Dynamics of lymphatic regeneration and flow patterns after lymph node dissection.

Knowledge about the mechanisms of regeneration of the lymphatic vasculature after surgical trauma is essential for the development of strategies for the prevention and therapy of lymphedema. However, little is known about the alterations of lymphatic flow directly after surgical trauma. We investigated lymphatic function in mice using near-infrared imaging for a period of 4 weeks after surgeries that mimic sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), by removal of the popliteal lymph node (LN) alone or together with the popliteal fat pad, respectively. SLNB-like surgery did not cause changes in lymphatic drainage in the majority of cases. In contrast, lymphatic drainage impairment shown by collecting vessel rupture, dermal backflow and rerouting of lymph flow via collateral vessels were observed after ALND-like surgery. All collateral vessels drained to the inguinal LN. These results indicate that less invasive surgery prevents lymphatic decompensation. They also reveal the development and maturation of collateral lymphatic vessels after extensive surgical trauma, which reroute the flow of lymph towards a different LN. These findings might be helpful for the development of strategies to prevent and/or treat post-surgical lymphedema

Compactifications of Heterotic Strings on Non-Kahler Complex Manifolds: II

We continue our study of heterotic compactifications on non-Kahler complex manifolds with torsion. We give further evidence of the consistency of the six-dimensional manifold presented earlier and discuss the anomaly cancellation and possible supergravity description for a generic non-Kahler complex manifold using the newly proposed superpotential. The manifolds studied in our earlier papers had zero Euler characteristics. We construct new examples of non-Kahler complex manifolds with torsion in lower dimensions, that have non-zero Euler characteristics. Some of these examples are constructed from consistent backgrounds in F-theory and therefore are solutions to the string equations of motion. We discuss consistency conditions for compactifications of the heterotic string on smooth non-Kahler manifolds and illustrate how some results well known for Calabi-Yau compactifications, including counting the number of generations, apply to the non-Kahler case. We briefly address various issues regarding possible phenomenological applications.Comment: 106 pages, 8 .eps figures, Harvmac; v2: Some sections expanded, typos corrected and references updated; v3: More typos corrected, one section expanded and references added. Final version to appear in Nucl. Phys.

EpIG‐DB: A database of vascular epiphyte assemblages in the Neotropics

Vascular epiphytes are a diverse and conspicuous component of biodiversity in tropical and subtropical forests. Yet, the patterns and drivers of epiphyte assemblages are poorly studied in comparison with soil‐rooted plants. Current knowledge about diversity patterns of epiphytes mainly stems from local studies or floristic inventories, but this information has not yet been integrated to allow a better understanding of large‐scale distribution patterns. EpIG‐DB, the first database on epiphyte assemblages at the continental scale, resulted from an exhaustive compilation of published and unpublished inventory data from the Neotropics. The current version of EpIG‐DB consists of 463,196 individual epiphytes from 3,005 species, which were collected from a total of 18,148 relevés (host trees and ‘understory’ plots). EpIG‐DB reports the occurrence of ‘true’ epiphytes, hemiepiphytes and nomadic vines, including information on their cover, abundance, frequency and biomass. Most records (97%) correspond to sampled host trees, 76% of them aggregated in forest plots. The data is stored in a TURBOVEG database using the most up‐to‐date checklist of vascular epiphytes. A total of 18 additional fields were created for the standardization of associated data commonly used in epiphyte ecology (e.g. by considering different sampling methods). EpIG‐DB currently covers six major biomes across the whole latitudinal range of epiphytes in the Neotropics but welcomes data globally. This novel database provides, for the first time, unique biodiversity data on epiphytes for the Neotropics and unified guidelines for future collection of epiphyte data. EpIG‐DB will allow exploration of new ways to study the community ecology and biogeography of vascular epiphytes

Suicidal thoughts and depressive feelings amongst Estonian schoolchildren: effect of family relationship and family structure

Depressive feelings and suicidal ideation in a non-clinical sample of adolescents in Estonia were analysed in the context of family structure, mutual relationships amongst family members and schoolchildren's preferences regarding intimate personal contacts with particular family members. Data from the WHO collaborative study 'Health Behaviour in School-aged Children 2005/2006' (HBSC) were used. A representative sample of schoolchildren aged 11, 13 and 15 years completed the semi-structured questionnaire. The analyses included only adolescents living in households with at least one birth parent. The subjects were 4,389 schoolchildren (2,178 boys and 2,211 girls), who were divided into three groups based on: (1) suicidal thoughts, with or without depressive feelings; (2) depressive feelings; and (3) neither suicidal thoughts nor depressive feelings. Multinomial logistic regression was used. The proportion of depressive feelings increased with age for both boys and girls. Girls expressed depressive feelings more frequently than boys from ages 13 and 15 years, and suicidal thoughts from age 15 years. Self-reported satisfaction with relationships in the family reduced the likelihood of depressive feelings and suicidal thoughts. Good communication with the parents reduced the likelihood of suicidal thoughts in all age groups. Adolescents who were satisfied with their family relationships suffered less frequently from depressive feelings and suicidal thoughts. The best environment for an adolescent was a family with both birth parents. Of the adolescents in 'non-intact' families, those with a step-parent in the family showed suicidal thoughts more frequently than those in single-parent families. Associations between family-related variables and suicidal thoughts were significant even after adjusting for family economic deprivation score

Computational Lipidology: Predicting Lipoprotein Density Profiles in Human Blood Plasma

Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond “bad” and “good” cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL), we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile) is calculated. As our main results, we (i) successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii) assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS), revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii) present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia

An RND-Type Efflux System in Borrelia burgdorferi Is Involved in Virulence and Resistance to Antimicrobial Compounds

Borrelia burgdorferi is remarkable for its ability to thrive in widely different environments due to its ability to infect various organisms. In comparison to enteric Gram-negative bacteria, these spirochetes have only a few transmembrane proteins some of which are thought to play a role in solute and nutrient uptake and excretion of toxic substances. Here, we have identified an outer membrane protein, BesC, which is part of a putative export system comprising the components BesA, BesB and BesC. We show that BesC, a TolC homolog, forms channels in planar lipid bilayers and is involved in antibiotic resistance. A besC knockout was unable to establish infection in mice, signifying the importance of this outer membrane channel in the mammalian host. The biophysical properties of BesC could be explained by a model based on the channel-tunnel structure. We have also generated a structural model of the efflux apparatus showing the putative spatial orientation of BesC with respect to the AcrAB homologs BesAB. We believe that our findings will be helpful in unraveling the pathogenic mechanisms of borreliae as well as in developing novel therapeutic agents aiming to block the function of this secretion apparatus

Toward a methodical framework for comprehensively assessing forest multifunctionality

Biodiversity-ecosystem functioning (BEF) research has extended its scope from communities that are short-lived or reshape their structure annually to structurally complex forest ecosystems. The establishment of tree diversity experiments poses specific methodological challenges for assessing the multiple functions provided by forest ecosystems. In particular, methodological inconsistencies and nonstandardized protocols impede the analysis of multifunctionality within, and comparability across the increasing number of tree diversity experiments. By providing an overview on key methods currently applied in one of the largest forest biodiversity experiments, we show how methods differing in scale and simplicity can be combined to retrieve consistent data allowing novel insights into forest ecosystem functioning. Furthermore, we discuss and develop recommendations for the integration and transferability of diverse methodical approaches to present and future forest biodiversity experiments. We identified four principles that should guide basic decisions concerning method selection for tree diversity experiments and forest BEF research: (1) method selection should be directed toward maximizing data density to increase the number of measured variables in each plot. (2) Methods should cover all relevant scales of the experiment to consider scale dependencies of biodiversity effects. (3) The same variable should be evaluated with the same method across space and time for adequate larger-scale and longer-time data analysis and to reduce errors due to changing measurement protocols. (4) Standardized, practical and rapid methods for assessing biodiversity and ecosystem functions should be promoted to increase comparability among forest BEF experiments. We demonstrate that currently available methods provide us with a sophisticated toolbox to improve a synergistic understanding of forest multifunctionality. However, these methods require further adjustment to the specific requirements of structurally complex and long-lived forest ecosystems. By applying methods connecting relevant scales, trophic levels, and above? and belowground ecosystem compartments, knowledge gain from large tree diversity experiments can be optimized

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt