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Abstract Background Heterogeneity in national SARS-CoV-2 infection surveillance capabilities may compromise global enumeration and tracking of COVID-19 cases and deaths and bias analyses of the pandemic’s tolls. Taking account of heterogeneity in data completeness may thus help clarify analyses of the relationship between COVID-19 outcomes and standard preparedness measures. Methods We examined country-level associations of pandemic preparedness capacities inventories, from the Global Health Security (GHS) Index and Joint External Evaluation (JEE), on SARS-CoV-2 infection and COVID-19 death data completion rates adjusted for income. Analyses were stratified by 100, 100–300, 300–500, and 500–700 days after the first reported case in each country. We subsequently reevaluated the relationship of pandemic preparedness on SARS-CoV-2 infection and age-standardized COVID-19 death rates adjusted for cross-country differentials in data completeness during the pre-vaccine era. Results Every 10% increase in the GHS Index was associated with a 14.9% (95% confidence interval 8.34–21.8%) increase in SARS-CoV-2 infection completion rate and a 10.6% (5.91–15.4%) increase in the death completion rate during the entire observation period. Disease prevention (infections: β = 1.08 [1.05–1.10], deaths: β = 1.05 [1.04–1.07]), detection (infections: β = 1.04 [1.01–1.06], deaths: β = 1.03 [1.01–1.05]), response (infections: β = 1.06 [1.00–1.13], deaths: β = 1.05 [1.00–1.10]), health system (infections: β = 1.06 [1.03–1.10], deaths: β = 1.05 [1.03–1.07]), and risk environment (infections: β = 1.27 [1.15–1.41], deaths: β = 1.15 [1.08–1.23]) were associated with both data completeness outcomes. Effect sizes of GHS Index on infection completion (Low income: β = 1.18 [1.04–1.34], Lower Middle income: β = 1.41 [1.16–1.71]) and death completion rates (Low income: β = 1.19 [1.09–1.31], Lower Middle income: β = 1.25 [1.10–1.43]) were largest in LMICs. After adjustment for cross-country differences in data completeness, each 10% increase in the GHS Index was associated with a 13.5% (4.80–21.4%) decrease in SARS-CoV-2 infection rate at 100 days and a 9.10 (1.07–16.5%) decrease at 300 days. For age-standardized COVID-19 death rates, each 10% increase in the GHS Index was with a 15.7% (5.19–25.0%) decrease at 100 days and a 10.3% (− 0.00–19.5%) decrease at 300 days. Conclusions Results support the pre-pandemic hypothesis that countries with greater pandemic preparedness capacities have larger SARS-CoV-2 infection and mortality data completeness rates and lower COVID-19 disease burdens. More high-quality data of COVID-19 impact based on direct measurement are needed.

ObjectiveRheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant pulmonary complication of RA. This study tried to elucidate the mechanisms enhancing inflammation and causing lung injury in RA-ILD, focusing on the role of neutrophil extracellular traps (NETs). The study also investigated the potential benefits of nintedanib in advanced disease.MethodsNine RA-ILD patients and nine healthy controls were included in the study. Inflammatory markers in patients’ circulation were evaluated with immunoassays. The formation of NETs was examined using a citrullinated histone H3 (CitH3) ELISA and cell immunofluorescence. Inflammatory proteins expressed in neutrophils/NETs were studied with real-time qPCR and NET ELISA. To assess the effect of nintedanib, an intracellular tyrosine kinase inhibitor with antifibrotic properties, in RA-ILD a paired study was conducted in five patients before treatment administration and 16 weeks later.ResultsThe soluble terminal complement complex sC5b-9 and the levels of CitH3 were significantly elevated in patients with RA-ILD, compared to healthy controls. In addition, neutrophils isolated from RA-ILD patients released NETs enriched with tissue factor and interleukin-17A. Inflammatory NETs had a dynamic role, increasing the fibrotic potential of human pulmonary fibroblasts (HPFs). On the other hand, nintedanib treatment decreased NETs and sC5b-9 levels in RA-ILD patients.ConclusionThe findings propose an interplay between circulating NETs and HPFs, establishing the immunofibrotic aspects of RA-ILD. They also support the effectiveness of nintedanib in reducing key pathological processes of the disease. Further research is needed to fully understand these mechanisms and optimize treatment strategies for RA-ILD.

