Genetic deletion of the p66Shc adaptor protein protects from angiotensin II-induced myocardial damage.
Angiotensin II (Ang II), acting through its G protein-coupled AT1 receptor (AT1), contributes to the precocious heart senescence typical of patients with hypertension, atherosclerosis, and diabetes. AT1 was suggested to transactivate an intracellular signaling controlled by growth factors and their tyrosin-kinase receptors. In cultured vascular smooth muscle cells, this downstream mechanism comprises the p66Shc adaptor protein, previously recognized to play a role in vascular cell senescence and death. The aim of the present study was 2-fold: (1) to characterize the cardiovascular phenotype of p66Shc knockout mice (p66Shc(-/-)), and (2) to test the novel hypothesis that disrupting the p66Shc might protect the heart from the damaging action of elevated Ang II levels. Compared with wild-type littermates (p66Shc(+/+)), p66Shc(-/-) showed similar blood pressure, heart rate, and left ventricular wall thickness. However, cardiomyocyte number was increased in mutant animals, indicating a condition of myocardial hyperplasia. In p66Shc(+/+), infusion of a sub-pressor dose of Ang II (300 nmol/kg body weight [BW] daily for 28 days) caused left ventricular hypertrophy and apoptotic death of cardiomyocytes and endothelial cells. In contrast, p66Shc(-/-) were resistant to the proapoptotic/hypertrophic action of Ang II. Consistently, in vitro experiments showed that Ang II causes apoptotic death of cardiomyocytes isolated from p66Shc(+/+) hearts to a greater extent as compared with p66Shc(-/-) cardiomyocytes. Our results indicate a fundamental role of p66Shc in Ang II-mediated myocardial remodeling. In perspective, p66Shc inhibition may be envisioned as a novel way to prevent the deleterious effects of Ang II on the heart.


Improving COVID-19 CT classification of CNNs by learning parameter-efficient representation.
The COVID-19 pandemic continues to spread rapidly over the world and causes a tremendous crisis in global human health and the economy. Its early detection and diagnosis are crucial for controlling the further spread. Many deep learning-based methods have been proposed to assist clinicians in automatic COVID-19 diagnosis based on computed tomography imaging. However, challenges still remain, including low data diversity in existing datasets, and unsatisfied detection resulting from insufficient accuracy and sensitivity of deep learning models. To enhance the data diversity, we design augmentation techniques of incremental levels and apply them to the largest open-access benchmark dataset, COVIDx CT-2A. Meanwhile, similarity regularization (SR) derived from contrastive learning is proposed in this study to enable CNNs to learn more parameter-efficient representations, thus improve the accuracy and sensitivity of CNNs. The results on seven commonly used CNNs demonstrate that CNN performance can be improved stably through applying the designed augmentation and SR techniques. In particular, DenseNet121 with SR achieves an average test accuracy of 99.44% in three trials for three-category classification, including normal, non-COVID-19 pneumonia, and COVID-19 pneumonia. The achieved precision, sensitivity, and specificity for the COVID-19 pneumonia category are 98.40%, 99.59%, and 99.50%, respectively. These statistics suggest that our method has surpassed the existing state-of-the-art methods on the COVIDx CT-2A dataset. Source code is available at https://github.com/YujiaKCL/COVID-CT-Similarity-Regularization.


Presentation by a major histocompatibility complex class I molecule of nucleoprotein peptide expressed in two different genes of an influenza virus transfectant.
Major histocompatibility (MHC) class I glycoproteins are specialized to present to CD8+ T cells, peptides that originate from proteins synthesized within the cytoplasm. Conventional killed vaccines are unable to get into the cell cytoplasm and therefore fail to expand the CD8+ T cell population. We have created a novel influenza transfectant virus, R10, which carries an immunogenic peptide from the nucleoprotein (NP) of PR8 influenza virus in its hemagglutinin (HA) and another similar peptide in its HK influenza virus NP. The two peptides are both presented by H-2Db and bind with approximately equal affinity. They can compete with one another for binding to H-2Db. Yet in cells infected with R10, both peptides are presented efficiently enough to expand the respective cytotoxic T lymphocyte (CTL) precursors in vivo and to serve as targets for CTL lysis in vitro. It has been proposed that proteins bearing signal sequences may be processed by a transporter-independent pathway. To investigate this, we infected the transporter-deficient cell line RMA-S with the R10 virus to see if the NP peptide expressed by the HA would be presented. The result shows that even the presence of a signal peptide in the HA does not overcome the lack of a transporter function, suggesting that the presentation of both peptides is dependent on functional transporter proteins. Our data also suggest the feasibility of creating by genetic engineering, recombinant vaccines expressing multiple epitopes that can effectively stimulate a cellular immune response.


Feeding a city - Leicester as a case study of the importance of allotments for horticultural production in the UK.
The process of urbanization has detached a large proportion of the global population from involvement with food production. However, there has been a resurgence in interest in urban agriculture and there is widespread recognition by policy-makers of its potential contribution to food security. Despite this, there is little data on urban agricultural production by non-commercial small-scale growers. We combine citizen science data for self-provisioning crop yields with field-mapping and GIS-based analysis of allotments in Leicester, UK, to provide an estimate of allotment fruit and vegetable production at a city-scale. In addition, we examine city-scale changes in allotment land provision on potential crop production over the past century. The average area of individual allotment plots used to grow crops was 52%. Per unit area yields for the majority of crops grown in allotments were similar to those of UK commercial horticulture. We estimate city-wide allotment production of >1200 t of fruit and vegetables and 200 t of potatoes per annum, equivalent to feeding >8500 people. If the 13% of plots that are completely uncultivated were used this could increase production to >1400 t per annum, feeding ~10,000 people, however this production may not be located in areas where there is greatest need for increased access to fresh fruits and vegetables. The citywide contribution of allotment cultivation peaked in the 1950s when 475 ha of land was allotments, compared to 97 ha currently. This suggests a decline from >45,000 to <10,000 of people fed per annum. We demonstrate that urban allotments make a small but important contribution to the fruit and vegetable diet of a UK city. However, further urban population expansion will exert increasing development pressure on allotment land. Policy-makers should both protect allotments within cities, and embed urban agricultural land within future developments to improve local food security.


The mGluR2 Positive Allosteric Modulator, AZD8529, and Cue-Induced Relapse to Alcohol Seeking in Rats.
Group II metabotropic glutamate receptors (mGluR2 and mGluR3) may control relapse of alcohol seeking, but previously available Group II agonists were unable to discriminate between mGluR2 and mGluR3. Here we use AZD8529, a novel positive allosteric mGluR2 modulator, to determine the role of this receptor for alcohol-related behaviors in rats. We assessed the effects of AZD8529 (20 and 40 mg/kg s.c.) on male Wistar rats trained to self-administer 20% alcohol and determined the effects of AZD8529 on self-administration, as well as stress-induced and cue-induced reinstatement of alcohol seeking. The on-target nature of findings was evaluated in Indiana P-rats, a line recently shown to carry a mutation that disrupts the gene encoding mGluR2. The behavioral specificity of AZD8529 was assessed using self-administration of 0.2% saccharin and locomotor activity tests. AZD8529 marginally decreased alcohol self-administration at doses that neither affected 0.2% saccharin self-administration nor locomotor activity. More importantly, cue- but not stress-induced alcohol seeking was blocked by the mGluR2 positive allosteric modulator. This effect of AZD8529 was completely absent in P rats lacking functional mGluR2s, demonstrating the receptor specificity of this effect. Our findings provide evidence for a causal role of mGluR2 in cue-induced relapse to alcohol seeking. They contribute support for the notion that positive allosteric modulators of mGluR2 block relapse-like behavior across different drug categories.


Species and genotypic diversities and similarities of pathogenic yeasts colonizing women.
We examined the patterns of strain relatedness among pathogenic yeasts from within and among groups of women to determine whether there were significant associations between genotype and host condition or body site. A total of 80 yeast strains were isolated, identified, and genotyped from 49 female volunteers, who were placed in three groups: (i) 19 women with AIDS, (ii) 11 pregnant women without human immunodeficiency virus (HIV) infection, and (iii) 19 women who were neither pregnant nor infected with HIV. Seven yeast species were recovered, including 59 isolates of Candida albicans, 9 isolates of Candida parapsilosis, 5 isolates of Candida krusei, 3 isolates of Candida glabrata, 2 isolates of Saccharomyces cerevisiae, and 1 isolate each of Candida tropicalis and Candida lusitaniae. Seventy unique genotypes were identified by PCR fingerprinting with the M13 core sequence and by random amplified polymorphic DNA analysis. Of the nine shared genotypes, isolates from three different hosts were of one genotype and pairs of strains from different body sites of the same host shared each of the other eight genotypes. Genetic similarities among groups of strains were calculated and compared. We found no significant difference in the patterns of relatedness of strains from the three body sites (oral cavity, vagina, and rectum), regardless of host conditions. The yeast microflora of all three host groups had similar species and genotypic diversities. Furthermore, a single host can be colonized with multiple species or multiple genotypes of the same species at the same or different body sites, indicating dynamic processes of yeast colonization on women.


Meta-analysis of genome-wide association studies for circulating phylloquinone concentrations.
Poor vitamin K status is linked to greater risk of several chronic diseases. Age, sex, and diet are determinants of circulating vitamin K; however, there is still large unexplained interindividual variability in vitamin K status. Although a strong genetic component has been hypothesized, this has yet to be examined by a genome-wide association (GWA) study. The objective was to identify common genetic variants associated with concentrations of circulating phylloquinone, the primary circulating form of vitamin K. We conducted a 2-stage GWA meta-analysis of circulating phylloquinone in 2 populations of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Nutrition Working Group. Circulating phylloquinone was measured by using reversed-phase high-performance liquid chromatography. Results from adjusted cohort-specific discovery GWA analyses were meta-analyzed with inverse variance weights (n = 2138). Associations with circulating phylloquinone at P < 1 × 10(-6) were then evaluated in a second-stage analysis consisting of one independent cohort (n = 265). No significant association was observed for circulating phylloquinone at the genome-wide significance level of 5 × 10(-8). However, from the discovery GWA, there were 11 single-nucleotide polymorphism (SNP) associations with circulating phylloquinone at P < 1 × 10(-6), including a functional variant previously associated with warfarin dose and altered phylloquinone metabolism. These SNPs are on 5 independent loci on 11q23.3, 8q24.3, 5q22.3, 2p12, and 19p13.12, and they fall within or near the candidate genes APOA1/C3/A4/A5 cluster (involved in lipoprotein metabolism), COL22A1, CDO1, CTNAA2, and CYP4F2 (a phylloquinone oxidase), respectively. Second-stage analysis in an independent cohort further suggests the association of the 5q22.3 locus with circulating phylloquinone (P < 0.05). Multiple candidate genes related to lipoprotein and vitamin K metabolism were identified as potential determinants of circulating phylloquinone. Further investigation with a larger sample is warranted to verify our initial findings and identify other loci contributing to circulating phylloquinone. Trials related to this study were registered at clinicaltrials.gov as NCT00005121 (Framingham Offspring Study) and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).


Multidimensional Analyses Reveal Unequal Resource, Economic, and Environmental Gains and Losses among the Global Aluminum Trade Leaders.
Disputes around trade inequality have been growing over the last 2 decades, with different countries claiming inequality in different terms including monetary deficits, resource appropriation and degradation, and environmental emission transfer. Despite prior input-output-based studies analyzing multidimensional trade consequences at the sector level, there is a lack of bottom-up studies that uncover the complexity of trade imbalances at the product level. This paper quantifies four types of flows, monetary, resource, embodied energy use, and embodied greenhouse gas (GHG) emissions, resulting from aluminum trade for the four economies with the highest aluminum trade, that is, the United States, China, Japan, and Australia. Results show that the United States has a negative balance in monetary flows but a positive balance in resource flows, embodied energy use, and GHG emissions. China has a positive balance in monetary and resource flows but a negative balance in embodied energy use and GHG emissions. Japan has a positive balance in all flows, while Australia has a negative balance in all flows. These heterogeneous gains and losses along the global leaders of aluminum trade arise largely from their different trade structures and the heterogeneities of price, energy use, and GHG emission intensities of aluminum products; for example, Japan mainly imports unwrought aluminum, and its quantity is 3 times that of the exported semis and finished aluminum-containing products that have similar energy and GHG emission intensities but 20 times higher prices, while Australia mainly exports bauxite and alumina that have the lowest prices, the quantity of which is 25 times that of imported semis and finished products. This study suggests that resource-related trade inequalities are not uniform across economic and environmental impacts and that trade policies must be carefully considered from various dimensions.


Effect of scapular stabilization exercise on neck alignment and muscle activity in patients with forward head posture.
[Purpose] The purpose of this study was to investigate the effects of scapula movement on neck alignment and the muscles in patients with forward head posture, who has the structural changes around the neck caused from the forward head posture, when scapular stabilization exercise is applied. [Subjects and Methods] A sample of 30 patients with forward head posture were recruited and participated in an intervention for 30 minutes a day, three times per week for 4 weeks. Fifteen patients were assigned to the scapular stabilization exercise group and the remaining 15 were assigned to the neck stabilization exercise group. Before the intervention, the craniovertebral angle (CVA), cranial rotation angle (CRA), and muscle activity of the muscles around the neck were measured. Four weeks later, these 3 factors were re-measured and analyzed. [Results] Within-group changes in CVA and CRA were observed in both groups and were statistically significant. Only the CVA group had a statistically significant between-group differences. Within-group changes in muscular activity were significant differences in all groups. Between groups, the lower back trapezius and serratus anterior showed statistically significant differences. [Conclusion] Scapular stabilization brought about improvement in posture through activation of the neck muscles, the lower trapezius, and the serratus anterior. Therefore, the intervention has a positive effect on neck alignment by reducing the compensatory movements of the muscles involved in forward head posture. Structural changes are observed.


Transcriptional analysis of the major antigenic protein 1 multigene family of Cowdria ruminantium.
The major antigenic protein 1 (MAP1) of the tick-borne rickettsial pathogen Cowdria ruminantium is encoded by a multigene family containing conserved and variable genes. The part of a locus containing the map1 multigene family that was characterized contained three homologous, but non-identical map1 genes, designated map1-2, map1-1, and map1. Reverse transcriptase-polymerase chain reaction was used to study the transcriptional activity of these genes in isolates of C. ruminantium grown in bovine endothelial cells, in two different tick cell lines, and in Amblyomma variegatum ticks. The map1 gene was always transcribed, whereas transcription of map1-2 was not detected under any of the tested conditions. The map1-1 gene transcript was detected in A. variegatum ticks, but was not found in virulent C. ruminantium Senegal grown in bovine endothelial cells at 30 or 37 degrees C. Interestingly, transcripts of map1-1 were also found in different passages of the in vitro attenuated Senegal isolate grown in bovine endothelial cells, as well as in the Gardel isolate grown in two tick cell lines. When transcribed, map1-1 was present on a polycistronic messenger together with map1.


Development, reliability, and validity of the Handwriting Proficiency Screening Questionnaire (HPSQ).
This study was used to (1) develop an occupational therapy screening questionnaire (the Handwriting Proficiency Screening Questionnaire [HPSQ]) to identify handwriting difficulties among school-aged children and (2) examine its reliability and validity. The questionnaire's content validity was established. Internal consistency, interrater and test-retest reliability, and concurrent and construct validity were initiated. Participants included 7- to 14-year-old (N = 230) typically developing school-aged children. The tool demonstrated good internal consistency (alpha = .90). Test-retest reliability for the score revealed an intraclass correlation coefficient (ICC) of .84 and interrater reliability of ICC = .92 for the total questionnaire score. Construct and concurrent validity were also confirmed. The HPSQ is suitable for use by occupational therapists for identification of handwriting deficiency among school-aged children and is appropriate for varied academic and clinical uses. More studies with larger samples of varied age groups are required to further support the questionnaire's reliability and validity.


Behavioural analyses of quinine processing in choice, feeding and learning of larval Drosophila.
Gustatory stimuli can support both immediate reflexive behaviour, such as choice and feeding, and can drive internal reinforcement in associative learning. For larval Drosophila, we here provide a first systematic behavioural analysis of these functions with respect to quinine as a study case of a substance which humans report as "tasting bitter". We describe the dose-effect functions for these different kinds of behaviour and find that a half-maximal effect of quinine to suppress feeding needs substantially higher quinine concentrations (2.0 mM) than is the case for internal reinforcement (0.6 mM). Interestingly, in previous studies (Niewalda et al. 2008, Schipanski et al 2008) we had found the reverse for sodium chloride and fructose/sucrose, such that dose-effect functions for those tastants were shifted towards lower concentrations for feeding as compared to reinforcement, arguing that the differences in dose-effect function between these behaviours do not reflect artefacts of the types of assay used. The current results regarding quinine thus provide a starting point to investigate how the gustatory system is organized on the cellular and/or molecular level to result in different behavioural tuning curves towards a bitter tastant.


GLAD: an Online Database of Gene List Annotation for Drosophila.
We present a resource of high quality lists of functionally related Drosophila genes, e.g. based on protein domains (kinases, transcription factors, etc.) or cellular function (e.g. autophagy, signal transduction). To establish these lists, we relied on different inputs, including curation from databases or the literature and mapping from other species. Moreover, as an added curation and quality control step, we asked experts in relevant fields to review many of the lists. The resource is available online for scientists to search and view, and is editable based on community input. Annotation of gene groups is an ongoing effort and scientific need will typically drive decisions regarding which gene lists to pursue. We anticipate that the number of lists will increase over time; that the composition of some lists will grow and/or change over time as new information becomes available; and that the lists will benefit the scientific community, e.g. at experimental design and data analysis stages. Based on this, we present an easily updatable online database, available at www.flyrnai.org/glad, at which gene group lists can be viewed, searched and downloaded.


Proliferation and multilineage potential of CXCR4-positive human dental pulp cells in vitro.
Although the results of our previous studies showed that the stromal cell-derived factor (SDF)-1α-CXC chemokine receptor 4 (CXCR4) axis may play a role in the recruitment of CXCR4-positive dental pulp cells (CXCR4(+) DPCs) toward the damaged sites, the specific function of CXCR4(+) DPCs in the injured dental pulp was still unknown. The purpose of this study was to verify whether CXCR4(+) DPCs possessed stem cells properties so that we can understand their role in area of injury. CXCR4(+) DPCs were isolated from normal DPCs with magnetic-activated cell sorting. The characteristics of the cells from the 3 groups of cells (ie, CXCR4(+) DPCs, CXCR4(-) DPCs, or nonsorted DPCs) were analyzed in colony formation, proliferation, and multilineage differentiation including odontogenic and adipogenic lineages. The results showed that CXCR4(+) DPCs were the most dominant population in colony formation, proliferation, alkaline phosphatase activity, calcium content, and adipogenic differentiation among the 3 groups. CXCR4(+) DPCs may contain more stem cells than nonsorted DPCs.


Cryo-electron microscopy of extracellular vesicles in fresh plasma.
Extracellular vesicles (EV) are phospholipid bilayer-enclosed vesicles recognized as new mediators in intercellular communication and potential biomarkers of disease. They are found in many body fluids and mainly studied in fractions isolated from blood plasma in view of their potential in medicine. Due to the limitations of available analytical methods, morphological information on EV in fresh plasma is still rather limited. To image EV and determine the morphology, structure and size distribution in fresh plasma by cryo-electron microscopy (cryo-EM). Fresh citrate- and ethylenediaminetetraacetic acid (EDTA)-anticoagulated plasma or EV isolated from these plasmas were rapidly cryo-immobilized by vitrification and visualized by cryo-EM. EV isolated from fresh plasma were highly heterogeneous in morphology and size and mostly contain a discernible lipid bilayer (lipid vesicles). In fresh plasma there were 2 types of particles with a median diameter of 30 nm (25-260 nm). The majority of these particles are electron dense particles which most likely represent lipoproteins. The minority are lipid vesicles, either electron dense or electron lucent, which most likely represent EV. Lipid vesicles were occasionally observed in close proximity of platelets in citrate and EDTA-anticoagulated platelet-rich plasma. Cryo-electron tomography (cryo-ET) was employed to determine the 3D structure of platelet secretory granules. Cryo-EM is a powerful technique that enables the characterization of EV in fresh plasma revealing structural details and considerable morphological heterogeneity. Only a small proportion of the submicron structures in fresh plasma are lipid vesicles representing EV.


Detection and differentiation of antigenically distinct small round-structured viruses (Norwalk-like viruses) by reverse transcription-PCR and southern hybridization.
Application of reverse transcription (RT)-PCR to detect small round-structured viruses (SRSVs) from fecal specimens of patients with gastroenteritis has been insensitive because of the tremendous sequence heterogeneity between strains. We have designed two RT-PCR primer sets (G-1 and G-2) based on the nucleotide sequence diversity in the RNA polymerase gene of SRSVs belonging to two distinct genogroups represented by Norwalk virus (primers G-1) and Snow Mountain agent (primers G-2). All 22 SRSV strains examined that had been classified previously by solid-phase immune electron microscopy into four antigenic types (UK1, UK2, UK3, and UK4) could be detected by RT-PCR with these two primer sets. The G-1 primer set detected 6 UK2 strains, and the G-2 primers detected 16 strains, including 7 UK1, 5 UK3, and 4 UK4 strains. On the basis of nucleotide sequences of 81-bp fragments of the RT-PCR products from 13 strains determined in this study, together with those previously reported for 17 SRSV strains, we designed four sets of internal oligonucleotide probes (P1-A, P1-B, P2-A, and P2-B) for Southern hybridization, using chemiluminescent detection. The P1-A probe hybridized with PCR products from the UK2 strains; the P1-B probe, with products from two of the seven UK1 strains; the P2-A probe, with four of the remaining five UK1 strains; and the P2-B probe, with products from both UK3 and UK4 strains, as well as with one strain originally typed as UK1 which showed cross-reactivity with UK4 upon retesting by solid-phase immune electron microscopy. RT-PCR with both the G-1 and the G-2 primer sets can increase the detection rate of the many antigenically distinct SRSVs and, when combined with Southern hybridization, may predict the antigenic type of the SRSV associated with infection.


Shack-Hartmann mask/pupil registration algorithm for wavefront sensing in segmented mirror telescopes.
Shack-Hartmann wavefront sensing in general requires careful registration of the reimaged telescope primary mirror to the Shack-Hartmann mask or lenslet array. The registration requirements are particularly demanding for applications in which segmented mirrors are phased using a physical optics generalization of the Shack-Hartmann test. In such cases the registration tolerances are less than 0.1% of the diameter of the primary mirror. We present a pupil registration algorithm suitable for such high accuracy applications that is based on the one used successfully for phasing the segments of the Keck telescopes. The pupil is aligned in four degrees of freedom (translations, rotation, and magnification) by balancing the intensities of subimages formed by small subapertures that straddle the periphery of the mirror. We describe the algorithm in general terms and then in the specific context of two very different geometries: the 492 segment Thirty Meter Telescope, and the seven "segment" Giant Magellan Telescope. Through detailed simulations we explore the accuracy of the algorithm and its sensitivity to such effects as cross talk, noise/counting statistics, atmospheric scintillation, and segment reflectivity variations.


Aesthetics in Thyroid Surgery: The Patient Perspective.
Objectives To define characteristics that influence patient perceptions of thyroidectomy scar cosmesis. Study Design Prospective cohort study. Setting Tertiary endocrine surgery practice in an academic medical center. Subjects and Methods Institutional review board-approved trial in which 136 subjects were recruited from a population of patients being seen for either thyroid or sinus surgery and evaluated standardized photographs, superimposed with computer-generated thyroidectomy scars of varying lengths (2, 4, and 6 cm) and widths (1 and 2 mm), and graded their perception of the scars using the observer scar assessment scale (OSAS) domains of the patient and observer scar assessment scale. Results There were 69 subjects in the thyroid group and 67 in the nonthyroid group. Controlling for width, longer scars were perceived as worse than shorter scars; controlling for length, thicker scars were perceived as worse than thinner scars ( P < .01). Beyond 2 cm, thick scars were judged to be worse than thin scars, even when they were shorter. There was no difference in the mean overall OSAS scores between surgery, sex, or age groups. Nonwhites tended to judge scars as being worse than whites did ( P < .01). Conclusion As expected, patients of all demographics prefer shorter scars compared with longer scars and thinner scars over thick scars. Ethnic differences in scar perception were identified and deserve additional study. Surgeons should endeavor to perform thyroid surgery through the smallest incision that allows the operation to be performed safely to minimize the cosmetic impact of the operation.


Safety and efficacy of an additive consisting of Bacillus subtilis DSM 32324 for all animal species (Chr. Hansen A/S).
Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the additive consisting of Bacillus subtilis DSM 32324 when used as a technological additive (hygiene condition enhancer) in feed for all animal species. The product is intended for use in dry feeds at a minimum inclusion level of 1 × 108 colony forming unit (CFU)/kg complete feedingstuff. The bacterial species Bacillus subtilis DSM 32324 is considered by EFSA to be eligible for the qualified presumption of safety approach. As the identity of the strain has been clearly established and it did not show acquired resistance to antibiotics of human and veterinary importance, the use of the strain in animal nutrition is considered safe for the target species, consumers and the environment. No conclusions can be drawn on the skin/eye irritancy or skin sensitisation potential of the product. Exposure of users by inhalation is likely and the product should be considered a respiratory sensitiser. The Panel is not in the position to conclude on the efficacy of Bacillus subtilis DSM 32324 when used in animal nutrition as hygiene condition enhancer due to lack of data. Bacillus subtilis DSM 32324 is compatible with diclazuril, decoquinate and halofuginone. The data provided do not allow to conclude on the compatibility of the additive with monensin sodium, salinomycin sodium, narasin, robenidine hydrochloride and maduramicin ammonium.


Statistical testing in transcriptomic-neuroimaging studies: A how-to and evaluation of methods assessing spatial and gene specificity.
Multiscale integration of gene transcriptomic and neuroimaging data is becoming a widely used approach for exploring the molecular underpinnings of large-scale brain organization in health and disease. Proper statistical evaluation of determined associations between imaging-based phenotypic and transcriptomic data is key in these explorations, in particular to establish whether observed associations exceed "chance level" of random, nonspecific effects. Recent approaches have shown the importance of statistical models that can correct for spatial autocorrelation effects in the data to avoid inflation of reported statistics. Here, we discuss the need for examination of a second category of statistical models in transcriptomic-neuroimaging analyses, namely those that can provide "gene specificity." By means of a couple of simple examples of commonly performed transcriptomic-neuroimaging analyses, we illustrate some of the potentials and challenges of transcriptomic-imaging analyses, showing that providing gene specificity on observed transcriptomic-neuroimaging effects is of high importance to avoid reports of nonspecific effects. Through means of simulations we show that the rate of reported nonspecific effects (i.e., effects that cannot be specifically linked to a specific gene or gene-set) can run as high as 60%, with only less than 5% of transcriptomic-neuroimaging associations observed through ordinary linear regression analyses showing both spatial and gene specificity. We provide a discussion, a tutorial, and an easy-to-use toolbox for the different options of null models in transcriptomic-neuroimaging analyses.


Tinnitus and hearing in 7-year-old children.
Tinnitus occurs with or without prior noise exposure (noise-induced tinnitus (NIT) and spontaneous tinnitus (ST)), and is considered a symptom related to permanent hearing impairment (HI) or temporary hearing threshold shift (TTS). To carry out a cross-sectional interview study on TTS, ST and NIT during a standard audiometric screening of 756 7-year-old children in Gothenburg. 41% out of 756 children reported either NIT or ST on several occasions, 17% reported recurrent TTS and 7% failed the audiometry screening. The probability of ST was 27% for children with no HI or TTS (OR=1.23 (95% CI 1.12 to 1.34)) but 63% (OR=1.16 (95% CI 1.02 to 1.33)) if exhibiting both HI and TTS. This study confirms an increased occurrence of spontaneous tinnitus in children with TTS or HI and in children with both TTS and HI, in particular, but also in children with normal hearing. Possibly, tinnitus in young children correlates with stress as in adolescents and adults.


Symbiosis-induced cascade regulation of the Mesorhizobium loti R7A VirB/D4 type IV secretion system.
The Mesorhizobium loti R7A symbiosis island contains genes encoding a VirB/D4 type IV secretion system (T4SS) similar to that of Agrobacterium tumefaciens. This system has host-dependent effects on symbiosis that probably are due to translocation of two effector proteins, Msi059 and Msi061, into host cells. Here we report that, as in A. tumefaciens, the M. loti vir genes are transcriptionally regulated by a VirA/VirG two-component regulatory system. A virGN54D mutant gene of M. loti caused constitutive expression of lacZ reporter gene fusions to virB1, virD4, msi059, and msi061. Expression of these gene fusions also was activated by a NodD gene product from Rhizobium leguminosarum in the presence of the inducer naringenin, as was a virA::lacZ fusion. This activation was dependent on a nod box present 851 bp upstream of virA, and a mutant with the nod box deleted formed effective nodules on Leucaena leucocephala, the same symbiotic phenotype as other M. loti vir mutants. In contrast, the wild-type strain formed small, empty nodules whereas a nodD1 mutant was completely Nod-. These results indicate that the M. loti vir genes are induced in a symbiosis-specific manner that involves a two-tiered regulatory cascade, and that the vir effectors act after Nod factor during infection thread formation.


Estimate of the energy value of soybean meal relative to corn based on growth performance of nursery pigs.
Two experiments were conducted to determine the effects of increasing amounts of soybean meal (SBM) in swine diets and estimate the energy value of SBM. A total of 2233 pigs (PIC 337 × 1050, Hendersonville, TN) and 3796 pigs (PIC 359 × C40), initially 11.0 kg and 17.6 kg body weight (BW), were used in Exp. 1 and 2, respectively. In Exp. 1, pigs were placed in 92 pens each containing 20 to 27 pigs. In Exp. 2, pigs were placed in 84 pens each containing 37 to 43 pigs. Treatments were assigned in a randomized complete block design with BW as the blocking factor. Dietary treatments consisted of 21%, 27%, 33%, or 39% SBM in Exp. 1 and 17.5%, 22%, 26.5%, 31%, 35.5%, or 40% SBM in Exp. 2, obtained by changing the inclusion rate of feed-grade amino acids and corn grain. For Exp. 1, representative samples of corn grain, SBM, and distillers dried grains with solubles were analyzed for total AA content prior to diet formulation. For Exp. 2, diets were formulated using NRC (2012) nutrient loadings. Treatment diets were fed for 21 and 22 d (Exp. 1 and 2) and there were 23 replicates in Exp. 1 and 14 replicates in Exp. 2. Pigs were weighed and feed disappearance measured weekly to calculate average daily gain (ADG), average daily feed intake (ADFI), gain-to-feed ratio (G:F), and caloric efficiency (CE). Data were analyzed with block as a random effect and treatment as a fixed effect, and contrasts were constructed to test the linear and quadratic effects of increasing SBM. In Exp. 1, there was a tendency (linear, P = 0.092) for a decrease in ADFI as SBM increased. There was a tendency (P = 0.090) for a quadratic response for ADG, with a decrease in ADG observed with 39% SBM inclusion. Pigs fed diets with increasing SBM had a tendency (quadratic, P = 0.069) for an increase in G:F up to 33% SBM and an improvement (linear, P = 0.001; quadratic, P = 0.063) in CE with increasing SBM. Using CE to estimate the energy of SBM relative to corn, a value of 105.4% of corn energy or 2816 kcal/kg NE was determined using all data points. When removing the CE value of the 39% SBM treatment due to the quadratic tendency, SBM was estimated to have 121.1% of corn energy or 3236 kcal/kg NE. In Exp. 2, there was a decrease (linear, P = 0.001) in ADFI. Pigs fed increasing SBM had a tendency (linear, P = 0.065) for reduced ADG but an improvement (linear, P = 0.001) in G:F and CE as SBM increased. The energy value of SBM was estimated as 124.7% of corn energy or 3332 kcal/kg NE. The results suggest that feeding increasing levels of SBM improves G:F and CE. The energy value of SBM was estimated to be between 105% and 125% of corn, which is much greater than the NRC (2012) would indicate.


Occipital alpha activity during stimulus processing gates the information flow to object-selective cortex.
Given the limited processing capabilities of the sensory system, it is essential that attended information is gated to downstream areas, whereas unattended information is blocked. While it has been proposed that alpha band (8-13 Hz) activity serves to route information to downstream regions by inhibiting neuronal processing in task-irrelevant regions, this hypothesis remains untested. Here we investigate how neuronal oscillations detected by electroencephalography in visual areas during working memory encoding serve to gate information reflected in the simultaneously recorded blood-oxygenation-level-dependent (BOLD) signals recorded by functional magnetic resonance imaging in downstream ventral regions. We used a paradigm in which 16 participants were presented with faces and landscapes in the right and left hemifields; one hemifield was attended and the other unattended. We observed that decreased alpha power contralateral to the attended object predicted the BOLD signal representing the attended object in ventral object-selective regions. Furthermore, increased alpha power ipsilateral to the attended object predicted a decrease in the BOLD signal representing the unattended object. We also found that the BOLD signal in the dorsal attention network inversely correlated with visual alpha power. This is the first demonstration, to our knowledge, that oscillations in the alpha band are implicated in the gating of information from the visual cortex to the ventral stream, as reflected in the representationally specific BOLD signal. This link of sensory alpha to downstream activity provides a neurophysiological substrate for the mechanism of selective attention during stimulus processing, which not only boosts the attended information but also suppresses distraction. Although previous studies have shown a relation between the BOLD signal from the dorsal attention network and the alpha band at rest, we demonstrate such a relation during a visuospatial task, indicating that the dorsal attention network exercises top-down control of visual alpha activity.


Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats.
This article describes the relationship between fiber biopersistence and the chronic toxicity of different chemical compositions of man-made vitreous fibers (MMVF) in the lung. Rats were exposed in "nose-only" inhalation chambers, 6 hr/day, 5 days/week, for 24 months to aerosol concentrations of 30 mg/m3 containing comparable fiber numbers and similar dimensions of fibrous glass (FG) or refractory ceramic fiber (RCF). Interim sacrifices were performed periodically to monitor fiber number and dimensions in the lung and the progression of pulmonary alterations. At each interim sacrifice, three to six recovery animals were removed from each exposure group and held until two years to determine the biopersistence of fibers after different exposure times. Fibers were recovered from the ashed lungs, counted, and measured using optical and scanning electron microscopy (SEM). Fiber chemistry was assessed in 91-week recovery lungs using energy dispersive spectroscopy (EDS) analysis. RCF induced lung fibrosis and an elevation in lung tumors and pleural mesotheliomas. FG exposure resulted in no lung fibrosis, no statistically significant increase in the lung tumor incidence, and no mesotheliomas. After two years of continuous exposure, the number of World Health Organization fibers per milligram dry lung recovered from RCF and FG exposed lungs was comparable. EDS analysis of recovery lungs showed that most of the alkalis and alkaline earths had leached from the FG fibers over time. A slight change in RCF chemistry was observed. These findings indicate that the change in the chemical composition of fibers may be an important determinant of the chronic toxicity of MMVFs.


Evolved structure of language shows lineage-specific trends in word-order universals.
Languages vary widely but not without limit. The central goal of linguistics is to describe the diversity of human languages and explain the constraints on that diversity. Generative linguists following Chomsky have claimed that linguistic diversity must be constrained by innate parameters that are set as a child learns a language. In contrast, other linguists following Greenberg have claimed that there are statistical tendencies for co-occurrence of traits reflecting universal systems biases, rather than absolute constraints or parametric variation. Here we use computational phylogenetic methods to address the nature of constraints on linguistic diversity in an evolutionary framework. First, contrary to the generative account of parameter setting, we show that the evolution of only a few word-order features of languages are strongly correlated. Second, contrary to the Greenbergian generalizations, we show that most observed functional dependencies between traits are lineage-specific rather than universal tendencies. These findings support the view that-at least with respect to word order-cultural evolution is the primary factor that determines linguistic structure, with the current state of a linguistic system shaping and constraining future states.


State of neonatal health care in eight countries of the SAARC region, South Asia: how can we make a difference?
The South Asian Association for Regional Cooperation (SAARC) is an organization of eight countries--Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, Sri Lanka and Afghanistan. The major objectives of this review are to examine trends and progress in newborn and neonatal health care in the region. A landscape analysis of the current state of neonatal mortality, stillbirths and trends over the years for each country and the effective interventions to reduce neonatal mortality and stillbirths was undertaken. A modelling exercise using the Lives Saved Tool (LiST) was also undertaken to determine the impact of scaling up a set of essential interventions on neonatal mortality and stillbirths. The findings demonstrate that there is an unacceptably high and uneven burden of neonatal mortality and stillbirths in the region which together account for 39% of global neonatal deaths and 41% of global stillbirths. Progress is uneven across countries in the region, with five of the eight SAARC countries having reduced their neonatal mortality rate by more than 50% since 1990, while India (43%), Afghanistan (29%) and Pakistan (25%) have made slower progress and will not reach their MDG4 targets. The major causes of neonatal mortality are intrapartum-related deaths, preterm birth complications and sepsis which account for nearly 80% of all deaths. The LiST analysis shows that a gradual increase in coverage of proven available interventions until 2020 followed by a uniform scale-up to 90% of all interventions until 2030 could avert 52% of neonatal deaths (0.71 million), 29% of stillbirths (0.31 million) and achieve a 31% reduction in maternal deaths (0.25 million). The analysis demonstrates that the Maldives and Sri Lanka have done remarkably well while other countries need greater attention and specific focus on strategies to improve neonatal health.


Polarization-resolved near-backscattering of airborne aggregates composed of different primary particles.
We measured the polarization-resolved angular elastic scattering intensity distribution of aggregates composed of primary particles with different shapes and packing densities in the near-backward directions (155°-180°). Specifically, we compare aggregates composed of spherical polystyrene latex spheres, cylinder-like Bacillus subtilis particles, and Arizona road dust, as well as tryptophan particles. We observe clearly differentiable polarization aspect ratios and find that the negative polarization dip is more pronounced in more densely packed aggregates or particles. This work indicates that the polarization aspect ratio in the near-backward direction may be used as a fingerprint to discriminate between aggregates with the same size and overall shape by differences in their constituent particles.


Procedural sedation in the emergency centre.
The performance of safe and effective procedural sedation in the emergency centre has become a core competency in emergency medicine internationally. However, in South Africa clear guidelines are lacking and this guideline attempts to set out the standard for the routine safe use of procedural sedation by clinical staff in emergency centres. The Emergency Medicine Society of South Africa (EMSSA) appointed a task group to analyse the international literature and guidelines, and a draft document was produced which was revised by consensus input from an expert panel. A simple and clear practice guideline has been developed for health professionals working in emergency centres in South Africa. This guideline will help to improve the provision of emergency procedural sedation, which is an important component of the care provided in emergency centres.


Acupuncture for Bell's palsy.
Bell's palsy or idiopathic facial palsy is an acute facial paralysis due to inflammation of the facial nerve. A number of studies published in China have suggested acupuncture is beneficial for facial palsy. The objective of this review was to examine the efficacy of acupuncture in hastening recovery and reducing long-term morbidity from Bell's palsy. We updated the searches of the Cochrane Neuromuscular Disease Group Trials Specialized Register (24 May 2010), The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2010), MEDLINE (January 1966 to May 2010), EMBASE (January 1980 to May 2010), AMED (January 1985 to May 2010), LILACS (from January 1982 to May 2010) and the Chinese Biomedical Retrieval System (January 1978 to May 2010) for randomised controlled trials using 'Bell's palsy' and its synonyms, 'idiopathic facial paralysis' or 'facial palsy' as well as search terms including 'acupuncture'. Chinese journals in which we thought we might find randomised controlled trials relevant to our study were handsearched. We reviewed the bibliographies of the randomised trials and contacted the authors and known experts in the field to identify additional published or unpublished data. We included all randomised controlled trials involving acupuncture by needle insertion in the treatment of Bell's palsy irrespective of any language restrictions. Two review authors identified potential articles from the literature search, extracted data and assessed quality of each trial independently. All disagreements were resolved by discussion between the review authors. The literature search and handsearching identified 49 potentially relevant articles. Of these, six RCTs were included involving 537 participants with Bell's palsy. Two more possible trials were identified in the update than the previous version of this systematic review, but both were excluded because they were not real RCTs. Of the six included trials, five used acupuncture while the other one used acupuncture combined with drugs. No trial reported on the outcomes specified for this review. Harmful side effects were not reported in any of the trials. Poor quality caused by flaws in study design or reporting (including uncertain method of randomisation, allocation concealment and blinding) and clinical differences between trials prevented reliable conclusions about the efficacy of acupuncture. The quality of the included trials was inadequate to allow any conclusion about the efficacy of acupuncture. More research with high quality trials is needed.


The content and conduct of GP consultations for dermatology problems: a cross-sectional study.
Skin complaints are common in primary care, and poor outcomes in long-term conditions are often due to low adherence to treatment. Shared decision making and self-management support may help, yet there is little understanding of patient involvement or the support provided by GPs. To describe the content of primary care consultations for skin problems, including shared decision making practice, delivery of self-management advice, and follow-up. Cross-sectional study of video-recorded UK adult GP consultations and linked data. A coding tool was developed and applied to all consultations with skin problems. Shared decision making was assessed using the observer OPTION5 scale. A total of 45/318 consultations (14.2%) related to one or more skin problems, which were discussed alongside other problems in 71.1% (32/45) of consultations. Of the 100 different problems discussed in these consultations, 51 were dermatological. The mean amount of time spent on skin problems in the consultations was 4 minutes 16 seconds. Medication was recommended for 66.7% (34/51) of skin problems, with low shared decision making (mean OPTION5 score = 10.7). Self-management advice (verbal only) was given for 47.1% (24/51) of skin problems. Most skin problems (84.3%; 43/51) were not referred to secondary care; 32.6% (14/43) of the skin problems not referred were seen again in primary care within 12 weeks, of which 35.7% (5/14) follow-up appointments were not planned. In this study, skin problems were usually presented alongside other complaints and resulted in a medication recommendation. Shared decision making was uncommon and self-management advice not consistently given, with re-attendance for the same problem common. GPs' training should reflect how frequently skin problems are seen and seek to improve patient involvement in decision making and support self-management.


Epidemiological characteristics of orbital cellulitis among adult population in the Split region, Croatia.
There are few diseases in ophthalmology which could have a fatal outcome, one of them is orbital cellulitis. The aim of this article is to give epidemiological analysis of orbital cellulitis in adult patients in the Split region, Croatia. The study was based on a retrospective review of medical records of 53 adult patients with orbital cellulitis treated during the period of 26 years from 1991 to 2016 at the Department of Ophthalmology in the University Hospital of Split. The incidence of orbital cellulitis in adults in the Split region was 0.57. The mean age of the patients was 53.5 ± 19.0 years. Patients were male in 47.2% of the cases and female in 52.8%. The distribution of orbital cellulitis according to seasons shows that it was most common during winter with 20 (37.7%) and in autumn with 16 (30.2%) cases and less frequent in summer with 6 (11.3%) and in spring 11 (20.8%) cases. The most common cause of orbital cellulitis was sinusitis in 33 (62.2%) patients. In total, there were 16 (30.2%) surgical interventions. Orbital cellulitis in adult patients is a relatively rare disease but with a possible fatal ending and damage to vision. It should be diagnosed quickly and treated adequately, very often in cooperation of an ophthalmologist with an otorhinolaryngologist and a maxillofacial surgeon. Orbital cellulitis appears to be more common in colder months, because sinusitis occurred more often then. It is treated with adequate antibiotic application but in almost one third of cases a surgical intervention was necessary.


Clinical and angiographic characteristics of patients likely to have vulnerable plaques: analysis from the PROSPECT study.
This study sought to determine the clinical and angiographic variables that would identify patients with high-risk "vulnerable" coronary plaques. In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, in patients successfully treated for acute coronary syndrome (ACS), plaque composition, plaque burden, and minimal luminal area as detected by 3-vessel radiofrequency intravascular ultrasound (IVUS) imaging were associated with an increased risk of developing future events from untreated atherosclerotic lesions (vulnerable plaques). Whether baseline demographic and angiographic findings can be used to identify patients most likely to have vulnerable coronary plaques has not been examined. On the basis of 3-vessel radiofrequency IVUS imaging, patents in the PROSPECT trial were classified in 2 groups according to whether or not one or more untreated high-risk plaques were present, defined as having ≥2 high-risk features (a thin-cap fibroatheroma, plaque burden ≥70%, and/or minimal luminal area ≤4 mm(2)). The high-risk group (those with one or more high-risk lesions) had higher Framingham risk score (7.5 ± 3.4 vs. 6.9 ± 3.3; p = 0.04), more extensive coronary artery disease, and more nonculprit lesion-related cardiovascular events during the 3-year follow-up (hazard ratio: 2.63; 95% confidence interval: 1.62 to 3.66; p < 0.0001). However, demographic factors had poor discrimination in detecting high-risk patients (area under the curve 0.55), and discrimination was only slightly improved when angiographic variables were entered into the model (area under the curve 0.64). Clinical and angiographic characteristics had poor predictive accuracy in identifying patients with untreated high-risk plaques related to future adverse events. This finding highlights the potential value of comprehensive 3-vessel imaging assessment (either invasive or noninvasive) to evaluate plaque phenotype for more accurate risk stratification of patients admitted with ACS.


Viroid-induced phosphorylation of a host protein related to a dsRNA-dependent protein kinase.
Viroids are very small, unencapsidated RNAs that replicate and induce severe disease in plants without encoding for any proteins. The mechanisms by which the viroid RNA regulates these events and interacts with host factors are unknown. An Mr 68,000 host-encoded protein has been identified that is differentially phosphorylated in extracts from viroid-infected and mock-inoculated tissues. This phosphoprotein is immunologically related to a double-stranded (ds) RNA-dependent protein kinase from virus-infected, interferon-treated human cells. Further, nucleotide photoaffinity labeling indicates that the protein has an ATP binding site. This protein is similar to dsRNA-dependent protein kinases implicated in mammalian systems in the regulation of protein synthesis and virus replication.


Interdisciplinary promises versus practices in medicine: the decoupled experiences of social sciences and humanities scholars.
This paper explores social scientists' and humanities (SSH) scholars' integration within the academic medical research environment. Three questions guided our investigation: Do SSH scholars adapt to the medical research environment? How do they navigate their career within a culture that may be inconsistent with their own? What strategies do they use to gain legitimacy? The study builds on three concepts: decoupling, doxa, and epistemic habitus. Twenty-nine semi-structured interviews were conducted with SSH scholars working in 11 faculties of medicine across Canada. Participants were selected through purposeful and snowball sampling. The data were analyzed by thematic content analysis. For most of our participants, moving into medicine has been a challenging experience, as their research practices and views of academic excellence collided with those of medicine. In order to achieve some level of legitimacy more than half of our participants altered their research practices. This resulted in a dissonance between their internalized appreciation of academic excellence and their new, altered, research practices. Only six participants experienced no form of challenge or dissonance after moving into medicine, while three decided to break with their social science and humanities past and make the medical research community their new home. We conclude that the work environment for SSH scholars in faculties of medicine does not deliver on the promise of inclusiveness made by calls for interdisciplinarity in Canadian health research.


Hip fusion in young adults. Using a medial displacement osteotomy and cobra plate.
Eight consecutive patients, mean age 17.25 years, underwent a medial displacement osteotomy and hip arthrodesis with a nine-hole Cobra plate. A transverse innominate osteotomy facilitated medial displacement of the femoral head and acetabulum. Alignment of the lower limb at 25 degrees flexion, neutral abduction, and neutral rotation was assisted by a long-limbed protractor and Steinmann pins placed in both anterior superior iliac spines. The greater trochanter was reattached to the Cobra plate so that hip abductor function could be restored should the fusion ever be converted to an arthroplasty. No postoperative immobilization was required. All patients had radiographic evidence of union by 12 months. One patient had a postoperative brachial plexus neuropraxia that resolved at three months. One patient required an ipsilateral femoral lengthening for limb-length inequality secondary to collapse of his femoral head before hip fusion. At a mean follow-up interval of 2.8 years (range, one to 4.5 years), all patients had significant improvements in pain (p < 0.05), function (p < 0.01), and gait (p < 0.01). The average preoperative Harris Hip Score of 45 points +/- 8 points (mean +/- SEM) improved to 84 points +/- 2 points (p < 0.01).


Investigation of failure behavior of a thermoplastic elastomer gel.
Gels are increasingly being used in many applications, and it is important to understand how these gels fail subjected to mechanical deformation. Here, we investigate the failure behavior of a thermoplastic elastomer gel (TPEG) consisting of poly(styrene)-poly(isoprene)-poly(styrene) in mineral oil, in tensile mode, under constant stress, and in fracture tests, where the fracture initiates from a predefined crack. In these gels, the poly(styrene) endblocks associate to form spherical aggregates, as captured using SAXS. Shear-rheology experiments indicate that the poly(isoprene) midblocks connecting these aggregates are loosely entangled. The relaxation behavior of these gels has been captured by time-temperature superposition of frequency sweep data and stress-relaxation experiments. The relaxation process in these gels involves endblock pullout from the aggregates and subsequent relaxation of the chains. An unfavorable enthalpic interaction between the endblock and mineral oil results in a significantly large relaxation time. These gels display rate dependent mechanical properties, likely due to the midblock entanglements. Fracture and creep failure tests provide insights into the gel failure mechanism. Creep experiments indicate that these gels fail by a thermally activated process. Fracture experiments capture the energy release rate as a function of crack-tip velocity. The critical energy release rate is estimated by incorporating the friction force the polystyrene chains are subjected to, as those are pulled out of aggregates, and the enthalpic cost to overcome unfavorable interaction between poly(styrene) and mineral oil. Our results provide further insights to the failure behavior of the self-assembled TPEGs.


Pinto Beans (Phaseolus vulgaris L.) Lower Non-HDL Cholesterol in Hamsters Fed a Diet Rich in Saturated Fat and Act on Genes Involved in Cholesterol Homeostasis.
Pinto beans contain multiple active agents such as polyphenols, flavonoids, and saponins, and have been shown to lower cholesterol, but the mechanisms involved in this effect have not been explored. This study was to investigate the changes in cholesterol metabolism in response to whole pinto beans (wPB) and their hulls (hPB) supplemented into a diet rich in saturated fat and the molecular mechanisms potentially responsible for these effects in hamsters. Forty-four 9-wk-old male Golden Syrian hamsters were randomly assigned to 4 diet groups (n = 11), including a 5% (wt:wt) fat diet [normal-fat diet (NF)], a 15% (wt:wt) fat diet [diet rich in saturated fat (HSF), saturated fatty acids accounted for 70% of total fatty acids], or HSF supplemented with 5% (wt:wt) wPB or 0.5% (wt:wt) hPB for 4 wk. Plasma, liver, intestinal, and fecal samples were collected to evaluate multiple cholesterol markers and gene targets. The plasma non-high-density lipoprotein (non-HDL) concentration was significantly reduced in the wPB- and hPB-supplemented groups by 31.9 ± 3.5% and 53.6 ± 3.2%, respectively, compared with the HSF group (P < 0.01), to concentrations comparable with the NF group. The wPB-supplemented hamsters had significantly lower liver cholesterol (45.1%, P < 0.001) and higher fecal cholesterol concentrations (94.8%, P = 0.001) than those fed the HSF. The expressions of hepatic 3-hydroxy-3-methylglutaryl CoA reductase (Hmgcr) and small intestinal acyl-coenzyme A: cholesterol acyltransferase 2 (Acat2) were significantly decreased in animals administered wPB (by 89.1% and 63.8%, respectively) and hPB (by 72.9% and 47.7%, respectively) compared with their HSF-fed counterparts (P < 0.05). The wPB normalized the expression of Acat2 to the level of the NF group. Pinto beans remediated high cholesterol induced by HSF in male hamsters by decreasing hepatic cholesterol synthesis and intestinal cholesterol absorption, effects which were partially exerted by the hulls.


In vivo inhibition of RIPK2 kinase alleviates inflammatory disease.
The RIPK2 kinase transduces signaling downstream of the intracellular peptidoglycan sensors NOD1 and NOD2 to promote a productive inflammatory response. However, excessive NOD2 signaling has been associated with numerous diseases, including inflammatory bowel disease (IBD), sarcoidosis and inflammatory arthritis, making pharmacologic inhibition of RIPK2 an appealing strategy. In this work, we report the generation, identification, and evaluation of novel RIPK2 specific inhibitors. These compounds potently inhibit the RIPK2 tyrosine kinase activity in in vitro biochemical assays and cellular assays, as well as effectively reduce RIPK2-mediated effects in an in vivo peritonitis model. In conjunction with the development of these inhibitors, we have also defined a panel of genes whose expression is regulated by RIPK2 kinase activity. Such RIPK2 activation markers may serve as a useful tool for predicting settings likely to benefit from RIPK2 inhibition. Using these markers and the FDA-approved RIPK2 inhibitor Gefitinib, we show that pharmacologic RIPK2 inhibition drastically improves disease in a spontaneous model of Crohn Disease-like ileitis. Furthermore, using novel RIPK2-specific inhibitors, we show that cellular recruitment is inhibited in an in vivo peritonitis model. Altogether, the data presented in this work provides a strong rationale for further development and optimization of RIPK2-targeted pharmaceuticals and diagnostics.


Are three contact efforts really reflective of a repeated high-intensity effort bout?
The use of 3 or more efforts (running and contact), separated by short recovery periods, is widely used to define a "repeated high-intensity effort" (RHIE) bout in rugby league. It has been suggested that due to fatigue, players become less effective after RHIE bouts; however, there is little evidence to support this. This study determined whether physical performance is reduced after performing 1, 2, or 3 efforts with minimal recovery. Twelve semiprofessional rugby league players (age: 24.5 ± 2.9 years) competed in 3 "off-side" small-sided games (2 × 10-minute halves) with a contact bout performed every 2 minutes. The rules of each game were identical except for the number of contact efforts performed in each bout. Players performed 1, 2, or 3 × 5-second wrestling bouts in the single-, double- and triple-contact game, respectively. Movement demands of each game were monitored using global positioning system units. From the first to the second half, there were trivial reductions in relative distance during the single-contact game (ES = -0.13 ± 0.12), small reductions during the double-contact game (ES = -0.47 ± 0.24), and moderate reductions during the triple-contact game (ES = -0.74 ± 0.27). These data show that running intensity is progressively reduced as the number of contact efforts per bout is increased. Targeting defensive players and forcing them to perform 2 or more consecutive contact efforts is likely to lead to greater reductions in running intensity. Conditioning performing multiple contact efforts while maintaining running intensity should therefore be incorporated into training for contact team sports.


The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: A common epileptic encephalopathy.
Pyridoxine dependent epilepsy (PDE) is a treatable epileptic encephalopathy characterized by a positive response to pharmacologic doses of pyridoxine. Despite seizure control, at least 75% of individuals have intellectual disability and developmental delay. Current treatment paradigms have resulted in improved cognitive outcomes emphasizing the importance of an early diagnosis. As genetic testing is increasingly accepted as first tier testing for epileptic encephalopathies, we aimed to provide a comprehensive overview of ALDH7A1 mutations that cause PDE. The genotypes, ethnic origin and reported gender was collected from 185 subjects with a diagnosis of PDE. The population frequency for the variants in this report and the existing literature were reviewed in the Genome Aggregation Database (gnomAD). Novel variants identified in population databases were also evaluated through in silico prediction software and select variants were over-expressed in an E.coli-based expression system to measure α-aminoadipic semialdehyde dehydrogenase activity and production of α-aminoadipic acid. This study adds 47 novel variants to the literature resulting in a total of 165 reported pathogenic variants. Based on this report, in silico predictions, and general population data, we estimate an incidence of approximately 1:64,352 live births. This report provides a comprehensive overview of known ALDH7A1 mutations that cause PDE, and suggests that PDE may be more common than initially estimated. Due to the relative high frequency of the disease, the likelihood of under-diagnosis given the wide clinical spectrum and limited awareness among clinicians as well as the cognitive improvement noted with early treatment, newborn screening for PDE may be warranted.


Dietary intake in pregnancy. A comparison between 49 Cambridgeshire women and current recommended intake.
The mean daily nutrient intakes from dietary sources of 49 pregnant women in the third trimester of normal pregnancy were assessed using a 7-day weighed inventory method and standard food tables. Mean daily intakes of all major nutrients reached DHSS recommended levels, with the exceptions of energy (2065 kcal/8.65 MJ), proportion of energy derived from carbohydrate (48 per cent), calcium (1047 mg), and vitamin D (2.58 micrograms). These results are in agreement with those of comparable published studies and lend support to suggestions that some of the increased requirements in pregnancy may be being met by physiological adaptation, without the need for greatly increased dietary intakes, or for indiscriminate vitamin and mineral supplementation. For seven women with low weight gain (less than 8 kg at 36 weeks; mean 6.97 kg), mean daily intakes of most nutrients were lower, and were below recommended levels for energy (1770 kcal/7.4 MJ), ascorbic acid (47.4 mg), vitamin D (2.18 micrograms), calcium (980 mg), and iron (10.5 mg). Proportional intakes of carbohydrate (50 per cent) and dietary fibre (20.1 g/day) however, tended to be higher in this group.


Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy.
Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease characterized by contractures and proximal weakness, which can be caused by mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However, there may be additional causal genes to identify as in ∼50% of BM cases no mutations in the COL6 genes are identified. In a cohort of -24 patients with a BM-like phenotype, we first sequenced 12 candidate genes based on their function, including genes for known binding partners of collagen VI, and those enzymes involved in its correct post-translational modification, assembly and secretion. Proceeding to whole-exome sequencing (WES), we identified mutations in the COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with interrupted triple helices) in five individuals from two families. Both families showed dominant inheritance with a clinical phenotype resembling classical BM. Family 1 had a single-base substitution that led to the replacement of one glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating pattern, and Family 2 had a missense mutation, which created a mutant protein with an unpaired cysteine residue. Abnormality at the protein level was confirmed in both families by the intracellular retention of collagen XII in patient dermal fibroblasts. The mutation in Family 2 leads to the up-regulation of genes associated with the unfolded protein response (UPR) pathway and swollen, dysmorphic rough-ER. We conclude that the spectrum of causative genes in extracellular matrix (ECM)-related myopathies be extended to include COL12A1.


Risk associated with a systematic search of extended-spectrum β-lactamase-producing Enterobacteriaceae.
We evaluated 74 children with previous fecal extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae colonization who were hospitalized and receiving a course of antibiotic therapy for suspected infection. Sixty-four patients (86.5%) received a carbapenem agent. Only 3 patients were infected with an ESBL-producing Enterobacteriaceae. Sixty-one (95%) initial antibiotic courses were considered excessive and required deescalation; however, deescalation was accomplished in only 38 patients (62%). This suggests the need for an ESBL control program to decrease carbapenem use and thereby limit carbapenem resistance in gram-negative bacilli.


Acceptability and feasibility of a Japanese version of STrAtegies for RelaTives (START-J): A manualized coping strategy program for family caregivers of relatives living with dementia.
The rising older population in Japan is associated with a rise in cases of dementia. Support for the increased number of family caregivers of people living with dementia is crucial, as caring may negatively affect a family caregiver's health. This study seeks to evaluate the feasibility and applicability of a recently developed Japanese version of START (STrAtegies for RelaTives). START is a psychosocial coping intervention program developed in the United Kingdom that has been shown to improve caregivers' mood and quality of life in a randomized controlled trial. We made changes to START (e.g., idioms, linguistic nuance, and providing care insurance information suited for Japan) to make it culturally appropriate. Fourteen Japanese female family caregivers of relatives with mild dementia (n = 10) or mild cognitive impairment (n = 4) were referred to the study, but six were excluded owing to illness and busyness. This single-arm study had a before-after trial evaluating psychological outcomes including depression, anxiety, quality of life, and subjective care burden. The acceptance retention and satisfaction rate suggest the feasibility and acceptability of the START program; 8/14 (>55%) eligible, prospective participants consented and were included in this study, all (8/8) of whom completed all START sessions. The mean program satisfaction score was 30.25 (standard deviation = 2.25) out of a potential 32. The results suggest that it is feasible and acceptable to deliver START in Japanese and based on the results of analysis using a linear mixed model, there is initial indication that the intervention improved family caregivers' quality of life, depressive symptoms, and care burden.


Weight loss leads to reductions in inflammatory biomarkers after a very-low-carbohydrate diet and a low-fat diet in overweight men.
In recent years, it has become apparent that low-grade vascular inflammation plays a key role in all stages of the pathogenesis of atherosclerosis. Weight loss has been shown to improve blood inflammatory markers; however, it is unknown if weight-loss diets varying in macronutrient composition differentially affect inflammatory responses. The primary purpose of the present study was to compare a very-low-carbohydrate diet and a low-fat weight-loss diet on inflammatory biomarkers in overweight men. In a randomized cross-over design, 15 overweight men (body fat, >25%; body mass index, 34 kg/m2) consumed two experimental weight-loss diets for two consecutive 6-week periods: a very-low-carbohydrate diet (<10% energy via carbohydrate) and a low-fat diet (<30% energy via fat). Both the low-fat and the very-low-carbohydrate diets resulted in significant decreases in absolute concentrations of hsTNF-alpha (high-sensitivity tumour necrosis factor-alpha), hsIL-6 (high-sensitivity interleukin-6), hsCRP (high-sensitivity C-reactive protein) and sICAM-1 (soluble intercellular cell-adhesion molecule-1). There was no significant change in absolute sP-selectin (soluble P-selectin) concentrations after either diet. Normalized inflammatory values represented as the delta change per 1 kg reduction in body mass showed a significant difference between the two diets only for sP-selectin (P<0.05). In summary, energy-restricted low-fat and very-low-carbohydrate diets both significantly decreased several biomarkers of inflammation. These data suggest that, in the short-term, weight loss is primarily the driving force underlying the reductions in most of the inflammatory biomarkers.


A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities.
Posttraumatic stress disorder (PTSD) is a serious and debilitating condition with a prevalence rate of approximately 8% in the United States. Given the number of veterans returning from conflicts around the globe with PTSD, and the substantial number of civilians experiencing traumas, new perspectives on the biology of PTSD are needed. Based on the concept that PTSD is a disorder of stress response systems, numerous studies have suggested changes in hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system function in patients with PTSD. Given that both glucocorticoids and catecholamines exert powerful effects on the immune system, it is surprising that relatively few studies have examined immune changes in patients with PTSD. Moreover, patients with PTSD are known to have increased rates of comorbidity with somatic disorders that involve immune and inflammatory processes. Patients with PTSD have been found to exhibit a number of immune changes including increased circulating inflammatory markers, increased reactivity to antigen skin tests, lower natural killer cell activity, and lower total T lymphocyte counts. Studies with humans and rodents suggest that certain proinflammatory cytokines are able to induce neurochemical and behavioral changes that resemble some key features of PTSD. This short article reviews immune alterations in PTSD, and considers possible mechanisms by which such changes may be related to neuroendocrine alterations and medical comorbidities of PTSD.


A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis.
Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA. The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls. The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-γ, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-γ and IL-13 to CMV/EBV stimulation were associated with greater joint damage. A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA.


High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse.
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.


Rose-K versus Soper contact lens in keratoconus: a randomized comparative trial.
To perform a comparative evaluation of the efficacy and acceptability of Rose-K and Soper contact lenses in Keratoconus. Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi. A randomized comparative clinical trial was performed in keratoconic eyes fitted with Rose-K (Rose-K group) and Soper (Soper group) contact lenses. Patients data were evaluated for best spectacle corrected visual acuity, best contact lens corrected visual acuity (BCLCVA), corneal topography, glare acuity, contrast sensitivity, tear function tests and specular microscopy. Patients were also asked to complete a self-reported comfort questionnaire at each visit. Sixty eyes were randomized to the Rose-K and Soper groups. The two groups were comparable in all the baseline parameters. There was a statistically significant improvement in BCLCVA in both groups at 3 months (P < 0.01, both groups). The difference between in BCLCVA in both groups was not statistically significant. In both groups, there was a significant improvement in the comfort score at 3 months compared to baseline (P < 0.05, both group). The Rose-K group had statistically significantly better scores at 1 and 3 months compared with the Soper group (P = 0.006 and P < 0.001 respectively). Both groups were associated with a significant (P < 0.01), but comparable improvement in glare acuity at 3 months. There was a significant improvement in contrast sensitivity at 3 months in both groups (P < 0.01); the Rose-K group was significantly better than the Soper group at 1 and 3 months (P = 0.001 and 0.002 respectively). The mean number of trial lenses required for fitting Rose-K lens (2.00 ± 0.59) was significantly lower than the Soper lens (3.43 ± 0.82; P < 0.001). Both the contact lens designs provide an equal improvement in visual acuity in patients with Keratoconus. However, Rose-K contact lens provides greater comfort, better quality of vision and requires less chair time compared with the Soper lens and hence may possibly have a greater acceptability.


Handedness and Graspability Modify Shifts of Visuospatial Attention to Near-Hand Objects.
We examined how factors related to the internal representation of the hands (handedness and grasping affordances) influence the distribution of visuospatial attention near the body. Left and right handed participants completed a covert visual cueing task, discriminating between two target shapes. In Experiment 1, participants responded with either their dominant or non-dominant hand. In Experiment 2, the non-responding hand was positioned below one of two target placeholders, aligned with the shoulder. In Experiment 3 the near-monitor hand was positioned under the placeholder in the opposite region of hemispace, crossed over the body midline. For Experiments 2 & 3, in blocked trials the palmar and back-of hand surfaces were directed towards the target placeholder such that targets appeared towards either the graspable or non-graspable space of the hand respectively. In Experiment 2, both left and right handers displayed larger accuracy cueing effects for targets near versus distant from the graspable space of the right hand. Right handers also displayed larger response time cueing effects for objects near the graspable versus non-graspable region of their dominant hand but not for their non-dominant hands. These effects were not evident for left-handers. In Experiment 3, for right handers, accuracy biases for near hand targets were still evident when the hand was crossed over the body midline, and reflected hand proximity but not functional orientation biases. These findings suggest that biased visuospatial attention enhances object identity discrimination near hands and that these effects are particularly enhanced for right-handers.


Viruses and thyroiditis: an update.
Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.


