Potential implantable nanofibrous biomaterials combined with stem cells for subchondral bone regeneration

The treatment of osteochondral defects remains a challenge. Four scaffolds were produced using Food and Drug Administration (FDA)-approved polymers to investigate their therapeutic potential for the regeneration of the osteochondral unit. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) scaffolds were made by electrohydrodynamic techniques. Hydroxyapatite (HAp) and/or sodium hyaluronate (HA) can be then loaded to PCL nanofibers and/or PVP particles. The purpose of adding hydroxyapatite and sodium hyaluronate into PCL/PVP scaffolds is to increase the regenerative ability for subchondral bone and joint cartilage, respectively. Humanbone marrow-derived mesenchymal stem cells (hBM-MSCs) were seeded on these biomaterials. The biocompatibility of these biomaterials in vitro and in vivo, as well as their potential to support MSC differentiation under specific chondrogenic or osteogenic conditions, were evaluated. We show here that hBM-MSCs could proliferate and differentiate both in vitro and in vivo on these biomaterials. In addition, the PCL-HAp could effectively increase the mineralization and induce the differentiation of MSCs into osteoblasts in an osteogenic condition. These results indicate that PCL-HAp biomaterials combined with MSCs could be a beneficial candidate for subchondral bone regeneration

Retrospective, observational study in patients receiving a dexamethasone intravitreal implant 0.7 mg for macular oedema secondary to retinal vein occlusion

PURPOSE To retrospectively evaluate the re-injection interval, efficacy and safety of dexamethasone (DEX) intravitreal implant 0.7 mg in the treatment of macular oedema (ME) due to retinal vein occlusion (RVO) in Germany in 2009-2012. METHODS Retrospective, multicentre, anonymised observational study of data collected from the first DEX implant 0.7 mg injection through 3-6 months following the last injection. Data were included if the patient was \textgreater18 years old, had a diagnosis of ME secondary to branch or central RVO, and received at least 2 DEX implant 0.7 mg injections during routine practice. RESULTS Data from 87 patients were analysed. Mean time to re-injection between first and second treatments was 5.03 months in the total RVO population, and 5.46 and 4.52 months for the branch and central RVO subpopulations, respectively. An intraocular pressure increase of \textgreater25 mm Hg was recorded in 20% of patients, and 34% of patients began treatment with anti-glaucoma medication, but surgery was not needed for this condition. CONCLUSIONS DEX implant 0.7 mg was found to be well tolerated and effective with repeat treatments in clinical practice

EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2015)

The EURL ECVAM status report provides an update on the progress made in the development, validation and regulatory acceptance of alternative methods and approaches and their dissemination since the last report published in June 2014. It is informing on ongoing research and development activities, validation studies, peer reviews, recommendations, strategies and regulatory/international acceptance of alternative methods and approaches and dissemination activities. R&D activities within large European or International consortia continued in toxicity areas where 3Rs solutions are more difficult to find due to the underlying complexity of the area. On the other hand, toxicity areas where promising non-animal approaches have been developed, their validation and regulatory acceptance/international adoption could be progressed. Particular emphasis was given to the best and most intelligent combination and integration of these different non-animal approaches to ultimately obtain the required information without resorting to animal testing.JRC.I.5-Systems Toxicolog

EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2016)

Replacement, Reduction and Refinement of animal testing is anchored in EU legislation. Alternative non-animal approaches facilitate a shift away from animal testing. Cell-based methods and computational technologies are integrated to translate molecular mechanistic understanding of toxicity into safety testing strategies.JRC.F.3-Chemicals Safety and Alternative Method

Environmental surveillance and in vitro activity of antimicrobial agents against Legionella pneumophila isolated from hospital water systems in Campania, South Italy: a 5-year study.

Abstract Background Legionellosis' treatment failures have been recently reported showing the possibility of resistance development to traditional therapy, especially in healthcare related disease cases. Environmental impact of antibiotic residues, especially in hospital waters, may act on the resistome of Legionella resulting in developing resistance mechanisms. Objectives In this study we investigate the antibiotic susceptibility of environmental Legionella pneumophila (Lpn) strains isolated from hospital water systems in Campania, a region located in Southwest Italy. Methods 5321 hospital water samples were investigated for the presence of Lpn. Among positive samples, antibiotic susceptibility was tested for a random subset of 125 Lpn strains (25 Lpn isolates from each of the following serogroups: 1, 3, 5, 6, 8). Susceptibility testing was performed, using the E-test on buffered charcoal yeast extract agar supplemented with α-ketoglutarate, for 10 antimicrobial drugs: azithromycin, cefotaxime, clarithromycin, doxycycline, erythromycin, rifampicin, tigecycline, ciprofloxacin, levofloxacin and moxifloxacin. Non parametric tests were used to determine and assess the significant differences in susceptibility to the different antimicrobics between the serogroups. Results Among the isolated strains, none showed resistance to the antibiotics tested. Rifampicin was the most active antibiotic against overall Legionella strains, followed by levofloxacin. Between the macrolides the clarithromycin was overall the most active drug, instead the azithromycin was the less active. Analyzing the different serogroups a significant difference was found between serogroup 1 and non-1 serogroup isolates for doxycycline and tigecycline. Conclusions Antibiotic susceptibility of environmental isolates of Legionella spp. might be useful for the early detection of resistance to antibiotics that directly impacts on mortality and length of hospital stay

Global Trends in Marine Plankton Diversity across Kingdoms of Life

35 pages, 18 figures, 1 table, supplementary information https://doi.org/10.1016/j.cell.2019.10.008.-- Raw reads of Tara Oceans are deposited at the European Nucleotide Archive (ENA). In particular, newly released 18S rRNA gene metabarcoding reads are available under the number ENA: PRJEB9737. ENA references for the metagenomics reads corresponding to the size fraction < 0.22 μm (for prokaryotic viruses) analyzed in this study are included in Gregory et al. (2019); see their Table S3. ENA references for the metagenomics reads corresponding to the size fraction 0.22-1.6/3 μm (for prokaryotes and giruses) correspond to Salazar et al. (2019) (see https://zenodo.org/record/3473199). Imaging datasets from the nets are available through the collaborative web application and repository EcoTaxa (Picheral et al., 2017) under the address https://ecotaxa.obs-vlfr.fr/prj/412 for regent data, within the 3 projects https://ecotaxa.obs-vlfr.fr/prj/397, https://ecotaxa.obs-vlfr.fr/prj/398, https://ecotaxa.obs-vlfr.fr/prj/395 for bongo data, and within the 2 projects https://ecotaxa.obs-vlfr.fr/prj/377 and https://ecotaxa.obs-vlfr.fr/prj/378 for WP2 data. A table with Shannon values and multiple samples identifiers, plus a table with flow cytometry data split in six groups are available (https://doi.org/10.17632/p9r9wttjkm.1). Contextual data from the Tara Oceans expedition, including those that are newly released from the Arctic Ocean, are available at https://doi.org/10.1594/PANGAEA.875582The ocean is home to myriad small planktonic organisms that underpin the functioning of marine ecosystems. However, their spatial patterns of diversity and the underlying drivers remain poorly known, precluding projections of their responses to global changes. Here we investigate the latitudinal gradients and global predictors of plankton diversity across archaea, bacteria, eukaryotes, and major virus clades using both molecular and imaging data from Tara Oceans. We show a decline of diversity for most planktonic groups toward the poles, mainly driven by decreasing ocean temperatures. Projections into the future suggest that severe warming of the surface ocean by the end of the 21st century could lead to tropicalization of the diversity of most planktonic groups in temperate and polar regions. These changes may have multiple consequences for marine ecosystem functioning and services and are expected to be particularly significant in key areas for carbon sequestration, fisheries, and marine conservationTara Oceans (which includes both the Tara Oceans and Tara Oceans Polar Circle expeditions) would not exist without the leadership of the Tara Ocean Foundation and the continuous support of 23 institutes (https://oceans.taraexpeditions.org/). We further thank the commitment of the following sponsors: CNRS (in particular Groupement de Recherche GDR3280 and the Research Federation for the Study of Global Ocean Systems Ecology and Evolution FR2022/Tara Oceans-GOSEE), the European Molecular Biology Laboratory (EMBL), Genoscope/CEA, the French Ministry of Research, and the French Government “Investissements d’Avenir” programs OCEANOMICS (ANR-11-BTBR-0008), FRANCE GENOMIQUE (ANR-10-INBS-09-08), MEMO LIFE (ANR-10-LABX-54), the PSL∗ Research University (ANR-11-IDEX-0001-02), as well as EMBRC-France (ANR-10-INBS-02). Funding for the collection and processing of the Tara Oceans data set was provided by NASA Ocean Biology and Biogeochemistry Program under grants NNX11AQ14G, NNX09AU43G, NNX13AE58G, and NNX15AC08G (to the University of Maine); the Canada Excellence research chair on remote sensing of Canada’s new Arctic frontier; and the Canada Foundation for Innovation. We also thank agnès b. and Etienne Bourgois, the Prince Albert II de Monaco Foundation, the Veolia Foundation, Region Bretagne, Lorient Agglomeration, Serge Ferrari, Worldcourier, and KAUST for support and commitment. The global sampling effort was enabled by countless scientists and crew who sampled aboard the Tara from 2009–2013, and we thank MERCATOR-CORIOLIS and ACRI-ST for providing daily satellite data during the expeditions. We are also grateful to the countries who graciously granted sampling permission. We thank Stephanie Henson for providing ocean carbon export data and are also grateful to the other researchers who kindly made their data available. We thank Juan J. Pierella-Karlusich for advice regarding single-copy genes. C.d.V. and N.H. thank the Roscoff Bioinformatics platform ABiMS (http://abims.sb-roscoff.fr) for providing computational resources. C.B. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement 835067) as well as the Radcliffe Institute of Advanced Study at Harvard University for a scholar’s fellowship during the 2016-2017 academic year. M.B.S. thanks the Gordon and Betty Moore Foundation (award 3790) and the National Science Foundation (awards OCE#1536989 and OCE#1829831) as well as the Ohio Supercomputer for computational support. S.G.A. thanks the Spanish Ministry of Economy and Competitiveness (CTM2017-87736-R), and J.M.G. is grateful for project RT2018-101025-B-100. F.L. thanks the Institut Universitaire de France (IUF) as well as the EMBRC platform PIQv for image analysis. M.C.B., D.S., and J.R. received financial support from the French Facility for Global Environment (FFEM) as part of the “Ocean Plankton, Climate and Development” project. M.C.B. also received financial support from the Coordination for the Improvement of Higher Education Personnel of Brazil (CAPES 99999.000487/2016-03)Peer Reviewe

Strategy for the management of diabetic macular edema: the European Vitreo-Retinal Society macular edema study

Objective. To compare the efficacy of different therapies in the treatment of diabetic macular edema (DME). Design. Nonrandomized, multicenter clinical study. Participants. 86 retina specialists from 29 countries provided clinical information on 2,603 patients with macular edema including 870 patients with DME. Methods. Reported data included the type and number of treatment(s) performed, the pre-and posttreatment visual acuities, and other clinical findings.The results were analyzed by the French INSEE (National Institute of Statistics and Economic Studies). Main Outcome Measures. Mean change of visual acuity and mean number of treatments performed. Results.The change in visual acuity over time in response to each treatment was plotted in second order polynomial regression trend lines. Intravitreal triamcinolone monotherapy resulted in some improvement in vision. Treatmentwith threshold or subthreshold grid laser also resulted in minimal vision gain. Anti-VEGF therapy resulted in more significant visual improvement. Treatment with pars plana vitrectomy and internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than that observed with anti-VEGF injection alone. In our DME study, treatment with vitrectomy and ILM peeling alone resulted in the better visual improvement compared to other therapies

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions