One-year, efficacy and safety open label study, with a single injection of a new hyaluronan for knee OA: the SOYA trial

[Abstract] Purpose. To assess the efficacy and safety of a single injection of a new formulation of hyaluronic acid (MPS-HA2%) in patients with symptomatic knee osteoarthritis after 12 months’ follow-up. Patients and Methods. Prospective, single-arm, multicentre, open-label, 12-month follow-up study. Patients with Kellgren–Lawrence (KL) 2–3 and visual analogue scale (VAS) pain scores of ≥40–< 80 mm received a single injection of MPS-HA2%. The primary outcome was the reduction in VAS pain scores from baseline, and the secondary outcomes were the Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index, the minimum clinically important improvement (MCII), and patient and investigator global assessments (PGA, IGA) measured on 5-point Likert scale. Adverse events were recorded throughout the study for safety purposes. Results. A total of 101 patients (mean age: 68 years; 74% female; and 78% overweight) were included. The mean reduction in pain at 12 months was 37.7%; the total WOMAC score improved by 36.5% and the pain, stiffness and physical function subscores returned improvements of 32.1%, 34.1% and 32.7%, respectively (p=0.0001 with respect to baseline). At 12 months, a statistically significant 62.2% of patients obtained an improvement equal to or greater than the MCII. The mean PGA score at baseline was 2.44 and 1.46 at 12 months (p<0.05), and the mean IGA scores at equivalent timepoints were 2.29 and 1.48 (p<0.05). Fourteen patients received a second injection at the 6-month follow-up visit. Eight patients reported a total of 12 treatment-related adverse events that were local, non-serious and of mild-to-moderate intensity. Conclusion. With just a single intra-articular injection, this not controlled trial suggests that MPS-HA2% is effective 12 months after the procedure in most cases. Patient tolerability and safety were both optimal (NCT03852914)

Ammonite stratigraphy of a Toarcian (Lower Jurassic) section on Nagy-Pisznice Hill (Gerecse Mts, Hungary)

Abstract In the Jurassic rocks exposed in a small abandoned quarry on the northwestern edge of Nagy-Pisznice Hill in the Gerecse Mts, fairly well preserved parts of a crocodile skeleton was found in 1996. The bed which yielded the skeletal remains is the uppermost layer of the Kisgerecse Marl Formation exposed here and was determined as belonging to the Upper Toarcian Grammoceras thouarsense Zone. The beds of the sequence above and below were carefully sampled in the late 1990s, and the encountered ammonites were evaluated biostratigraphically. As a result, the Lower Toarcian Harpoceras serpentinum Zone, the Middle Toarcian Hildoceras bifrons and Merlaites gradatus Zones, and the Upper Toarcian Grammoceras thouarsense and Geczyceras speciosum Zones were identified. Within most of these zones the subzones and even the faunal horizons were successfully recognized. The lowermost beds above the underlying Pliensbachian red limestone did not yield any fossils; thus the lowermost Toarcian Dactylioceras tenuicostatum Zone could not be documented. The highest Toarcian ammonite zones also remained unidentified, because the beds of the Tölgyhát Limestone above were not sampled all the way up. This paper presents the lithostratigraphic and biostratigraphic details of the sequence, and the paleontological descriptions of the most important ammonites

Pep1, a Secreted Effector Protein of Ustilago maydis, Is Required for Successful Invasion of Plant Cells

The basidiomycete Ustilago maydis causes smut disease in maize. Colonization of the host plant is initiated by direct penetration of cuticle and cell wall of maize epidermis cells. The invading hyphae are surrounded by the plant plasma membrane and proliferate within the plant tissue. We identified a novel secreted protein, termed Pep1, that is essential for penetration. Disruption mutants of pep1 are not affected in saprophytic growth and develop normal infection structures. However, Δpep1 mutants arrest during penetration of the epidermal cell and elicit a strong plant defense response. Using Affymetrix maize arrays, we identified 116 plant genes which are differentially regulated in Δpep1 compared to wild type infections. Most of these genes are related to plant defense. By in vivo immunolocalization, live-cell imaging and plasmolysis approaches, we detected Pep1 in the apoplastic space as well as its accumulation at sites of cell-to-cell passages. Site-directed mutagenesis identified two of the four cysteine residues in Pep1 as essential for function, suggesting that the formation of disulfide bridges is crucial for proper protein folding. The barley covered smut fungus Ustilago hordei contains an ortholog of pep1 which is needed for penetration of barley and which is able to complement the U. maydis Δpep1 mutant. Based on these results, we conclude that Pep1 has a conserved function essential for establishing compatibility that is not restricted to the U. maydis / maize interaction

A Novel Pathogenicity Gene Is Required in the Rice Blast Fungus to Suppress the Basal Defenses of the Host

For successful colonization and further reproduction in host plants, pathogens need to overcome the innate defenses of the plant. We demonstrate that a novel pathogenicity gene, DES1, in Magnaporthe oryzae regulates counter-defenses against host basal resistance. The DES1 gene was identified by screening for pathogenicity-defective mutants in a T-DNA insertional mutant library. Bioinformatic analysis revealed that this gene encodes a serine-rich protein that has unknown biochemical properties, and its homologs are strictly conserved in filamentous Ascomycetes. Targeted gene deletion of DES1 had no apparent effect on developmental morphogenesis, including vegetative growth, conidial germination, appressorium formation, and appressorium-mediated penetration. Conidial size of the mutant became smaller than that of the wild type, but the mutant displayed no defects on cell wall integrity. The Δdes1 mutant was hypersensitive to exogenous oxidative stress and the activity and transcription level of extracellular enzymes including peroxidases and laccases were severely decreased in the mutant. In addition, ferrous ion leakage was observed in the Δdes1 mutant. In the interaction with a susceptible rice cultivar, rice cells inoculated with the Δdes1 mutant exhibited strong defense responses accompanied by brown granules in primary infected cells, the accumulation of reactive oxygen species (ROS), the generation of autofluorescent materials, and PR gene induction in neighboring tissues. The Δdes1 mutant displayed a significant reduction in infectious hyphal extension, which caused a decrease in pathogenicity. Notably, the suppression of ROS generation by treatment with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, resulted in a significant reduction in the defense responses in plant tissues challenged with the Δdes1 mutant. Furthermore, the Δdes1 mutant recovered its normal infectious growth in DPI-treated plant tissues. These results suggest that DES1 functions as a novel pathogenicity gene that regulates the activity of fungal proteins, compromising ROS-mediated plant defense

MoVam7, a Conserved SNARE Involved in Vacuole Assembly, Is Required for Growth, Endocytosis, ROS Accumulation, and Pathogenesis of Magnaporthe oryzae

Soluble NSF attachment protein receptor (SNARE) proteins play a central role in membrane fusion and vesicle transport of eukaryotic organisms including fungi. We previously identified MoSce22 as a homolog of Saccharomyces cerevisiae SNARE protein Sec22 to be involved in growth, stress resistance, and pathogenicity of Magnaporthe oryzae. Here, we provide evidences that MoVam7, an ortholog of S. cerevisiae SNARE protein Vam7, exerts conserved functions in vacuolar morphogenesis and functions in pathogenicity of M. oryzae. Staining with neutral red and FM4-64 revealed the presence of abnormal fragmented vacuoles and an absence of the Spitzenkörper body in the ΔMovam7 mutant. The ΔMovam7 mutant also exhibited reduced vegetative growth, poor conidiation, and failure to produce the infection structure appressorium. Additionally, treatments with cell wall perturbing agents indicated weakened cell walls and altered distributions of the cell wall component chitin. Furthermore, the ΔMovam7 mutant showed a reduced accumulation of reactive oxygen species (ROS) in the hyphal apex and failed to cause diseases on the rice plant. In summary, our studies indicate that MoVam7, like MoSec22, is a component of the SNARE complex whose functions in vacuole assembly also underlies the growth, conidiation, appressorium formation, and pathogenicity of M. oryzae. Further studies of MoVam7, MoSec22, and additional members of the SNARE complex are likely to reveal critical mechanisms in vacuole formation and membrane trafficking that is linked to fungal pathogenicity

Concentration Endurance Test (d2): Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Concentration Endurance Test (d2) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the d2 test as part of a larger neuropsychological battery. The Total number of items processed (TN), Total number of correct responses (CR), Total performance (TP), and Concentration performance (CP) scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, such that scores increased linearly as a function of age. TN scores were affected by age2 for Guatemala and Puerto Rico; CR scores were affected by age2 for Mexico; TP scores were affected by age2 for Chile, Mexico, Puerto Rico, and Spain; and CP scores for Mexico and Spain. Models indicated that children whose parents had a MLPE >12 years obtained higher scores compared to children whose parents had a MLPE≤12 years for Mexico and Spain in all scores, and Puerto Rico for TN, CR, and TP, and Guatemala and Paraguay for CP scores. Sex affect the scores for Ecuador and Honduras (CP scores). CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the d2 test in pediatric populations

Global Sustainability Under Uncertainty: How Do Multinationals Craft Regulatory Policies?

Multinational corporations are increasingly mindful of the significance of sustainability transitions and the need for operations that are energy efficient and environmentally sound. Achieving sustainability under conditions of uncertainty entails the involvement of multiple stakeholders in initiating and carrying outsustainability-focused initiatives. Using longitudinal analysis of Royal Dutch Shell’s sustainability policies, we developed an integrated model to elucidate how uncertainty influences sustainability policies in the specific context of multinational corporations (hereinafter – MNCs). We identified three phases in theevolution of Shell’s sustainability innovation: a self-reflective phase (2000–2003) characterized by intense pressure from climate advocacy groups, an investment phase (2004–2006) for which the MNC attempted to rise to the waste disposal and pollution challenge through renewable sources of energy, and a reorganization phase (2007–2010) to streamline operations. We also uncovered themes that influence how regulatory policies are crafted: responding positively to the “community’s voice”, risk spreading through joint ventures, revenue transparency for government accountability and reporting innovation that confronts hard truths. The practical implications are outlined

Multinationals’ Accountability on Sustainability: The Evolution of Third-party Assurance of Sustainability Reports

In this article we explore how multinational corporations (MNCs) adopt assurance practices to develop and sustain organizational accountability for sustainability. Using a panel of Fortune Global 250 firms over a period of 10 years, we document the diffusion patterns of third-party assurance of sustainability reports. We specifically investigate how evolving auditing practices, namely diversity of assurance standards and type of assurance providers, shape the quality of sustainability assurance statements. The results illustrate great variability in the adoption of assurance practices in the formative stages of this novel market. Our descriptive analysis indicates the relevance of external institutional pressures as well as internal resources and capabilities as underlying factors driving the adoption of assurance. Our evidence also suggests that several MNCs project a decoupled or symbolic image of accountability through assurance, thereby undermining the credibility of these verification practices. The paper contributes to the emerging literature on international accountability standards and emphasizes the need to enhance theory-based, cross-disciplinary knowledge related to auditing and accountability processes for sustainability

First biostratigraphic data of the evaporitic groups in the Fortuna Basin (Betic Cordillera)

The present work offers the first biostratigraphic calibration based on calcareous nannoplankton of the three evaporitic assemblages in the Rio Chicamo section. The A. primus FAD is registered at the upper part of the Sanel marls, above the lower gypsum, and bellow the Tale gypsum. The A. delicatus FAD, and the A. amplificus FAD occurs in the lower and upper part of the Chicamo Cycles, respectively, which allow to calibrate the Chicamo Cycles reversal as the chron C3Ar. The Tortonian/Messinian boundary is found at the Tale gypsum.Published231-2342.2. Laboratorio di paleomagnetismoN/A or not JCRreserve