Statistical issues in life course epidemiology.
There is growing recognition that the risk of many diseases in later life, such as type 2 diabetes or breast cancer, is affected by adult as well as early-life variables, including those operating prior to conception and during the prenatal period. Most of these risk factors are correlated because of common biologic and/or social pathways, while some are intrinsically ordered over time. The study of how they jointly influence later ("distal") disease outcomes is referred to as life course epidemiology. This area of research raises several issues relevant to the current debate on causal inference in epidemiology. The authors give a brief overview of the main analytical and practical problems and consider a range of modeling approaches, their differences determined by the degree with which associations present (or presumed) among the correlated explanatory variables are explicitly acknowledged. Standard multiple regression (i.e., conditional) models are compared with joint models where more than one outcome is specified. Issues arising from measurement error and missing data are addressed. Examples from two cohorts in the United Kingdom are used to illustrate alternative modeling strategies. The authors conclude that more than one analytical approach should be adopted to gain more insight into the underlying mechanisms.


A preclinical model of TB meningitis to determine drug penetration and activity at the sites of disease.
Tuberculosis meningitis (TBM) is essentially treated with the first-line regimen used against pulmonary tuberculosis, with a prolonged continuation phase. However, clinical outcomes are poor in comparison, for reasons that are only partially understood, highlighting the need for improved preclinical tools to measure drug distribution and activity at the site of disease. A predictive animal model of TBM would also be of great value to prioritize promising drug regimens to be tested in clinical trials, given the healthy state of the development pipeline for the first time in decades. Here, we report the optimization of a rabbit model of TBM disease induced via inoculation of Mycobacterium tuberculosis into the cisterna magna, recapitulating features typical of clinical TBM: neurological deterioration within months post-infection, acid-fast bacilli in necrotic lesions in the brain and spinal cord, and elevated lactate levels in cerebrospinal fluid (CSF). None of the infected rabbits recovered or controlled the disease. We used young adult rabbits, the size of which allows for spatial drug quantitation in critical compartments of the central nervous system that cannot be collected in clinical studies. To illustrate the translational value of the model, we report the penetration of linezolid from plasma into the CSF, meninges, anatomically distinct brain areas, cervical spine, and lumbar spine. Across animals, we measured the bacterial burden concomitant with neurological deterioration, offering a useful readout for drug efficacy studies. The model thus forms the basis for building a preclinical platform to identify improved regimens and inform clinical trial design.


Fabrication of Biohybrid Cellulose Acetate-Collagen Bilayer Matrices as Nanofibrous Spongy Dressing Material for Wound-Healing Application.
Tissue engineering is currently one the fastest growing engineering fields, requiring fabrication of advanced and multifunctional materials to be used as scaffolds or dressing for tissue regeneration. In this work, a bilayer matrix was fabricated by electrospinning of a hybrid cellulose acetate nanofibers (CA) containing bioactive latex or Ciprofloxacin over highly interconnected collagen (CSPG) 3D matrix previously obtained by a freeze-drying process. The bilayer matrix was fabricated with a nanofibrous part as the primary (top) layer and a spongy porous part as the secondary (bottom) layer by combining electrospinning and freeze-drying techniques to enhance the synergistic effect of both materials corresponding to physical and biological properties. The final material was physicochemically characterized using Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The bilayer matrix exhibited nanofibrous and 3D porous structure with properties such as high porosity, swelling, and stability required for soft-tissue-engineering applications. Furthermore, the in vitro biological and fluorescence properties of the matrix were tested against NIH 3T3 fibroblast and human keratinocyte (HaCaT) cell lines and showed good cell adhesion and proliferation over the bilayer matrix. Thus, the synergistic combination of nanofibrous material deposition onto to the collagenous porous material has proved efficient in the fabrication of a bilayer matrix for skin-tissue-engineering applications.


The local structure of self-doped BiS2-based layered systems as a function of temperature.
We have studied the local structure of layered Eu(La,Ce)FBiS2 compounds by Bi L3-edge extended X-ray absorption fine structure (EXAFS) measurements as a function of temperature. We find that the BiS2 sub-lattice is largely distorted in EuFBiS2, characterized by two different in-plane Bi-S1 distances. The distortion is marginally affected by partial substitutions of Ce (Eu0.5Ce0.5FBiS2) and La (Eu0.5La0.5FBiS2). The temperature dependence of the local structure distortion reveals an indication of possible charge density wave like instability in the pristine self-doped EuFBiS2 and Ce substituted Eu0.5Ce0.5FBiS2 while it is suppressed in La substituted Eu0.5La0.5FBiS2. In compounds with higher superconducting transition temperature, the axial Bi-S2 bond distance is elongated and the related bond stiffness decreased, suggesting some important role of this in the charge transfer mechanism for self-doping in the active BiS2-layer. In-plane Bi-S1 distances are generally softer than the axial Bi-S2 distance and they suffer further softening by the substitutions. The results are discussed in relation to an important role of the Bi defect chemistry driven asymmetric local environment in the physical properties of these materials.


Biological motion coding in the brain: analysis of visually driven EEG functional networks.
Herein, we address the time evolution of brain functional networks computed from electroencephalographic activity driven by visual stimuli. We describe how these functional network signatures change in fast scale when confronted with point-light display stimuli depicting biological motion (BM) as opposed to scrambled motion (SM). Whereas global network measures (average path length, average clustering coefficient, and average betweenness) computed as a function of time did not discriminate between BM and SM, local node properties did. Comparing the network local measures of the BM condition with those of the SM condition, we found higher degree and betweenness values in the left frontal (F7) electrode, as well as a higher clustering coefficient in the right occipital (O2) electrode, for the SM condition. Conversely, for the BM condition, we found higher degree values in central parietal (Pz) electrode and a higher clustering coefficient in the left parietal (P3) electrode. These results are discussed in the context of the brain networks involved in encoding BM versus SM.


Influence of sodium hypochlorite/etidronic acid combination and SmearOFF on push-out bond strength of fiber posts to root dentin.
The aim was to evaluate the effects of different irrigation protocols on the bonding ability of fiber posts on root canal dentin through push-out test and the dentin tubule penetration of luting cement by confocal laser scanning microscope (CLSM). Forty-eight single-rooted premolars were divided into six groups (n=8) based on post space irrigation protocols: Saline 0.85%; Etidronate 18% (HEBP); EDTA 17%; NaOCl 5.25%+EDTA 17%; NaOCl 2.5%/HEBP 9% combination; SmearOFF. Two specimens per group were assessed with CLSM. The push-out test and the failure analysis were performed. Whilst EDTA had the highest bond strength at the coronal and middle thirds, it was not statistically significant compared to saline, HEBP, and NaOCl/HEBP at the middle third (p>0.05). Cement/dentin adhesive failures were predominant (41.9%) and the intratubular fluorescence intensity was significant among the groups (p<0.05). EDTA resulted in highest bond strength values and dentinal penetration.


Genome-wide identification of in vivo protein-DNA binding sites from ChIP-Seq data.
ChIP-Seq, which combines chromatin immunoprecipitation (ChIP) with ultra high-throughput massively parallel sequencing, is increasingly being used for mapping protein-DNA interactions in-vivo on a genome scale. Typically, short sequence reads from ChIP-Seq are mapped to a reference genome for further analysis. Although genomic regions enriched with mapped reads could be inferred as approximate binding regions, short read lengths (approximately 25-50 nt) pose challenges for determining the exact binding sites within these regions. Here, we present SISSRs (Site Identification from Short Sequence Reads), a novel algorithm for precise identification of binding sites from short reads generated from ChIP-Seq experiments. The sensitivity and specificity of SISSRs are demonstrated by applying it on ChIP-Seq data for three widely studied and well-characterized human transcription factors: CTCF (CCCTC-binding factor), NRSF (neuron-restrictive silencer factor) and STAT1 (signal transducer and activator of transcription protein 1). We identified 26 814, 5813 and 73 956 binding sites for CTCF, NRSF and STAT1 proteins, respectively, which is 32, 299 and 78% more than that inferred previously for the respective proteins. Motif analysis revealed that an overwhelming majority of the identified binding sites contained the previously established consensus binding sequence for the respective proteins, thus attesting for SISSRs' accuracy. SISSRs' sensitivity and precision facilitated further analyses of ChIP-Seq data revealing interesting insights, which we believe will serve as guidance for designing ChIP-Seq experiments to map in vivo protein-DNA interactions. We also show that tag densities at the binding sites are a good indicator of protein-DNA binding affinity, which could be used to distinguish and characterize strong and weak binding sites. Using tag density as an indicator of DNA-binding affinity, we have identified core residues within the NRSF and CTCF binding sites that are critical for a stronger DNA binding.


[Opioid Induced Pituitary Dysfunction].
A 77-year-old woman with a history of anal squamous cell carcinoma was admitted because of malaise, diarrhea and nausea, in addition to back pain related to a verte- bral compression fracture. During the course of treatment, opioid therapy was initiated, following which the patient became progressively hypotensive and hyponatraemic and respiratory drive progressively decreased. Serum levels of cortisol, TSH and LH were decreased and prolactin slightly elevated, but a Synacthen test and brain MRI turned out normal, suggesting a diagnosis of opioid-induced pituitary dysfunction. The patient was given glucocorticoid replacement therapy with good results. Here we present a case of this serious but less well recognised side-effect of opioids.


Vibroacoustic sound therapy improves pain management and more.
Vibroacoustic therapy is a new sound technology that uses audible sound vibrations to reduce symptoms, invoke relaxation, and alleviate stress. This technology is developed based on the recognition that external vibration can influence body function. Research demonstrates the effectiveness of vibroacoustic therapy. Implications for nurses include investigating the possibilities of vibroacoustic therapy in various nursing settings to promote patient well-being and improve the therapeutic environment.