Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development

The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges

Might Heterostyly Underlie Spider Occurrence On Inflorescences? A Case Study Of Palicourea Rigida (rubiaceae), A Common Shrub From Brazilian Cerrado

We carried out a research on the Palicourea rigida (Rubiaceae) inflorescences, a distylous shrub of Brazilian Cerrado. Our objective was to compare the inflorescence architectural complexity and its quality in the two floral morphs and search for any relationship with spider occurrence. In order to assess the quality of inflorescence resources, we quantified the nectar volume and its sugar concentration and the number of fruits and flowers (intact and aborted) for both inflorescence morphs with and without spiders. For the architectural heterogeneity, we quantified floral structures and inflorescence levels of branching. Spider occurrence was higher in longistylous inflorescences than in brevistylous ones. The sampled spiders were classified into the guilds ambushers, jumpers, or orb-weavers. Ambushers, jumpers, and total richness were much higher among longistylous inflorescences. We found no difference between morphs neither in volume or nectar concentration nor in amount of fruits and flowers. However, longistylous inflorescences presented greater architectural heterogeneity than brevistylous ones. Therefore, we suggested that architectural heterogeneity is an important factor underlying the occurrence of cursorial spiders on P. rigida inflorescences, which possibly arose from the relationship between refuge availability and inflorescence architecture. © 2012 Suzana Diniz et al.Foelix, R.F., (1996) Biology of Spiders, , Oxford, UK Oxford University PressRomero, G.Q., Gonzaga, M.O., Santos, A., Japyassú, H.F., Aranhas como agentes de controle biológico em agroecossistemas (2007) Ecologia e Comportamento de Aranhas, pp. 301-315. , Rio de Janeiro, Brazil Editora InterciênciaRomero, G.Q., Souza, J.C., Vasconcellos-Neto, J., Anti-herbivore protection by mutualistic spiders and the role of plant glandular trichomes (2008) Ecology, 89 (11), pp. 3105-3115. , 2-s2.0-63849343303 10.1890/08-0267.1Halaj, J., Ross, D.W., Moldenke, A.R., Importance of habitat structure to the arthropod food-web in Douglas-fir canopies (2000) Oikos, 90 (1), pp. 139-152Nahas, L., Gonzaga, M.O., Del-Claro, K., Emergent Impacts of ant and spiders interactions: Herbivory reduction in a tropical savanna tree (2012) Biotropica, 44 (4), pp. 498-505Teixeira De Souza, A.L., Martins, R.P., Distribution of plant-dwelling spiders: Inflorescences versus vegetative branches (2004) Austral Ecology, 29 (3), pp. 342-349. , DOI 10.1111/j.1442-9993.2004.01371.xDe Souza, A.L.T., Martins, R.P., Foliage density of branches and distribution of plant-dwelling spiders (2005) Biotropica, 37 (3), pp. 416-420. , DOI 10.1111/j.1744-7429.2005.00055.xHatley, C.L., MacMahon, J.A., Spider community organization: Seasonal variation and the role of vegetation architecture (1980) Environmental Entomology, 9, pp. 632-639Evans, T.A., Distribution of social crab spiders in eucalypt forests (1997) Austral Ecology, 22 (1), pp. 107-111. , 2-s2.0-17444414259Balfour, R.A., Rypstra, A.L., The influence of habitat structure on spider density in a no-till soybean agroecosystem (1998) Journal of Arachnology, 26 (2), pp. 221-226. , 2-s2.0-0032219751Raizer, J., Amaral, M.E.C., Does the structural complexity of aquatic macrophytes explain the diversity of associated spider assemblages? (2001) Journal of Arachnology, 29 (2), pp. 227-237. , 2-s2.0-0035538711Scheidler, M., Influence of habitat structure and vegetation architecture on spiders (1990) Zoologischer Anzeiger, 225 (5-6), pp. 333-340. , 2-s2.0-0025527870Denno, R.F., Finke, D.L., Langellotto, G.A., Barbosa, P., Castellanos, I., Direct and indirect effects of vegetation structure and habitat complexity on predator-prey and predator-predator interactions (2005) Ecology of Predator-Prey Interactions, pp. 211-239. , Oxford, UK Oxford University PressNentwig, W., (1993) Spiders of Panama, Flora & Fauna Handbook 12, , Gainesville, Fla, USA Sandhill Crane PressSouza, A.L.T., Gonzaga, M.O., Santos, A., Japyassú, H.F., Influência da estrutura do habitat na distribuição de aranhas (2007) Ecologia e Comportamento de Aranhas, pp. 25-43. , Rio de Janeiro, Brazil Editora InterciênciaChien, S.A., Morse, D.H., The roles of prey and flower quality in the choice of hunting sites by adult male crab spiders Misumena vatia (Araneae, Thomisidae) (1998) Journal of Arachnology, 26 (2), pp. 238-243. , 2-s2.0-0032219748Carlos-Santos, J., Del-Claro, K., Interações entre formigas, herbívoros e nectários extraflorais em Tocoyena formosa (Rubiaceae) em vegetação de cerrado (2001) Revista Brasileira de Zoociências, 3 (1), pp. 77-92Almeida, A.F., Sarmento, F.N.M., (1998) Parque Estadual da Serra de Caldas - Plano de Manejo, , CTE, (Centro Tecnológico de Engenharia Ltda), FEMAGO - Fundação Estadual do Meio Ambiente, Goiânia, BrazilRibeiro, J.F., Walter, B.M.T., Sano, S.M., Almeida, S.P., Fitofisionomias do bioma Cerrado (1998) Cerrado: Ambiente e Flora, pp. 89-166. , EMBRAPA. PlanaltinaRatter, J.A., Bridgewater, S., Ribeiro, J.F., Analysis of the floristic composition of the Brazilian cerrado vegetation III: Comparison of the woody vegetation of 376 areas (2003) Edinburgh Journal of Botany, 60 (1), pp. 57-109. , DOI 10.10M/S0960428603000064MacHado, A.O., (2007) Ções Florais e Heterostilia em Palicourea Rigida (Rubiaceae) Nos Cerrados Do Brasil Central (Master of Science Dissertation) Universidade Federal de Uberlândia, , Uberlândia, BrazilSilva, A.P., (1995) Biologia Reprodutiva e Polinização de Palicourea Rigida H.B.K. (Rubiaceae), , Brasília, Brazil (Master of Science Dissertation), Universidade de BrasíliaShepherd, G.J., (2010) Fitopac 2.1.2.85. Manual Do Usuário, , Campinas, Brazil Departamento de Botânica, Universidade Estadual de CampinasColwell, R.K., http://viceroy.eeb.uconn.edu/estimates/, EstimateS: Statistical estimation of species richness and shared species from samples (Software and User's Guide, Version 7.5, 2005MacArthur, R.H., On the relative abundance of bird species (1957) Proceedings of the National Academy of Sciences of the USA, 43, pp. 293-295Lawton, J.H., Plant architecture and the diversity of phytophagous insects (1983) Annual Review of Entomology, 28, pp. 23-39. , 2-s2.0-0021027010McCoy, E.D., Bell, S.S., Bell, S.S., McCoy, E.D., Mushinsky, R.H., Habitat structure: The evolution and diversifications of a complex topic (1991) Habitat Structure: The Physical Arrangement of Objects in Space, pp. 3-27. , London, UK Chapman & HallFinke, D.L., Denno, R.F., Intraguild predation diminished in complex-structured vegetation: Implications for prey suppression (2002) Ecology, 83 (3), pp. 643-652Finke, D.L., Denno, R.F., Spatial refuge from intraguild predation: Implications for prey suppression and trophic cascades (2006) Oecologia, 149 (2), pp. 265-275. , DOI 10.1007/s00442-006-0443-yHodges, C.M., Optimal foraging in bumblebees: Hunting by expectation (1981) Animal Behaviour, 29 (4), pp. 1166-1171. , 2-s2.0-0000136794Best, L.S., Bierzychudek, P., Pollinator foraging on foxglove (Digitalis purpurea): A test of a new model (1982) Evolution, 36, pp. 70-79Dalby-Ball, G., Meats, A., Effects of fruit abundance within a tree canopy on the behaviour of wild and cultured Queensland fruit flies, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) (2000) Australian Journal of Entomology, 39 (3), pp. 201-207. , DOI 10.1046/j.1440-6055.2000.00167.xMendonca, L.B., Dos Anjos, L., Flower morphology, nectar features, and hummingbird visitation to Palicourea crocea (Rubiaceae) in the Upper Paraná River floodplain, Brazil (2006) Anais da Academia Brasileira de Ciencias, 78 (1), pp. 45-57. , http://www.scielo.br/pdf/aabc/v78n1/a06v78n1.pdfLouda, S.M., Inflorescence spiders: A cost/benefit analysis for the host plant, Haplopappus venetus Blake ( Asteraceae). (1982) Oecologia, 55 (2), pp. 185-191Morse, D.H., (2007) Predator Upon A Flower, Life History and Fitness in A Crab Spider, , London, UK Harvard University PressDel-Claro, K., Berto, V., Réu, W., Effect of herbivore deterrence by ants on the fruit set of an extrafloral nectary plant, Qualea multiflora (Vochysiaceae) (1996) Journal of Tropical Ecology, 12 (6), pp. 887-892. , 2-s2.0-0030417459Wise, D.H., (1993) Spiders in Ecological Webs, , Cambridge, UK Cambridge University PressBreene, R.G., Dean, D.A., Nyffeler, M., Edwards, G.B., (1993) Biology, Predation Ecology, and Significance of Spiders in Texas Cotton Ecosystems with A Key to the Species, , Texas,Tex, USA Texas Agricultural Experiment StationRiechert, S.E., Lockley, T., Spiders as biological control agents (1984) Annual Review of Entomology, 29, pp. 299-320. , 2-s2.0-002157757

New Instruments for Nuclear Astrophysics

A major task in experimental nuclear astrophysics is the measurement of cross sections of capture reactions. In the last years, the astrophysics group of NCSR "Demokritos" developed and used a method for conducting this kind of research using a 4π NaI γ-detector. Of great importance in this method is the determination of the efficiency of the detector, which depends on the average multiplicity of the γ-cascade de-exciting the entry state of the produced nucleus. Two new experimental setups have been studied and are in course of installation at the Tandem Laboratory of the Institute of Nuclear and Particle Physics of NCSR "Demokritos", that will provide the possibility for conducting this kind of experiments inhouse. The first one is a new 14x14 inches NaI detector and the second is the BGO Ball of the GASP setup. These detector setups as well as their potential experimental use will be described in detail

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe