatsoever has created confusion; there is in fact evidence for a minor pre-eruptive protective effect. Around 1980 many experts believed that fluorides should not be used in high concentrations, for instance above those in dentifrices, because this could block remineralisation in the body of pre-cavity lesions. However, it is now known that such undesirable effects are negligible or non-existent. In the fifties and sixties, fluoride tablets were widely used in Europe and helped to make the concept of caries prevention popular. From 1980 onwards, fluoride dentifrices were found to have a much greater impact and were recognized as being able to lead to a decline of caries prevalence in entire countries, and fluoride tablets gradually lost their importance. Antifluoridationists were unable to delay or hinder the widespread use of fluoride toothpastes but in many cases have successfully opposed public health measures such as fluoridation of water or of salt. The spread of these methods, beneficial for all social strata, might have been more rapid if some of the experts had not propounded the erroneous supposition that fluoride dentifrice will be sufficient for caries prevention. Sale of fluoridated salt has been authorized in several countries on a nationwide scale. However, only Latin American countries have introduced salt fluoridation for entire populations. In Central and Eastern Europe where caries prevalence continues to be high and where the level of usage of topical fluorides including dentifrices will presumably remain at a low level for many years, salt fluoridation would be beneficial.


Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration.
Coordinated migration of newly born neurons to their prospective target laminae is a prerequisite for neural circuit assembly in the developing brain. The evolutionarily conserved LIS1/NDEL1 complex is essential for neuronal migration in the mammalian cerebral cortex. The cytoplasmic nature of LIS1 and NDEL1 proteins suggest that they regulate neuronal migration cell autonomously. Here, we extend mosaic analysis with double markers (MADM) to mouse chromosome 11 where Lis1, Ndel1, and 14-3-3ɛ (encoding a LIS1/NDEL1 signaling partner) are located. Analyses of sparse and uniquely labeled mutant cells in mosaic animals reveal distinct cell-autonomous functions for these three genes. Lis1 regulates neuronal migration efficiency in a dose-dependent manner, while Ndel1 is essential for a specific, previously uncharacterized, late step of neuronal migration: entry into the target lamina. Comparisons with previous genetic perturbations of Lis1 and Ndel1 also suggest a surprising degree of cell-nonautonomous function for these proteins in regulating neuronal migration.


Paroxysmal atrial fibrillation in young and middle-aged athletes (PAFIYAMA) syndrome in the real world: a paradigmatic case report.
An enhanced risk of atrial fibrillation (AF) has been clearly documented in endurance athletes over the past decades. In this regard, we have recently described the 'PAFIYAMA' ('paroxysmal AF in young and middle-aged athletes') syndrome, provided that other risk factors for AF and underlying conditions have been ruled out. We report here a paradigmatic case of PAFIYAMA syndrome. A 32 years old man was admitted to the Emergency Department (ED) complaining for palpitations, lasting for 3 hours. He had never smoked and other risk factors for AF could be ruled out. The electrocardiogram (ECG) was consistent with AF at high ventricular response (130-150 bpm). All laboratory parameters were within the respective reference ranges, and laboratory screening for cocaine, amphetamine, and MDMA was negative. After 12 hours of persistent AF, the patient underwent effective electrical cardioversion. The patient reported an episode of paroxysmal AF (PAF), occurred during practicing strenuously training for a martial arts competition 2 years before the current episode. In the last two weeks, in addition to usual training, the patient was engaged in carrying heavy furniture. He underwent echocardiography within a week from ED discharge, showing a physiologic athlete's left ventricle (LV) hypertrophy. The patient was discharged with suggestion to reduce his training regimen. A Holter-ECG performed one month after ED discharge showed no signs of arrhythmia, and the patient remained asymptomatic during the following six months of follow-up. Therefore, following the diagnostic algorithm of PAFIYAMA syndrome, this patient can be considered as a paradigmatic case of this recently described syndrome. The potential clinical implications and the impact on patients' lifestyle are meaningful. New-onset AF in young population is uncommon. For that reason, physicians should be aware about PAFIYAMA syndrome.


Patient data ownership: who owns your health?
This article answers two questions from the perspective of United Kingdom law and policy: (i) is health information property? and (ii) should it be? We argue that special features of health information make it unsuitable for conferral of property rights without an extensive system of data-specific rules, like those that govern intellectual property. Additionally, we argue that even if an extensive set of rules were developed, the advantages of a property framework to govern health information would be slight: propertization is unlikely to enhance patient self-determination, increase market efficiency, provide patients a foothold in the data economy, clarify legal uses of information, or encourage data-driven innovation. The better approach is to rely less, not more, on property. We recommend a regulatory model with four signature features: (i) substantial protection for personal health data similar to the GDPR with transparent limits on how, when, and by whom patient data can be accessed, used, and transmitted; (ii) input from relevant stakeholders; (iii) interoperability; and (iv) greater research into a health-data service, rather than goods, model.


Nutrient-regulated transcriptional responses in the brown tide-forming alga Aureococcus anophagefferens.
Long-SAGE (serial analysis of gene expression) was used to profile the transcriptome of the brown tide-forming alga, Aureococcus anophagefferens, under nutrient replete (control), and nitrogen (N) and phosphorus (P) deficiency to understand how this organism responds at the transcriptional level to varying nutrient conditions. This approach has aided A. anophagefferens genome annotation efforts and identified a suite of genes upregulated by N and P deficiency, some of which have known roles in nutrient metabolism. Genes upregulated under N deficiency include an ammonium transporter, an acetamidase/formamidase and two peptidases. This suggests an ability to utilize reduced N compounds and dissolved organic nitrogen, supporting the hypothesized importance of these N sources in A. anophagefferens bloom formation. There are also a broad suite of P-regulated genes, including an alkaline phosphatase, and two 5'-nucleotidases, suggesting A. anophagefferens may use dissolved organic phosphorus under low phosphate conditions. These N- and P-regulated genes may be important targets for exploring nutrient controls on bloom formation in field populations.


Intensive comprehensive aphasia programs: an international survey of practice.
In response to the need to simultaneously address multiple domains of the International Classification of Functioning, Disability and Health (ICF) in aphasia therapy and to incorporate intensive treatment doses consistent with principles of neuroplasticity, a potentially potent treatment option termed intensive comprehensive aphasia programs (ICAPs) has been developed. To conduct an international survey of ICAPs to determine the extent of their use and to explore current ICAP practices. A 32-item online survey was distributed internationally through Survey Monkey between May and August 2012. The survey addressed ICAP staffing, philosophy, values, funding, admission criteria, activities, family involvement, outcome measures, and factors considered important to success. Twelve ICAPs responded: 8 from the United States, 2 from Canada, and 1 each from Australia and the United Kingdom. The majority of ICAPs are affiliated with university programs and are funded through participant self-pay. ICAPs emphasize individualized treatment goals and evidence-based practices, with a focus on applying the principles of neuroplasticity related to repetition and intensity of treatment. On average, 6 people with aphasia attend each ICAP, for 4 days per week for 4 weeks, receiving about 100 hours of individual, group, and computer-based treatment. Speech-language pathologists, students, and volunteers staff the majority of ICAPs. ICAPs are increasing in number but remain a rare service delivery option. They address the needs of individuals who want access to intensive treatment and are interested in making significant changes to their communication skills and psychosocial well-being in a short period of time. Their efficacy and cost-effectiveness require future investigation.


Modelling inhalation exposure to combustion-related air pollutants in residential buildings: Application to health impact assessment.
Buildings in developed countries are becoming increasingly airtight as a response to stricter energy efficiency requirements. At the same time, changes are occurring to the ways in which household energy is supplied, distributed and used. These changes are having important impacts on exposure to indoor air pollutants in residential buildings and present new challenges for professionals interested in assessing the effects of housing on public health. In many circumstances, models are the most appropriate way with which to examine the potential outcomes of future environmental and/or building interventions and policies. As such, there is a need to consider the current state of indoor air pollution exposure modelling. Various indoor exposure modelling techniques are available, ranging from simple statistical regression and mass-balance approaches, to more complex multizone and computational fluid dynamics tools that have correspondingly large input data requirements. This review demonstrates that there remain challenges which limit the applicability of current models to health impact assessment. However, these issues also present opportunities for better integration of indoor exposure modelling and epidemiology in the future. The final part of the review describes the application of indoor exposure models to health impact assessments, given current knowledge and data, and makes recommendations aimed at improving model predictions in the future.


Ultrasensitive Detection of Volatile Organic Compounds by a Pore Tuning Approach Using Anisotropically Shaped SnO2 Nanocrystals.
Gas sensing with oxide nanostructures is increasingly important to detect gaseous compounds for safety monitoring, process controls, and medical diagnostics. For such applications, sensor sensitivity is one major criterion. In this study, to sensitively detect volatile organic compounds (VOCs) at very low concentrations, we fabricated porous films using SnO2 nanocubes (13 nm) and nanorods with different rod lengths (50-500 nm) that were synthesized by a hydrothermal method. The sensor response to H2 increased with decreasing crystal size; the film made of the smallest nanocubes showed the best sensitivity, which suggested that the H2 sensing is controlled by crystal size. In contrast, the responses to ethanol and acetone increased with increasing crystal size and resultant pore size; the highest sensitivity was observed for a porous film using the longest nanorods. Using the Knudsen diffusion-surface reaction equation, the gas sensor responses to ethanol and acetone were simulated and compared with experimental data. The simulation results proved that the detection of ethanol and acetone was controlled by pore size. Finally, we achieved ultrahigh sensitivity to ethanol; the sensor response (S) exceeded S = 100 000, which corresponds to an electrical resistance change of 5 orders of magnitude in response to 100 ppm of ethanol at 250 °C. The present approach based on pore size control provides a basis for designing highly sensitive films to meet the criterion for practical sensors that can detect a wide variety of VOCs at ppb concentrations.


Shallow slip amplification and enhanced tsunami hazard unravelled by dynamic simulations of mega-thrust earthquakes.
The 2011 Tohoku earthquake produced an unexpected large amount of shallow slip greatly contributing to the ensuing tsunami. How frequent are such events? How can they be efficiently modelled for tsunami hazard? Stochastic slip models, which can be computed rapidly, are used to explore the natural slip variability; however, they generally do not deal specifically with shallow slip features. We study the systematic depth-dependence of slip along a thrust fault with a number of 2D dynamic simulations using stochastic shear stress distributions and a geometry based on the cross section of the Tohoku fault. We obtain a probability density for the slip distribution, which varies both with depth, earthquake size and whether the rupture breaks the surface. We propose a method to modify stochastic slip distributions according to this dynamically-derived probability distribution. This method may be efficiently applied to produce large numbers of heterogeneous slip distributions for probabilistic tsunami hazard analysis. Using numerous M9 earthquake scenarios, we demonstrate that incorporating the dynamically-derived probability distribution does enhance the conditional probability of exceedance of maximum estimated tsunami wave heights along the Japanese coast. This technique for integrating dynamic features in stochastic models can be extended to any subduction zone and faulting style.


Arteriovenous fistula of the wrist after transradial coronary intervention.
The transradial approach for percutaneous coronary intervention (PCI) is a common route, but is associated with a few local complications. Access site complications, such as hematoma, radial artery spasm, and a reduced radial pulse, are reported frequently. However, an arteriovenous fistula (AVF) in the wrist related to the procedure is extremely rare. We encountered an AVF of the wrist after a transradial coronary intervention (TRI). The patient complained of a thrill detected in his right wrist, 2 months after TRI. Color Doppler ultrasonography demonstrated an AVF with a high turbulent velocity at the site of communication that required surgical revision. This appears to be a very unusual complication related to the transradial approach for PCI.


Allometry and Ecology of the Bilaterian Gut Microbiome.
Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (Bilateria) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction.IMPORTANCE The intestinal microbiome of animals is essential for health, contributing to digestion of foods, proper immune development, inhibition of pathogen colonization, and catabolism of xenobiotic compounds. How these communities assemble and persist is just beginning to be investigated. Here we interrogated a set of gut samples from a wide range of animals to investigate the roles of selection and random processes in microbial community construction. We show that the numbers of bacterial species increased with the weight of host organisms, paralleling findings from studies of island biogeography. Communities in larger organisms tended to be more anaerobic, suggesting one mechanism for niche diversification. Nonselective processes enable specific predictions for community structure, but our samples did not match the predictions of the neutral model. Thus, these findings highlight the importance of niche selection in community construction and suggest mechanisms of niche diversification.


Genetic developments in autoimmune thyroid disease: an evolutionary process.
The identification of genes placing individuals at an increased risk for the development of autoimmune thyroid disease (AITD) has been a slow process. However, over the last 20 years or so real progress has been made with the mapping of novel loci, via a number of different approaches. First, through the use of traditional immunological methods, Human Leucocyte Antigen (HLA)/Major Histocompatibility Complex (MHC) was the first gene region to be associated with AITD and consistent replications have been reported. Second, the CTLA-4 gene region on 2q33 was the first non-MHC replicated locus to be primarily identified using the candidate gene method. Third, family-based linkage studies led to the mapping of a new type 1 diabetes locus, the PTPN22 gene, which has subsequently been independently replicated as a susceptibility gene for Graves' disease (GD). Fourth, despite many unsuccessful attempts at implicating the TSHR gene as a susceptibility locus for GD, a recent approach of 'tagging' all the common variation within the gene has led to its identification as the first GD specific locus. Moreover, the use of tag single nucleotide polymorphisms (SNPs) has also been used to implicate the recently identified type 1 diabetes locus, CD25 as a susceptibility gene for GD. Finally, large scale, ongoing genome-wide association studies in multiple autoimmune diseases (AID) states, including AITD seem likely to lead to the identification of additional MHC and non-MHC susceptibility loci.


Suicide justice: Adopting Indigenous feminist methods in settler suicidology.
White settler colonies around the world have long reported disproportionately high rates of Indigenous suicides, a consequence of the continuing violence of imperialism. This article posits a need for interdisciplinary approaches to address this crisis and therefore turns to humanist methods developed in Indigenous and feminist scholarship. I analyze texts from U.S. psychologist Edwin Shneidman to rearticulate their relationship to what I call settler suicidology. I then evoke literary critic Eve K. Sedgwick's reparative reading method to reimagine suicide prevention as suicide justice, reading the novel There There by Tommy Orange (Cheyenne and Arapaho) to advocate for distributive justice as a new approach to Indigenous suicide crises. My term suicide justice names increasing accountability between settler suicide workers and the communities they seek to serve.


GWAS to Identify Genetic Loci for Resistance to Yellow Rust in Wheat Pre-Breeding Lines Derived From Diverse Exotic Crosses.
Yellow rust (YR) or stripe rust, caused by Puccinia striformis f. sp tritici Eriks (Pst), is a major challenge to resistance breeding in wheat. A genome wide association study (GWAS) was performed using 22,415 single nucleotide polymorphism (SNP) markers and 591 haplotypes to identify genomic regions associated with resistance to YR in a subset panel of 419 pre-breeding lines (PBLs) developed at International Center for Maize and Wheat Improvement (CIMMYT). The 419 PBLs were derived from an initial set of 984 PBLs generated by a three-way crossing scheme (exotic/elite1//elite2) among 25 best elites and 244 exotics (synthetics, landraces) from CIMMYT's germplasm bank. For the study, 419 PBLs were characterized with 22,415 high-quality DArTseq-SNPs and phenotyped for severity of YR disease at five locations in Mexico. A population structure was evident in the panel with three distinct subpopulations, and a genome-wide linkage disequilibrium (LD) decay of 2.5 cM was obtained. Across all five locations, 14 SNPs and 7 haplotype blocks were significantly (P < 0.001) associated with the disease severity explaining 6.0 to 14.1% and 7.9 to 19.9% of variation, respectively. Based on average LD decay of 2.5 cM, identified 14 SNP-trait associations were delimited to seven quantitative trait loci in total. Seven SNPs were part of the two haplotype blocks on chromosome 2A identified in haplotypes-based GWAS. In silico analysis of the identified SNPs showed hits with interesting candidate genes, which are related to pathogenic process or known to regulate induction of genes related to pathogenesis such as those coding for glunolactone oxidase, quinate O-hydroxycinnamoyl transferase, or two-component histidine kinase. The two-component histidine kinase, for example, acts as a sensor in the perception of phytohormones ethylene and cytokinin. Ethylene plays a very important role in regulation of multiple metabolic processes of plants, including induction of defense mechanisms mediated by jasmonate. The SNPs linked to the promising genes identified in the study can be used for marker-assisted selection.


Identification of a novel iron regulated basic helix-loop-helix protein involved in Fe homeostasis in Oryza sativa.
Iron (Fe) is the most limiting micronutrient element for crop production in alkaline soils. A number of transcription factors involved in regulating Fe uptake from soil and transport in plants have been identified. Analysis of transcriptome data from Oryza sativa grown under limiting Fe conditions reveals that transcript abundances of several genes encoding transcription factors are altered by Fe availability. These transcription factors are putative regulators of Fe deficiency responses. Transcript abundance of one nuclear located basic helix-loop-helix family transcription factor, OsIRO3, is up-regulated from 25- to 90-fold under Fe deficiency in both root and shoot respectively. The expression of OsIRO3 is specifically induced by Fe deficiency, and not by other micronutrient deficiencies. Transgenic rice plants over-expressing OsIRO3 were hypersensitive to Fe deficiency, indicating that the Fe deficiency response was compromised. Furthermore, the Fe concentration in shoots of transgenic rice plants over-expressing OsIRO3 was less than that in wild-type plants. Analysis of the transcript abundances of genes normally induced by Fe deficiency in OsIRO3 over-expressing plants indicated their induction was markedly suppressed. A novel Fe regulated bHLH transcription factor (OsIRO3) that plays an important role for Fe homeostasis in rice was identified. The inhibitory effect of OsIRO3 over-expression on Fe deficiency response gene expression combined with hypersensitivity of OsIRO3 over-expression lines to low Fe suggest that OsIRO3 is a negative regulator of the Fe deficiency response in rice.


Comparison of ballistic and static stretching on hamstring muscle length using an equal stretching dose.
The purpose of this investigation was to determine which stretching technique, static or ballistic, is most effective for increasing hamstring muscle length when delivered at the same stretching dose over a 4-week training program. A single-blind, randomized controlled trial design was used in this investigation. Thirty-two participants (16 women and 16 men) between the ages of 18 and 27 years participated in the study. All participants who had a pre-training knee extension angle of less than 20° were excluded from the study. Subjects were randomly assigned to one of 3 groups: ballistic stretching, static stretching, or control group. Participants in the experimental stretching groups (ballistic and static stretching) performed one 30-second stretch 3 times per week for a period of 4 weeks. Statistical analysis consisted of a 2-way analysis of variance (group × sex) with an a priori alpha level of 0.05. No interaction between group and sex was identified (p = 0.4217). The main effect of sex was not statistically significant (p = 0.2099). The main effect for group was statistically significant at p < 0.0001. Post hoc analysis revealed that both static and ballistic stretching group produced greater increases in hamstring length than the control group. The static stretching group demonstrated a statistically greater increase in hamstring muscle length than the ballistic stretching group. No injuries or complications were attributed to either stretching program.


Determinants of mRNA stability in Dictyostelium discoideum amoebae: differences in poly(A) tail length, ribosome loading, and mRNA size cannot account for the heterogeneity of mRNA decay rates.
As an approach to understanding the structures and mechanisms which determine mRNA decay rates, we have cloned and begun to characterize cDNAs which encode mRNAs representative of the stability extremes in the poly(A)+ RNA population of Dictyostelium discoideum amoebae. The cDNA clones were identified in a screening procedure which was based on the occurrence of poly(A) shortening during mRNA aging. mRNA half-lives were determined by hybridization of poly(A)+ RNA, isolated from cells labeled in a 32PO4 pulse-chase, to dots of excess cloned DNA. Individual mRNAs decayed with unique first-order decay rates ranging from 0.9 to 9.6 h, indicating that the complex decay kinetics of total poly(A)+ RNA in D. discoideum amoebae reflect the sum of the decay rates of individual mRNAs. Using specific probes derived from these cDNA clones, we have compared the sizes, extents of ribosome loading, and poly(A) tail lengths of stable, moderately stable, and unstable mRNAs. We found (i) no correlation between mRNA size and decay rate; (ii) no significant difference in the number of ribosomes per unit length of stable versus unstable mRNAs, and (iii) a general inverse relationship between mRNA decay rates and poly(A) tail lengths. Collectively, these observations indicate that mRNA decay in D. discoideum amoebae cannot be explained in terms of random nucleolytic events. The possibility that specific 3'-structural determinants can confer mRNA instability is suggested by a comparison of the labeling and turnover kinetics of different actin mRNAs. A correlation was observed between the steady-state percentage of a given mRNA found in polysomes and its degree of instability; i.e., unstable mRNAs were more efficiently recruited into polysomes than stable mRNAs. Since stable mRNAs are, on average, "older" than unstable mRNAs, this correlation may reflect a translational role for mRNA modifications that change in a time-dependent manner. Our previous studies have demonstrated both a time-dependent shortening and a possible translational role for the 3' poly(A) tracts of mRNA. We suggest, therefore, that the observed differences in the translational efficiency of stable and unstable mRNAs may, in part, be attributable to differences in steady-state poly(A) tail lengths.


Adipose stem cell-based regenerative medicine for reversal of diabetic hyperglycemia.
Diabetes mellitus (diabetes) is a devastating disease that affects millions of people globally and causes a myriad of complications that lead to both patient morbidity and mortality. Currently available therapies, including insulin injection and beta cell replacement through either pancreas or pancreatic islet transplantation, are limited by the availability of organs. Stem cells provide an alternative treatment option for beta cell replacement through selective differentiation of stem cells into cells that recognize glucose and produce and secrete insulin. Embryonic stem cells, albeit pluripotent, face a number of challenges, including ethical and political concerns and potential teratoma formation. Adipose tissue represents an alternative source of multipotent mesenchymal stem cells, which can be obtained using a relatively simple, non-invasive, and inexpensive method. Similarly to other adult mesenchymal stem cells, adipose-derived stem cells (ADSCs) are capable of differentiating into insulin-producing cells. They are also capable of vasculogenesis and angiogenesis, which facilitate engraftment of donor pancreatic islets when co-transplanted. Additionally, anti-inflammatory and immunomodulatory effects of ADSCs can protect donor islets during the early phase of transplantation and subsequently improve engraftment of donor islets into the recipient organ. Although ADSC-therapy is still in its infancy, the potential benefits of ADSCs are far reaching.


Effects of dietary combination of n-3 and n-9 fatty acids on the deposition of linoleic and arachidonic acid in broiler chicken meats.
To minimize the amount of n-6 fatty acids in broiler chicken meat, 120 Cobb × Ross male broilers were divided into 6 different groups and fed a basal corn-soybean meal diet containing 5% fat from 5 different lipid sources: 1) a commercial mix of animal and vegetable oil, 2) soybean oil and olive oil (2.5% each), 3) flaxseed oil and olive oil (2.5% each), 4) flaxseed oil, eicosapentaenoic acid (C20:5; EPA; n-3), and olive oil (2.45, 0.05, and 2.5% respectively; FEO), 5) flaxseed oil, docosahexaenoic acid (C22:6; DHA; n-3), and olive oil (2.45, 0.05, and 2.5% respectively; FDO), and 6) fish oil and olive oil (2.5% each; FHO). At 6 and 9 wk, one bird per pen (4 pens per treatment) was processed, and liver, breast, and thigh samples were collected and used for fatty acid profiles or Δ6- and Δ9-desaturase mRNA gene expression levels. The deposition of linoleic acid (C18:2; n-6) or arachidonic acid (C20:4; n-6) was decreased in breast and thigh muscles of chickens fed n-3 fatty acids for 9 wk compared with chickens fed animal and vegetable oil and soybean oil and olive oil diets (P < 0.05). The addition of EPA to the diet (FEO; P > 0.05) did not reduce the deposition of linoleic acid and arachidonic acid as much as DHA (FDO; P < 0.05), and it suppressed the expression of Δ6- and Δ9-desaturase. When EPA and DHA were blended (FHO) and supplied to broiler chickens for 9 wk, EPA and DHA combination effects were observed on the deposition of LA and arachidonic acid in breast and thigh muscles. Thereby, the addition of a mixed EPA and DHA to a broiler chicken diet may be recommendable to reduce arachidonic acid accumulation in both broiler chicken breast and thigh meats, providing a functional broiler chicken meat to consumers.


Protein co-isolated with human tissue factor impairs recovery of activity.
Preparations of human tissue factor isolated by immunoaffinity chromatography contain variable amounts of 47,000 mol wt, 55,000 mol wt, and multimeric tissue factor when analyzed without reduction on polyacrylamide gels in sodium dodecyl sulfate (SDS). When analyzed after reduction, the 47,000 mol wt tissue factor apoprotein and a protein of about 12,000 mol wt are observed. Elution of tissue factor from polyacrylamide gel slices, followed by reassociation with lipids, restored proportionately much greater tissue factor activity with the 47,000-mol wt protein than with the 55,000-mol wt form. Cyanogen bromide cleavage at the single tissue factor methionine revealed that the 12,000-mol wt protein is associated with the carboxyl-terminal peptide derived from the 47,000-mol wt protein. These results reveal that association of the 12,000-mol wt protein with the cytoplasmic domain of tissue factor can modulate its activity in vitro.


International codes and agreements to restrict the promotion of harmful products can hold lessons for the control of alcohol marketing.
Background and aims The 2011 UN Summit on Non-Communicable Disease failed to call for global action on alcohol marketing despite calls in the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases 2013-20 to restrict or ban alcohol advertising. In this paper we ask what it might take to match the global approach to tobacco enshrined in the Framework Convention on Tobacco Control (FCTC), and suggest that public health advocates can learn from the development of the FCTC and the Code of Marketing on infant formula milks and the recent recommendations on restricting food marketing to children. Methods Narrative review of qualitative accounts of the processes that created and monitor existing codes and treaties to restrict the marketing of consumer products, specifically breast milk substitutes, unhealthy foods and tobacco. Findings The development of treaties and codes for market restrictions include: (i) evidence of a public health crisis; (ii) the cost of inaction; (iii) civil society advocacy; (iv) the building of capacity; (v) the management of conflicting interests in policy development; and (vi) the need to consider monitoring and accountability to ensure compliance. Conclusion International public health treaties and codes provide an umbrella under which national governments can strengthen their own legislation, assisted by technical support from international agencies and non-governmental organizations. Three examples of international agreements, those for breast milk substitutes, unhealthy foods and tobacco, can provide lessons for the public health community to make progress on alcohol controls. Lessons include stronger alliances of advocates and health professionals and better tools and capacity to monitor and report current marketing practices and trends.


The Effects of On-Field Heat Index and Altitude on Concussion Assessments and Recovery Among NCAA Athletes.
Recent literature has indicated altitude may be a protective factor for concussion but it is unknown whether altitude or heat index affects recovery. To examine whether on-field heat index and altitude at the time of injury alter acute (< 48 h) concussion assessments, days-to-asymptomatic, and days-to-return-to-play in collegiate athletes following concussion. Collegiate athletes (n = 187; age = 19.7 ± 1.4 years; male = 70.6%) underwent baseline assessments across 30 universities and experienced a concussion in this retrospective cohort study. Altitude (m) and heat index (°C) at the time and location of injury were determined using valid online database tools. Acute concussion assessments included the Sport Concussion Assessment Tool (SCAT) symptom inventory, Balance Error Scoring System (BESS), and the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). We used multiple linear regression models to determine whether heat index and altitude predicted each acute assessment outcome, days-to-asymptomatic, and days-to-return-to-play. Collegiate athletes were concussed at a 181.1 m (range - 0.6 to 2201.9 m) median altitude and 17.8 °C (range - 6.1 to 35.6 °C) median heat index. Altitude did not predict (p ≥ 0.265) any outcomes. Every one-degree increase in heat index reduced days-to-asymptomatic (p = 0.047; R2 = 0.06) and days-to-return-to-play (p = 0.006; R2 = 0.09) by 0.05 and 0.14 days, respectively. Heat index and altitude did not explain significant variance in SCAT, BESS, and ImPACT composite scores (p's = 0.20-0.922). Our findings suggest that on-field altitude and heat index at the time of injury do not contribute to clinically meaningful changes on acute assessments or concussion recovery. On-field altitude and heat index do not appear to significantly alter assessment outcomes or clinical recovery, suggesting that environmental factors at altitudes below < 2500 m are negligible outcomes for researchers and clinicians to consider post-concussion.


Dental behavioural management problems and dental caries prevalence in 3- to 6-year-old Swedish children born preterm.
Today, most children born preterm survive without major impairments. But high frequencies of cognitive and behavioural difficulties arise. Studies on dental behavioural management problems (DBMP) in these children are lacking. In addition, studies on caries prevalence are few and inconclusive. This study aims to compare the frequency of behavioural problems and poor compliance with dental treatment in preschool children born preterm with those born full-term. The prevalence of caries was also studied. The study group included 187 children born between 23 and 32 weeks of gestation. The control group constituted full-term children matched by age, sex, immigrant background, and dental operator. DBMP, number of dental visits, missed appointments, and caries between ages 3 and 6 were noted. At age 3, but not at age 6, the prevalence of DBMP at clinical examinations was significantly higher in preterm children compared with the control group. Of the children who received dental treatments during preschool years, preterm children displayed significantly more DBMP. No significant difference in dental visits or in caries prevalence was found. Preterm children, however, missed significantly more dental appointments. Children born preterm display a higher prevalence of DBMP at dental examinations and treatments during preschool years.