: Introduction: As access to effective antiretroviral therapy (ART) has improved globally, tobacco‐related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa. Methods: In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age‐stratified mortality hazard ratios: 1.2−2.3 (females)/1.1−1.9 (males) for people with current versus never smoking status; and 1.0−1.3 (females)/1.0−1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non‐suppression. In sensitivity analysis, we varied smoking‐associated and HIV‐associated mortality risks. Additionally, we estimated the total life‐years gained if a proportion of all virologically suppressed PWH stopped smoking. Results: Forty‐five‐year‐old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life‐years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life‐years. Simulated PWH who continue smoking lose more life‐years from smoking than from HIV (females, 5.3 vs. 3.0 life‐years; males, 3.7 vs. 2.6 life‐years). The impact of smoking and smoking cessation increase as smoking‐associated mortality risks increase and HIV‐associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking‐associated mortality hazard ratio; varying this parameter results in 1.0−5.1 life‐years gained from cessation at age 45y. If 10−25% of virologically suppressed PWH aged 30−59y in South Africa stopped smoking now, 190,000−460,000 life‐years would be gained. Conclusions: Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy., INTRODUCTION South Africa is home to over seven million people with HIV (PWH), more than any other country [1]. Improved access to antiretroviral therapy (ART) has increased life expectancy among [...]

Abstract Introduction As access to effective antiretroviral therapy (ART) has improved globally, tobacco‐related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa. Methods In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age‐stratified mortality hazard ratios: 1.2−2.3 (females)/1.1−1.9 (males) for people with current versus never smoking status; and 1.0−1.3 (females)/1.0−1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non‐suppression. In sensitivity analysis, we varied smoking‐associated and HIV‐associated mortality risks. Additionally, we estimated the total life‐years gained if a proportion of all virologically suppressed PWH stopped smoking. Results Forty‐five‐year‐old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life‐years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life‐years. Simulated PWH who continue smoking lose more life‐years from smoking than from HIV (females, 5.3 vs. 3.0 life‐years; males, 3.7 vs. 2.6 life‐years). The impact of smoking and smoking cessation increase as smoking‐associated mortality risks increase and HIV‐associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking‐associated mortality hazard ratio; varying this parameter results in 1.0−5.1 life‐years gained from cessation at age 45y. If 10−25% of virologically suppressed PWH aged 30−59y in South Africa stopped smoking now, 190,000−460,000 life‐years would be gained. Conclusions Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy.

Abstract Background The rapidly growing burden of non-communicable diseases (NCDs) among people living with HIV in sub-Saharan Africa (SSA) has expanded the number of multidisease models predicting future care needs and health system priorities. Usefulness of these models depends on their ability to replicate real-life data and be readily understood and applied by public health decision-makers; yet existing simulation models of HIV comorbidities are computationally expensive and require large numbers of parameters and long run times, which hinders their utility in resource-constrained settings. Methods We present a novel, user-friendly emulator that can efficiently approximate complex simulators of long-term HIV and NCD outcomes in Africa. We describe how to implement the emulator via a tutorial based on publicly available data from Kenya. Emulator parameters relating to incidence and prevalence of HIV, hypertension and depression were derived from our own agent-based simulation model and other published literature. Gaussian processes were used to fit the emulator to simulator estimates, assuming presence of noise for design points. Bayesian posterior predictive checks and leave-one-out cross validation confirmed the emulator’s descriptive accuracy. Results In this example, our emulator resulted in a 13-fold (95% Confidence Interval (CI): 8–22) improvement in computing time compared to that of more complex chronic disease simulation models. One emulator run took 3.00 seconds (95% CI: 1.65–5.28) on a 64-bit operating system laptop with 8.00 gigabytes (GB) of Random Access Memory (RAM), compared to > 11 hours for 1000 simulator runs on a high-performance computing cluster with 1500 GBs of RAM. Pareto k estimates were 10 year) period, estimate longer-term prevalence of other co-occurring conditions (e.g., postpartum depression among women living with HIV), and project the impact of nationally-prioritized interventions such as national health insurance schemes and differentiated care models.

Sustainability, safety and service life expansion in the construction sector have gained a lot of scientific and technological interest during the last few decades. In this direction, the synthesis and characterization of smart cementitious composites with tailored properties combining mechanical integrity and self-sensing capabilities have been in the spotlight for quite some time now. The key property for the determination of self-sensing behavior is the electrical resistivity and, more specifically, the determination of reversible changes in the electrical resistivity with applied stress, which is known as piezoresistivity. In this study, the mechanical and piezoresistive properties of mortars reinforced with carbon nanotubes (CNTs) and carbon micro-fibers (CMFs) are determined. Silica fume and a polymer with polyalkylene glycol graft chains were used as dispersant agents for the incorporation of the CNTs and CMFs into the cement paste. The mechanical properties of the mortar composites were investigated with respect to their flexural and compressive strength. A four-probe method was used for the estimation of their piezoresistive response. The test outcomes revealed that the combination of the dispersant agents along with a low content of CNTs and CMFs by weight of cement (bwoc) results in the production of a stronger mortar with enhanced mechanical performance and durability. More specifically, there was an increase in flexural and compressive strength of up to 38% and 88%, respectively. Moreover, mortar composites loaded with 0.4% CMF bwoc and 0.05% CNTs bwoc revealed a smooth and reversible change in electrical resistivity vs. compression loading—with unloading comprising a strong indication of self-sensing behavior. This work aims to accelerate progress in the field of material development with structural sensing and electrical actuation via providing a deeper insight into the correlation among cementitious composite preparation, admixture dispersion quality, cementitious composite microstructure and mechanical and self-sensing properties.

Abstract Background Accumulating evidence supports the role of monocytes and neutrophils in radiographic axSpA (r-axSpA). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for both leukocyte lineages and a pro-inflammatory cytokine activating myeloid cells and promoting osteoclastogenesis. It acts through the JAK-STAT pathway. We measured serum GM-CSF and markers of bone metabolism in patients with r-axSpA before and after anti-TNF treatment. Methods Patients with active r-axSpA despite treatment with NSAIDs, all eligible for treatment with a biologic agent, were recruited. Healthy donors were sampled as controls. Serum was collected before (baseline) and after 4–6 months (follow-up) of anti-TNF treatment and the following molecules were measured with ELISA: GM-CSF, sclerostin (SOST), and dickkopf-1 (Dkk-1). Results Twelve r-axSpA patients (7 males, 5 females, median age 37 years) with a median disease duration of 1 year and 16 age- and sex-matched controls were included. At baseline, patients had mean BASDAI 6.3±2 and ASDAS 3.2±0.7, which decreased to 4.1±1.7 and 2.2±0.6 at follow-up, respectively. At baseline, r-axSpA patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, p=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, p=0.001), but similar levels of SOST (369 vs 544pg/ml, p=0.144) compared to controls. Anti-TNF treatment did not affect GM-CSF, Dkk-1, or SOST levels. Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline (r=0.61, p=0.039), while no correlations were identified between bone markers (Dkk-1, SOST) on one hand and GM-CSF or disease activity indices on the other. Conclusions GM-CSF is increased in patients with active AS and strongly correlates with disease activity. TNF inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway responsible for residual inflammation during TNF blockade, but also a potential target of JAK inhibitors, explaining their efficacy in r-axSpA.

Objective: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant pulmonary complication of RA. This study tried to elucidate the mechanisms enhancing inflammation and causing lung injury in RA-ILD, focusing on the role of neutrophil extracellular traps (NETs). The study also investigated the potential benefits of nintedanib in advanced disease. Methods: Nine RA-ILD patients and nine healthy controls were included in the study. Inflammatory markers in patients' circulation were evaluated with immunoassays. The formation of NETs was examined using a citrullinated histone H3 (CitH3) ELISA and cell immunofluorescence. Inflammatory proteins expressed in neutrophils/NETs were studied with real-time qPCR and NET ELISA. To assess the effect of nintedanib, an intracellular tyrosine kinase inhibitor with antifibrotic properties, in RA-ILD a paired study was conducted in five patients before treatment administration and 16 weeks later. Results: The soluble terminal complement complex sC5b-9 and the levels of CitH3 were significantly elevated in patients with RA-ILD, compared to healthy controls. In addition, neutrophils isolated from RA-ILD patients released NETs enriched with tissue factor and interleukin-17A. Inflammatory NETs had a dynamic role, increasing the fibrotic potential of human pulmonary fibroblasts (HPFs). On the other hand, nintedanib treatment decreased NETs and sC5b-9 levels in RA-ILD patients. Conclusion: The findings propose an interplay between circulating NETs and HPFs, establishing the immunofibrotic aspects of RA-ILD. They also support the effectiveness of nintedanib in reducing key pathological processes of the disease. Further research is needed to fully understand these mechanisms and optimize treatment strategies for RA-ILD. [ABSTRACT FROM AUTHOR]

Objective Data Sources Study Design Principal Findings Conclusions What is known on this topic What this study adds To quantify disruptions in hospitalization and ambulatory care throughout the coronavirus disease 2019 (COVID‐19) pandemic for 32 countries, and examine associations of health system characteristics and COVID‐19 response strategies on disruptions.We utilized aggregated inpatient hospitalization and surgical procedure data from the Organization for Economic Co‐operation and Development Health Database from 2010 to 2021. Covariate data were extracted from the Organization for Economic Co‐operation and Development Health Database, World Health Organization, and Oxford COVID‐19 Government Response Tracker.This is a descriptive study using time‐series analyses to quantify the annual effect of the COVID‐19 pandemic on non‐COVID‐19 hospitalizations for 20 diagnostic categories and 15 surgical procedures. We compared expected hospitalizations had the pandemic never occurred in 2020–2021, estimated using autoregressive integrated moving average modeling with data from 2010 to 2019, with observed hospitalizations. Observed‐to‐expected ratios and missed hospitalizations were computed as measures of COVID‐19 impact. Mixed linear models were employed to examine associations between hospitalization observed‐to‐expected ratios and covariates.The COVID‐19 pandemic was associated with 16,300,000 (95% uncertainty interval 14,700,000–17,900,000; 18.0% [16.5%–19.4%]) missed hospitalizations in 2020. Diseases of the respiratory (−2,030,000 [−2,300,000 to −1,780,000]), circulatory (−1,680,000 [−1,960,000 to −1,410,000]), and musculoskeletal (−1,480,000 [−1,720,000 to −1,260,000]) systems contributed most to the declines. In 2021, there were an additional 14,700,000 (95% uncertainty interval 13,100,000–16,400,000; 16.3% [14.9%–17.9%]) missed hospitalizations. Total healthcare workers per capita (β = 1.02 [95% CI 1.00, 1.04]) and insurance coverage (β = 1.05 [1.02, 1.09]) were associated with fewer missed hospitalizations. Stringency index (β = 0.98 [0.98, 0.99]) and excess all‐cause deaths (β = 0.98 [0.96, 0.99]) were associated with more missed hospitalizations.There was marked cross‐country variability in disruptions to hospitalizations and ambulatory care. Certain health system characteristics appeared to be more protective, such as insurance coverage, and number of inputs including healthcare workforce and beds. Substantial disruptions in health services associated with the coronavirus disease 2019 pandemic have placed a renewed interest in health system resilience. While there is a growing body of evidence documenting disruptions in services, there are limited comparative assessments across diverse countries with different health system designs, preparedness levels, and public health responses. Learning and adapting from health system‐specific gaps and challenges highlighted by the pandemic will be critical for improving resilience. All countries experienced disruptions to hospitalizations and surgical procedures with a combined total of 30 million missed hospitalizations and 4 million missed surgical procedures in 2020–2021, but there was marked cross‐country heterogeneity in disruptions. Countries with greater baseline healthcare workers, insurance coverage, and hospital beds had disproportionately lower disruptions in care. National health planning discussions may need to balance health system resiliency and efficiency to avert preventable morbidity and mortality. [ABSTRACT FROM AUTHOR]

Childhood asthma is a chronic inflammatory airway disorder that can drive tissue remodeling. Neutrophils are amongst the most prominent inflammatory cells contributing to disease manifestations and may exert a potent role in the progression of inflammation to fibrosis. However, their role in asthma exacerbation is still understudied. Here, we investigate the association between neutrophil extracellular traps (NETs) and lung fibroblasts in childhood asthma pathophysiology using serum samples from pediatric patients during asthma exacerbation. Cell-based assays and NETs/human fetal lung fibroblast co-cultures were deployed. Increased levels of NETs and interleukin (IL)-17A were detected in the sera of children during asthma exacerbation. The in vitro stimulation of control neutrophils using the sera from pediatric patients during asthma exacerbation resulted in IL-17A-enriched NET formation. The subsequent co-incubation of lung fibroblasts with in vitro-generated IL-17A-enriched NETs led fibroblasts to acquire a pre-fibrotic phenotype, as assessed via enhanced CCN2 expression, migratory/healing capacity, and collagen release. These data uncover the important pathogenic role of the NET/IL-17A axis in asthma exacerbation, linking lung inflammation to fibroblast dysfunction and fibrosis.

