Peripheral Blood Immune Profiling of Convalescent Plasma Donors Reveals Alterations in Specific Immune Subpopulations Even at 2 Months Post SARS-CoV-2 Infection

Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4⁺ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8⁺ regulatory T cells, the highest levels of CD56⁺CD16⁻ NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence.     

Years of good life is a well-being indicator designed to serve research on sustainability

Sustainable development (SD) as popularized by the Brundtland Commission and politically enshrined in the Sustainable Development Goals has been the explicit focus of sustainability science. While there is broad agreement that the trend of human well-being (W) over time should serve as a sustainability criterion, the literature so far has mostly addressed this in terms of its determinants rather than focusing on W itself. There is broad agreement that an indicator for W should have multiple constituents, clearly going beyond gross domestic product. Here, we propose a tailor-made indicator to serve precisely this purpose following a set of specified desiderata, including its applicability to flexibly defined subnational populations by gender, place of residence, ethnicity, and other relevant characteristics. The indicator, years of good life (YoGL), reflects the evident fact that in order to be able to enjoy any quality of life, one has to be alive and thus is primarily based on life expectancy. However, since mere survival is not considered good enough, life years are counted conditional on meeting minimum standards in two dimensions: the objective dimension of capable longevity (consisting of being out of absolute poverty and enjoying minimal levels of physical and cognitive health) and the subjective dimension of overall life satisfaction. We illustrate the calculation of this indicator for countries and subpopulations at different stages of development and with different degrees of data availability.

Sustainability science refers to the most comprehensive scholarly effort to understand the interactions between natural and social systems in order to assess whether certain developmental pathways can be considered sustainable. This should also include the possible negative effects of environmental changes, such as climate change and biodiversity loss, on future human well-being. In this paper, we propose a tailor-made indicator to assess long-term human well-being as the ultimate end of sustainable development. This indicator, called “years of good life” (YoGL), is designed in such a way that it can be both empirically measured—which is the focus of this paper—and modeled in its long-term future trends—which will be the focus of future work.When assessing changes over time in the well-being of certain human populations (or subpopulations, as defined, e.g., by gender, ethnicity, urban/rural place of residence, or other social groupings), one can focus on the determinants or the constituents of well-being. In sustainability science, thus far, empirical and theoretical research has placed more emphasis on studying the determinants, including environmental services (1), whereas specifying its constituents has received less systematic attention, often leaving us with nothing but the unspecific notion of “utility.” The focus on determinants has led to the concept of “inclusive wealth” (IW) which can be used to assess whether a society is on a sustainable development trajectory in terms of the productive base necessary to maintain a high standard of living in the future (2). However, empirically measuring the values and relative effects of the different capitals determining human well-being remains extremely challenging and “no current attempt to date can be said to be fully inclusive” (3).The idea behind YoGL, on the other hand, is to study sustainability by focusing explicitly on the constituents of well-being and its change over time. In doing so, YoGL avoids several of the pitfalls by which the IW approach is plagued (3, 4). For example, rather than making contestable quantitative assessments of the relative contributions of the different determinants of well-being, the demographic approach underlying YoGL provides numerical values of human well-being directly, expressed as the average number of years of good life a person can expect to live as part of a given subpopulation under the conditions of a specified point in time. Based on the assumed universal nature of its unit of measurement—YoGL lived today in one specific population has the same meaning as YoGL lived in the future or in another population—the indicator has a time-independent meaning. This also avoids the pitfalls of specifying a rate at which to discount future well-being, which have become apparent at least since the debates around the Stern report (5). YoGL allows us to directly compare human well-being across different subpopulations and generations. Moreover, while all estimates of the different determinants of future human well-being are highly sensitive to population growth, as a measure referring to per-person well-being the derivation of YoGL is not directly affected by assumptions about the future trajectory of population size. Finally, as stressed by Dasgupta (6), the nature of determinants can change over time and across places depending on different commodities and technological regimes, whereas the constituents of well-being—as used in YoGL—are arguably shared across space and time.In the following, we will first present the proposed design of the indicator. We will then provide a step-by-step user’s guide for empirically deriving YoGL based on the most appropriate available data source, before offering examples of how it can be calculated based on auxiliary information on populations for which the necessary data are not yet fully available. We will close with a discussion and brief outlook as to what is still needed to use this indicator for the assessment of sustainability.     

Imbalance of tissue inhibitors of metalloproteinases (TIMP) – 1 and – 4 serum levels,in patients with inflammatory bowel disease

Background  

Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC).     

Antiatherogenic effect of Pistacia lentiscus via GSH restoration and downregulation of CD36 mRNA expression

Pistacia lentiscus var. Chia (Anacardiaceae) grows almost exclusively on Chios Island, Greece, and gives a resinous exudate resin used for culinary purposes by Mediterranean people. We investigated the molecular mechanisms through which total polar extract of the resin inhibits oxidized low-density lipoprotein (oxLDL) cytotoxic effect on peripheral blood mononuclear cell (PBMC). Cells exposed to oxLDL underwent apoptosis and necrosis, dependent on the duration of exposure. When culturing cells with oxLDL and the polar extract concurrently, we observed inhibition of both the phenomena. Because under oxidative stress the pro-oxidant systems outbalance the antioxidant, potentially producing oxidative damage and ultimately leading to cell death, we measured the levels of intracellular antioxidant glutathione (GSH). Additionally, we measured CD36 expression, a class B scavenger receptor, on CD14-positive cells, as CD36 has been identified as the oxLDL receptor in macrophages and may play a pivotal role in atherosclerotic foam cell formation. oxLDL decreased GSH levels and upregulated CD36 expression. P. lentiscus extract restored GSH levels and downregulated CD36 expression, even at the mRNA level. In order to find out the biologically drastic constituents of the resin's polar extract, fractions derived from RP-HPLC analysis were examined for their antioxidant effect on oxidatively stressed PBMC. The triterpenoid fraction revealed remarkable increase in intracellular GSH. We suggest GSH restoration and downregulation of CD36 mRNA expression as the pathways via which P. lentiscus triterpenes exert antioxidant/antiatherogenic effect. Additionally, our results provide strong evidence of the resin's antiatherogenic effect; therefore it is credited with beneficial health aspects.     

Clinical prediction of normotension in borderline hypertensive men--a 10 year study

OBJECTIVE: To investigate 24-h ambulatory blood pressure measurements (ABPM) as a tool for long-term prediction of future blood pressure (BP) status in high normal and low stage 1 hypertensives. DESIGN, SETTING AND PARTICIPANTS: A total of 165 men from a population screening program with diastolic BP (DBP) 85-94 mmHg and a systolic BP (SBP) < 150 mmHg performed a 24-h ABPM. Ten years later, 120 participants (73%) returned for renewed measurements. MAIN OUTCOME MEASURES: Blood pressure status at 10 years. RESULTS: At the 10-year follow-up, 53% of the participants were classified as hypertensive (HT) (BP > or = 140/90 or taking anti-hypertensive medication) and 47% were classified as normotensive (NT) (BP < 140/90 mmHg). There was no significant baseline differences in office SBP levels between those who were normotensive or hypertensive at follow-up (136/91 versus 138/92 mmHg), whereas both SBP and DBP night-time levels were significantly lower in the future normotensives as compared to the future hypertensives (107/69 versus 112/74 mmHg, P < 0.01). Using recommended normalcy night-time ABP levels of < 120/75 mmHg in addition to office BP (140/90) at baseline, over 85% of the subjects were correctly classified provided they met both clinic and ambulatory night-time criteria for HT and NT classification at baseline. CONCLUSION: The use of ABPM in addition to office BP's in patients with borderline hypertension greatly increases the possibility of identifying those individuals who are at a very small risk of developing future hypertension. This could potentially lead to considerable savings in both patient anxiety, physician time and resource consumption.