The emerging importance of lymphatics in health and disease: An NIH workshop report

The lymphatic system (LS) is composed of lymphoid organs and a network of vessels that transport interstitial fluid, antigens, lipids, cholesterol, immune cells, and other materials in the body. Abnormal development or malfunction of the LS has been shown to play a key role in the pathophysiology of many disease states. Thus, improved understanding of the anatomical and molecular characteristics of the LS may provide approaches for disease prevention or treatment. Recent advances harnessing single-cell technologies, clinical imaging, discovery of biomarkers, and computational tools have led to the development of strategies to study the LS. This Review summarizes the outcomes of the NIH workshop entitled Yet to be Charted: Lymphatic System in Health and Disease, held in September 2022, with emphasis on major areas for advancement. International experts showcased the current state of knowledge regarding the LS and highlighted remaining challenges and opportunities to advance the field

Generalized Approach to Translating Exercise Tests and Prescribing Exercise

[EN] Although there is evidence supporting the benefit of regular exercise, and recommendations about exercise and physical activity, the process of individually prescribing exercise following exercise testing is more difficult. Guidelines like % heart rate (HR) reserve (HRR) require an anchoring maximal test and do not always provide a homogenous training experience. When prescribing HR on the basis of % HRR, rating of perceived exertion or Talk Test, cardiovascular/perceptual drift during sustained exercise makes prescription of the actual workload difficult. To overcome this issue, we have demonstrated a strategy for “translating” exercise test responses to steady state exercise training on the basis of % HRR or the Talk Test that appeared adequate for individuals ranging from cardiac patients to athletes. However, these methods depended on the nature of the exercise test details. In this viewpoint, we combine these data with workload expressed as Metabolic Equivalent Task (METs). We demonstrate that there is a regular stepdown between the METs during training to achieve the same degree of homeostatic disturbance during testing. The relationship was linear, was highly-correlated (r = 0.89), and averaged 71.8% (Training METs/Test METs). We conclude that it appears possible to generate a generalized approach to correctly translate exercise test responses to exercise training

IBEX:A versatile multiplex optical imaging approach for deep phenotyping and spatial analysis of cells in complex tissues

The diverse composition of mammalian tissues poses challenges for understanding the cell–cell interactions required for organ homeostasis and how spatial relationships are perturbed during disease. Existing methods such as single-cell genomics, lacking a spatial context, and traditional immunofluorescence, capturing only two to six molecular features, cannot resolve these issues. Imaging technologies have been developed to address these problems, but each possesses limitations that constrain widespread use. Here we report a method that overcomes major impediments to highly multiplex tissue imaging. “Iterative bleaching extends multiplexity” (IBEX) uses an iterative staining and chemical bleaching method to enable high-resolution imaging of >65 parameters in the same tissue section without physical degradation. IBEX can be employed with various types of conventional microscopes and permits use of both commercially available and user-generated antibodies in an “open” system to allow easy adjustment of staining panels based on ongoing marker discovery efforts. We show how IBEX can also be used with amplified staining methods for imaging strongly fixed tissues with limited epitope retention and with oligonucleotide-based staining, allowing potential cross-referencing between flow cytometry, cellular indexing of transcriptomes and epitopes by sequencing, and IBEX analysis of the same tissue. To facilitate data processing, we provide an open-source platform for automated registration of iterative images. IBEX thus represents a technology that can be rapidly integrated into most current laboratory workflows to achieve high-content imaging to reveal the complex cellular landscape of diverse organs and tissues

Regional sociocultural differences as important correlate of physical activity and sedentary behaviour in Swiss preschool children

Regional differences in physical activity in school-aged children and adults even within one country with the same political and health care system have been observed and could not be explained by sociodemographic or individual variables. We analysed whether such differences were already present in preschool children.; Swiss children from 84 childcare centres in five cantons (Aargau, Bern, Fribourg, Vaud, Zurich) comprising about 50% of the population of the country participated. Physical activity was quantified with accelerometers (ActiGraph, wGT3X-BT) and potential correlates were assessed with measurements at the childcare centre or questionnaires. Mixed regression models were used to test associations between potential correlates of total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), light physical activity (LPA) or sedentary behaviour with a special focus on regional differences.; 394 of 476 children (83%) provided valid physical activity data (at least 2 weekdays and 1 weekend day with 10 h recording; mean age 3.9 ± 0.7 years, 54% boys) with 26% and 74% living in the French- and German-speaking parts of Switzerland, respectively. Days consisted of (mean ± standard deviation) 1.5 ± 0.5 h MVPA, 5.0 ± 0.6 h LPA, and 6.3 ± 0.8 h sedentary behaviour with an average of 624 ± 150 counts/min TPA. TPA and MVPA (but not sedentary behaviour or LPA) increased with age, were higher in boys and children with better motor skills. Despite controlling for individual characteristics, familial factors and childcare exposure, children from the French-speaking part of Switzerland showed 13% less TPA, 14% less MVPA, 6% less LPA and 8% more sedentary behaviour than German-speaking children.; Beside motor skills and non-modifiable individual factors, the regional sociocultural difference was the most important correlate of phyical activity and sedentary behaviour. Therefore, regionally adapted public health strategies may be needed

Regional sociocultural differences as important correlate of physical activity and sedentary behaviour in Swiss preschool children

QUESTION: Regional differences in physical activity in school-aged children and adults even within one country with the same political and health care system have been observed and could not be explained by sociodemographic or individual variables. We analysed whether such differences were already present in preschool children. METHODS: Swiss children from 84 childcare centres in five cantons (Aargau, Bern, Fribourg, Vaud, Zurich) comprising about 50% of the population of the country participated. Physical activity was quantified with accelerometers (ActiGraph, wGT3X-BT) and potential correlates were assessed with measurements at the childcare centre or questionnaires. Mixed regression models were used to test associations between potential correlates of total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), light physical activity (LPA) or sedentary behaviour with a special focus on regional differences. RESULTS: 394 of 476 children (83%) provided valid physical activity data (at least 2 weekdays and 1 weekend day with 10 h recording; mean age 3.9 ± 0.7 years, 54% boys) with 26% and 74% living in the French- and German-speaking parts of Switzerland, respectively. Days consisted of (mean ± standard deviation) 1.5 ± 0.5 h MVPA, 5.0 ± 0.6 h LPA, and 6.3 ± 0.8 h sedentary behaviour with an average of 624 ± 150 counts/min TPA. TPA and MVPA (but not sedentary behaviour or LPA) increased with age, were higher in boys and children with better motor skills. Despite controlling for individual characteristics, familial factors and childcare exposure, children from the French-speaking part of Switzerland showed 13% less TPA, 14% less MVPA, 6% less LPA and 8% more sedentary behaviour than German-speaking children. CONCLUSION: Beside motor skills and non-modifiable individual factors, the regional sociocultural difference was the most important correlate of phyical activity and sedentary behaviour. Therefore, regionally adapted public health strategies may be needed

Mapping the lymphatic system across body scales and expertise domains: A report from the 2021 National Heart, Lung, and Blood Institute workshop at the Boston Lymphatic Symposium

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop

Meeting report: 34th international conference on antiviral research

As a result of the multiple gathering and travels restrictions during the SARS-CoV-2 pandemic, the annual meeting of the International Society for Antiviral Research (ISAR), the International Conference on Antiviral Research (ICAR), could not be held in person in 2021. Nonetheless, ISAR successfully organized a remote conference, retaining the most critical aspects of all ICARs, a collegiate gathering of researchers in academia, industry, government and non-governmental institutions working to develop, identify, and evaluate effective antiviral therapy for the benefit of all human beings. This article highlights the 2021 remote meeting, which presented the advances and objectives of antiviral and vaccine discovery, research, and development. The meeting resulted in a dynamic and effective exchange of ideas and information, positively impacting the prompt progress towards new and effective prophylaxis and therapeutics

Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts

Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world