Brucellosis is a common zoonotic disease caused by intracellular pathogens of the genus Brucella. Brucella infects macrophages and evades clearance mechanisms, thus resulting in chronic parasitism. Herein, we studied the molecular changes that take place in human brucellosis both in vitro and ex vivo. RNA sequencing was performed in primary human macrophages (Mφ) and polymorphonuclear neutrophils (PMNs) infected with a clinical strain of Brucella spp. We observed a downregulation in the expression of genes involved in host response, such as TNF signaling, IL-1β production, and phagosome formation in Mφ, and phosphatidylinositol signaling and TNF signaling in PMNs, being in line with the ability of the pathogen to survive within phagocytes. Further transcriptomic analysis of isolated peripheral blood mononuclear cells (PBMCs) and PMNs from patients with acute brucellosis before treatment initiation and after successful treatment revealed a positive correlation of the molecular signature of active disease with pathways associated with response to interferons (IFN). We identified 24 common genes that were significantly altered in both PMNs and PBMCs, including genes involved in IFN signaling that were downregulated after treatment in both cell populations, and IL1R1 that was upregulated. The concentration of several inflammatory mediators was measured in the serum of these patients, and levels of IFN-γ, IL-1β and IL-6 were found significantly increased before the treatment of acute brucellosis. An independent cohort of patients with chronic brucellosis also revealed increased levels of IFN-γ during relapse compared to remissions. Taken together, this study provides for the first time an in-depth analysis of the transcriptomic alterations that take place in human phagocytes upon infection, and in peripheral blood immune populations during active disease.

A sustainable Short Food Supply Chain (SFSC) requires collaboration among all actors, which nowadays is facilitated by information and communication technologies (ICT). However, not all SFSC stakeholders network with others in this way, and it is not clear what will draw them to ICT interaction. A simple, user-friendly website, the SMARTCHAIN Innovation Platform, evolving since March 2019, may facilitate interaction and cooperation among SFSC stakeholders. This article presents the Platform's development and evaluates its efficacy and impact by analysing data from Google Analytics (GA) and other sources. Primary Platform features promote communication and information sharing: these are the 1) Innovation Hubs in 9 European countries, 2) Inventories including 150 SFSC innovations and 50 SFSC initiatives, 3) Resources databases of Publications and Weblinks, and 4) Training section. GA showed that visitors to the Platform increased slowly in the 16 months since its start, and the number of page views increased with the amount of time on the Platform. The most visited page of the Platform was the information-providing Innovation Inventory. Most Platform users were in partner countries of the SMARTCHAIN project, but not all Innovation Hubs had high numbers of users. Most users arrived at the Platform by direct link, but LinkedIn was the most important originating social network. Taken together, these data suggest growth potential for an easy-to-use website that provides useful and up-to-date information but little inclination for SFSC stakeholders to use an online Platform for communication.

Sustainability, safety and service life expansion in the construction sector have gained a lot of scientific and technological interest during the last few decades. In this direction, the synthesis and characterization of smart cementitious composites with tailored properties combining mechanical integrity and self-sensing capabilities have been in the spotlight for quite some time now. The key property for the determination of self-sensing behavior is the electrical resistivity and, more specifically, the determination of reversible changes in the electrical resistivity with applied stress, which is known as piezoresistivity. In this study, the mechanical and piezoresistive properties of mortars reinforced with carbon nanotubes (CNTs) and carbon micro-fibers (CMFs) are determined. Silica fume and a polymer with polyalkylene glycol graft chains were used as dispersant agents for the incorporation of the CNTs and CMFs into the cement paste. The mechanical properties of the mortar composites were investigated with respect to their flexural and compressive strength. A four-probe method was used for the estimation of their piezoresistive response. The test outcomes revealed that the combination of the dispersant agents along with a low content of CNTs and CMFs by weight of cement (bwoc) results in the production of a stronger mortar with enhanced mechanical performance and durability. More specifically, there was an increase in flexural and compressive strength of up to 38% and 88%, respectively. Moreover, mortar composites loaded with 0.4% CMF bwoc and 0.05% CNTs bwoc revealed a smooth and reversible change in electrical resistivity vs. compression loading—with unloading comprising a strong indication of self-sensing behavior. This work aims to accelerate progress in the field of material development with structural sensing and electrical actuation via providing a deeper insight into the correlation among cementitious composite preparation, admixture dispersion quality, cementitious composite microstructure and mechanical and self-sensing properties. [ABSTRACT FROM AUTHOR]

Background Several ecologic studies have suggested that the bacillus Calmette-Guérin (BCG) vaccine may be protective against SARS-CoV-2 infection including a highly-cited published pre-print by Miller et al., finding that middle/high- and high-income countries that never had a universal BCG policy experienced higher COVID-19 burden compared to countries that currently have universal BCG vaccination policies. We provide a case study of the limitations of ecologic analyses by evaluating whether these early ecologic findings persisted as the pandemic progressed. Methods Similar to Miller et al., we employed Wilcoxon Rank Sum Tests to compare population medians in COVID-19 mortality, incidence, and mortality-to-incidence ratio between countries with universal BCG policies compared to those that never had such policies. We then computed Pearson’s r correlations to evaluate the association between year of BCG vaccination policy implementation and COVID-19 outcomes. We repeated these analyses for every month in 2020 subsequent to Miller et al.’s March 2020 analysis. Results We found that the differences in COVID-19 burden associated with BCG vaccination policies in March 2020 generally diminished in magnitude and usually lost statistical significance as the pandemic progressed. While six of nine analyses were statistically significant in March, only two were significant by the end of 2020. Discussion These results underscore the need for caution in interpreting ecologic studies, given their inherent methodological limitations, which can be magnified in the context of a rapidly evolving pandemic in which there is measurement error of both exposure and outcome status.

Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TFbearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID- 19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition., Introduction Accumulated clinical evidence during the evolving coronavirus 2019 (COVID-19) pandemic indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers thrombotic complications that affect multiple vital organs, increasing [...]

Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis, leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies, and surgical specimens of abdominal aortic aneurysms (AAAs) from patients with EH were used. Cell-based assays, NETs/human aortic endothelial cell cocultures, and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly diagnosed patients with EH. Stimulation of control neutrophils with plasma from patients with untreated EH generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via an ROS/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced substantially in patients with EH starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAAs. These data reveal the important pathogenic role of an Ang II/ROS/NET/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.

Objectives Management of cardiovascular disease (CVD) is an urgent challenge in low-income and middle-income countries, and interventions may require appraisal of patients’ social networks to guide implementation. The purpose of this study is to determine whether egocentric social network characteristics (SNCs) of patients with chronic disease in western Kenya are associated with overall CVD risk and individual CVD risk factors.Design Cross-sectional analysis of enrollment data (2017–2018) from the Bridging Income Generation with GrouP Integrated Care trial. Non-overlapping trust-only, health advice-only and multiplex (trust and health advice) egocentric social networks were elicited for each participant, and SNCs representing social cohesion were calculated.Setting 24 communities across four counties in western Kenya.Participants Participants (n=2890) were ≥35 years old with diabetes (fasting glucose ≥7 mmol/L) or hypertension.Primary and secondary outcomes We hypothesised that SNCs would be associated with CVD risk status (QRISK3 score). Secondary outcomes were individual CVD risk factors.Results Among the 2890 participants, 2020 (70%) were women, and mean (SD) age was 60.7 (12.1) years. Forty-four per cent of participants had elevated QRISK3 score (≥10%). No relationship was observed between QRISK3 level and SNCs. In unadjusted comparisons, participants with any individuals in their trust network were more likely to report a good than a poor diet (41% vs 21%). SNCs for the trust and multiplex networks accounted for a substantial fraction of variation in measures of dietary quality and physical activity (statistically significant via likelihood ratio test, adjusted for false discovery rate).Conclusion SNCs indicative of social cohesion appear to be associated with individual behavioural CVD risk factors, although not with overall CVD risk score. Understanding how SNCs of patients with chronic diseases relate to modifiable CVD risk factors could help inform network-based interventions.Trial registration number ClinicalTrials.gov identifier: NCT02501746; https://clinicaltrials.gov/ct2/show/NCT02501746.

Spatiotemporal changes over previous decades in grazed Mediterranean landscapes have taken the form of woody plant encroachment in open areas (e.g., grasslands, open shrublands, silvopastoral areas), altering its structure and diversity. Demographic and socioeconomic changes have played a significant role in landscape transformations, mainly by causing the abandonment of traditional management practices such as pastoral activities, wood harvesting, and agricultural practices in marginal lands. This study aimed to quantify and evaluate the spatiotemporal changes in a typical grazed Mediterranean landscape of Mount Zireia during 1945–2020, and to investigate the effect of these changes on the future development (2020–2040) of land use/land cover (LULC) types. Cartographic materials such as aerial orthophotos from 1945, land use maps of 1960, Corine Land Cover of 2018, and recent satellite images were processed with ArcGIS software. To estimate the future projection trends of LULC types, logistic regression analyses were considered in the framework of CLUE modeling. The results indicated that the strongest trend of spatiotemporal changes were forest expansion in open areas, and grasslands reduction, suggesting that the LULC types that were mainly affected were forest, grasslands, and silvopastoral areas. Future development prediction showed that forests will most probably continue to expand over grassland and silvopastoral areas, holding a high dynamic of expansion into abandoned areas. The reduction in grasslands and silvopastoral areas, independent of environment and biodiversity implications, represents a major threat to sustainable livestock husbandry based on natural grazing resources.

Introduction The effect of care environment on orphaned and separated children and adolescents’ (OSCA) mental health is not well characterised in sub-Saharan Africa. We compared the risk of incident post-traumatic stress disorder (PTSD), depression, anxiety and suicidality among OSCA living in Charitable Children’s Institutions (CCIs), family-based care (FBC) and street-connected children and youth (SCY).Methods This prospective cohort followed up OSCA from 300 randomly selected households (FBC), 19 CCIs and 100 SCY in western Kenya from 2009 to 2019. Annual data were collected through standardised assessments. We fit survival regression models to investigate the association between care environment and mental health diagnoses.Results The analysis included 1931 participants: 1069 in FBC, 783 in CCIs and 79 SCY. At baseline, 1004 participants (52%) were male with a mean age (SD) of 13 years (2.37); 54% were double orphans. In adjusted analysis (adjusted HR, AHR), OSCA in CCIs were significantly less likely to be diagnosed with PTSD (AHR 0.69, 95% CI 0.49 to 0.97), depression (AHR 0.48 95% CI 0.24 to 0.97), anxiety (AHR 0.56, 95% CI 0.45 to 0.68) and suicidality (AHR 0.73, 95% CI 0.56 to 0.95) compared with those in FBC. SCY were significantly more likely to be diagnosed with PTSD (AHR 4.52, 95% CI 4.10 to 4.97), depression (AHR 4.72, 95% CI 3.12 to 7.15), anxiety (AHR 4.71, 95% CI 1.56 to 14.26) and suicidality (AHR 3.10, 95% CI 2.14 to 4.48) compared with those in FBC.Conclusion OSCA living in CCIs in this setting were significantly less likely to have incident mental illness, while SCY were significantly more, compared with OSCA in FBC.

# Background This paper investigates the impact of Kenyan unconditional cash transfer programs on a range of HIV risk indicators, including transactional sex, sexual concurrency, knowledge of HIV, and HIV testing. Previous research on cash transfers in similar contexts suggests that the provision of cash transfers can be a potent method to bolster HIV prevention efforts. We hypothesized that as a result of receiving cash transfers from the government, individuals will have increased contact with social services, which can provide them with critical health education that will motivate them to modify their HIV risk behaviors. # Methods We used data from the latest Kenya Demographic and Health Survey (KDHS), which contained 12,800 unique responses from individuals between the ages of 15 and 54. We compared the prevalence of various HIV risk indicators and demographic covariates between those who received cash transfers and those who did not using unequal variances t-tests and chi-square tests. We estimated the average treatment effect on the treated (ATT) using propensity score matching. # Results Notably, individuals who received any cash transfer were less likely to have paid for sex in the past 12 months (ATT: -0.024, _P_=0.023), more likely to know of a place to get tested for HIV (ATT: 0.022, _P_=0.030), and more likely to have used a condom during sex with their most recent partner (ATT: 0.045, _P_=0.038). However, cash transfer recipients were more likely to have a sexual partner 10 or more years older than themselves (ATT: 0.102, _P_

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 μg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 μg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 μg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 μg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 μg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 μg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69–0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68–0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48–8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32–23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.