Gender differences in health of EU10 and EU15 populations: the double burden of EU10 men

This study compares gender differences in Healthy Life Years (HLY) and unhealthy life years (ULY) between the original (EU15) and new member states (EU10). Based on the number of deaths, population and prevalence of activity limitations from the Statistics of Living and Income Conditions Survey (SILC) survey, we calculated HLY and ULY for the EU10 and EU15 in 2006 with the Sullivan method. We used decomposition analysis to assess the contributions of mortality and disability and age to gender differences in HLY and ULY. HLY at age 15 for women in the EU10 were 3.1 years more than those for men at the same age, whereas HLY did not differ by gender in the EU15. In both populations ULY at age 15 for women exceeded those for men by 5.5 years. Decomposition showed that EU10 women had more HLY because higher disability in women only partially offset (−0.8 years) the effect of lower mortality (+3.9 years). In the EU15 women’s higher disability prevalence almost completely offset women’s lower mortality. The 5.3 fewer ULY in EU10 men than in EU10 women mainly reflected higher male mortality (4.5 years), while the fewer ULY in EU15 men than in EU15 women reflected both higher male mortality (2.9 years) and higher female disability (2.6 years). The absence of a clear gender gap in HLY in the EU15 thus masked important gender differences in mortality and disability. The similar size of the gender gap in ULY in the EU-10 and EU-15 masked the more unfavourable health situation of EU10 men, in particular the much stronger and younger mortality disadvantage in combination with the virtually absent disability advantage below age 65 in men

An NMR-based model to investigate the metabolic phenoreversion of COVID-19 patients throughout a longitudinal study.

After SARS-CoV-2 infection, the molecular phenoreversion of the immunological response and its associated metabolic dysregulation are required for a full recovery of the patient. This process is patient-dependent due to the manifold possibilities induced by virus severity, its phylogenic evolution and the vaccination status of the population. We have here investigated the natural history of COVID-19 disease at the molecular level, characterizing the metabolic and immunological phenoreversion over time in large cohorts of hospitalized severe patients (n = 886) and non-hospitalized recovered patients that self-reported having passed the disease (n = 513). Non-hospitalized recovered patients do not show any metabolic fingerprint associated with the disease or immune alterations. Acute patients are characterized by the metabolic and lipidomic dysregulation that accompanies the exacerbated immunological response, resulting in a slow recovery time with a maximum probability of around 62 days. As a manifestation of the heterogeneity in the metabolic phenoreversion, age and severity become factors that modulate their normalization time which, in turn, correlates with changes in the atherogenesis-associated chemokine MCP-1. Our results are consistent with a model where the slow metabolic normalization in acute patients results in enhanced atherosclerotic risk, in line with the recent observation of an elevated number of cardiovascular episodes found in post-COVID-19 cohorts

Inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection: a prospective cohort study and immunological network analysis

Background HIV-1 mediated dysregulation of the immune response to tuberculosis and its effect on the response to antitubercular therapy (ATT) is incompletely understood. We aimed to analyse the inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection undergoing ATT, with specific focus on the effect of ART and HIV-1 viraemia in those co-infected with HIV-1. Methods In this prospective cohort study and immunological network analysis, a panel of 38 inflammatory markers were measured in the plasma of a prospective patient cohort undergoing ATT at Khayelitsha Site B clinic, Cape Town, South Africa. We recruited patients with sputum Xpert MTB/RIF-positive rifampicin-susceptible pulmonary tuberculosis. Patients were excluded from the primary discovery cohort if they were younger than 18 years, unable to commence ATT for any reason, pregnant, had unknown HIV-1 status, were unable to consent to study participation, were unable to provide baseline sputum samples, had more than three doses of ATT, or were being re-treated for tuberculosis within 6 months of their previous ATT regimen. Plasma samples were collected at baseline (1–5 days after commencing ATT), week 8, and week 20 of ATT. We applied network and multivariate analysis to investigate the dynamic inflammatory profile of these patients in relation to ATT and by HIV status. In addition to the discovery cohort, a validation cohort of patients with HIV-1 admitted to hospital with CD4 counts less than 350 cells per μL and a high clinical suspicion of new tuberculosis were recruited. Findings Between March 1, 2013, and July 31, 2014, we assessed a cohort of 129 participants (55 [43%] female and 74 [57%] male, median age 35·1 years [IQR 30·1–43·7]) and 76 were co-infected with HIV-1. HIV-1 status markedly influenced the inflammatory profile regardless of ATT duration. HIV-1 viral load emerged as a major factor driving differential inflammatory marker expression and having a strong effect on correlation profiles observed in the HIV-1 co-infected group. Interleukin (IL)-17A emerged as a key correlate of HIV-1-induced inflammation during HIV–tuberculosis co-infection. Interpretation Our findings show the effect of HIV-1 co-infection on the complexity of plasma inflammatory profiles in patients with tuberculosis. Through network analysis we identified IL-17A as an important node in HIV–tuberculosis co-infection, thus implicating this cytokine's capacity to correlate with, and regulate, other inflammatory markers. Further mechanistic studies are required to identify specific IL-17A-related inflammatory pathways mediating immunopathology in HIV–tuberculosis co-infection, which could illuminate targets for future host-directed therapies. Funding National Institutes of Health, The Wellcome Trust, UK Research and Innovation, Cancer Research UK, European and Developing Countries Clinical Trials Partnership, and South African Medical Research Council

Policy implementation and priorities to create healthy food environments using the Healthy Food Environment Policy Index (Food-EPI): A pooled level analysis across eleven European countries

Background: Food environments have been recognised as highly influential on population diets. Government policies have great potential to create healthy food environments to promote healthy diets. This study aimed to evaluate food environment policy implementation in European countries and identify priority actions for governments to create healthy food environments. Methods: The Healthy Food Environment Policy Index (Food-EPI) was used to evaluate the level of food environment policy and infrastructure support implementation in Estonia, Finland, Germany, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Slovenia, and Spain in 20192021. Evidence of implementation of food environment policies was compiled in each country and validated by government officials. National experts evaluated the implementation of policies and identified priority recommendations. Findings: Finland had the highest proportion (32%, n = 7/22) of policies shaping food environments with a high level of implementation. Slovenia and Poland had the highest proportion of policies rated at very low implementation (42%, n = 10/24 and 36%, n = 9/25 respectively). Policies regarding food provision, promotion, retail, funding, monitoring, and health in all policies were identified as the most important gaps across the European countries. Experts recommended immediate action on setting standards for nutrients of concern in processed foods, improvement of school food environments, fruit and vegetable subsidies, unhealthy food and beverage taxation, and restrictions on unhealthy food marketing to children. Interpretation: Immediate implementation of policies and infrastructure support that prioritize action towards healthy food environments is urgently required to tackle the burden of obesity and diet-related non-communicable diseases in Europe. Funding: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 774548 and from the Joint Programming Initiative A Healthy Diet for a Healthy Life. (c) 2022 The Author(s

Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC

Seed Regeneration Potential of Canopy Gaps at Early Formation Stage in Temperate Secondary Forests, Northeast China

Promoting the seed regeneration potential of secondary forests undergoing gap disturbances is an important approach for achieving forest restoration and sustainable management. Seedling recruitment from seed banks strongly determines the seed regeneration potential, but the process is poorly understood in the gaps of secondary forests. The objectives of the present study were to evaluate the effects of gap size, seed availability, and environmental conditions on the seed regeneration potential in temperate secondary forests. It was found that gap formation could favor the invasion of more varieties of species in seed banks, but it also could speed up the turnover rate of seed banks leading to lower seed densities. Seeds of the dominant species, Fraxinus rhynchophylla, were transient in soil and there was a minor and discontinuous contribution of the seed bank to its seedling emergence. For Quercus mongolica, emerging seedling number was positively correlated with seed density in gaps (R = 0.32, P<0.01), especially in medium and small gaps (<500 m2). Furthermore, under canopies, there was a positive correlation between seedling number and seed density of Acer mono (R = 0.43, P<0.01). Gap formation could promote seedling emergence of two gap-dependent species (i.e., Q. mongolica and A. mono), but the contribution of seed banks to seedlings was below 10% after gap creation. Soil moisture and temperature were the restrictive factors controlling the seedling emergence from seeds in gaps and under canopies, respectively. Thus, the regeneration potential from seed banks is limited after gap formation

Activation of the Innate Immune Response against DENV in Normal Non-Transformed Human Fibroblasts

In this work, we demonstrate that that both human whole skin and freshly isolated skin fibroblasts are productively infected with Dengue virus (DENV). In addition, primary skin fibroblast cultures were established and subsequently infected with DENV-2; we showed in these cells the presence of the viral antigen NS3, and we found productive viral infection by a conventional plaque assay. Of note, the infectivity rate was almost the same in all the primary cultures analyzed from different donors. The skin fibroblasts infected with DENV-2 underwent signaling through both TLR3 and RIG-1, but not Mda5, triggering up-regulation of IFNβ, TNFα, defensin 5 (HB5) and β defensin 2 (HβD2). In addition, DENV infected fibroblasts showed increased nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3), but not interferon regulatory factor 7 IRF7, when compared with mock-infected fibroblasts. Our data suggest that fibroblasts might even participate producing mediators involved in innate immunity that activate and contribute to the orchestration of the local innate responses. This work is the first evaluating primary skin fibroblast cultures obtained from different humans, assessing both their susceptibility to DENV infection as well as their ability to produce molecules crucial for innate immunity