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There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidneys active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.

Abstract Background Health systems need tools to assess patient’s experience of service, but existing tools lack reliability and validity assessment. Our aim is to investigate the factor structure, reliability, validity, item parameters and interpretability of the parent version of the Experience of Service Questionnaire (ESQ) for practical use in Greece. Methods A total of 265 caregivers that were using mental health services in Greece participated in this study as part of the Nationwide cross-sectional survey from the Child and Adolescent Mental Health Initiative (CAMHI). Confirmatory Factor Analysis was used to test factor structure. Reliability of all models were measured with omega coefficients. Tobit regression analysis was used to test for convergent and discriminant validity with specifically designed questions. Item parameters were assessed via Item Response Theory. Interpretability was assessed by means of IRT-based scores. Results We found that ESQ is best represented and scored as a unidimensional construct, given potential subscales would not have enough reliability apart from a general factor. Convergent and discriminant validity was demonstrated, as caregivers who perceived that their child benefited from the received mental health care had 6.50 higher summed scores (SMD = 1.14, p

Abstract Background INCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response. Methods All patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website. Discussion With this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP.

Studies on news avoidance rely on a range of theories to explain why news avoidance takes place and its potential consequences, and the debates on different ways of measuring news avoidance have been lively. Despite the numerous approaches and conceptualisations, there is room to theorise what news avoidance entails as a social phenomenon. In this study, we posit that news avoidance can fruitfully be approached as a form of negative social action embedded in a negative social space – a realm of the lifeworld filled with non-doings and non-appearance. We apply this approach, which opens up new questions in the field of news avoidance studies, to a case study of Swedes who opted out of national public service news in the midst of the Covid-19 pandemic. Findings suggest that avoiders of public service news occupy relatively precarious social positions, and that news avoidance is embedded in a broader negative social space.

Carbon quantum dots (CQDs) are an emerging type of multifunctional nanomaterial. They have unique optical and electronic properties based on their quantum size effect and limiting effect. The carbon quantum dot prepared from biomass is green and environmentally friendly, and it can also achieve a high comprehensive utilization of undervalued biomass wastes. Biomass carbon quantum dots with abundant surface functional groups and good biocompatibility show great potential in ion detection and bioimaging. This review paper focuses on the synthesis methods of CQDs from biomass and the perspective of their applications in recent years, as well as the challenges in the future.

Abstract This work deals with promoting the efficiency of removing the cationic and ionic dyes by new aerogel–carbon nanostructures. For cleaner production the rice straw-pulping black liquors, which regards serious environmental risk during routine disposing, is used in preparing the aerogel precursors. These aerogels (AGBs) depend on using pulping black liquor in hybrid with resorcinol and the less carcinogenic formaldehyde butyraldehyde. Black liquors from five pulping processes are used, Elemental, thermogravimetric (TGA and DTG), and FTIR-ATR analyses are used to characterize the carbon precursors. While their adsorption behavior toward cationic and anionic dyes are accessed via iodine-value, adsorption capacity and kinetic models, textural characterization, and SEM. The TGA measurements reveal that AGBs from BLs of neutral sulfite and soda-borohydride pulping reagents have higher activation and degradation energies than other aerogels. In terms of cationic and anionic dyes adsorption as well as textural characterization, the AGB-CNSs surpass that made from BLs. The discarded KOH/NH4OH black liquor is used to synthesize the best aerogel precursor for producing cationic methylene blue dye (MB) adsorbent, where it provides an adsorption capacity 242.1 mg/g. The maximum anionic brilliant blue dye (BB) adsorption capacity, 162.6 mg/g, is noticed by Kraft BL-aerogel-CNSs. These finding data overcome the literature carbon adsorbents based on lignin precursors. All examined CNSs toward MB dye follow the Langmuir adsorption equilibrium; while primarily the Freundlich model for BB dye. The pseudo-second-order kinetic model well fits the adsorption kinetics of investigated AGB-CNSs. The textural characterization and SEM revealed a mixture of mesoporous and micro porous features in the CNSs.

Abstract Intense exercise leads to increased production of free radicals, resulting in an inflammatory response in athletes. For this reason, it was decided to investigate whether a single intensive exercise until exhaustion applied after a 2-week rest period would result in a violation of the pro-oxidant-antioxidant balance. Twenty-seven trained female basketball players (age: 16.55 ± 0.96 years, body mass: 66.40 ± 13.68 kg, height: 173.45 ± 5.14 cm) were enrolled to the study following the application of inclusion and exclusion criteria. Study was conducted at the end of the competitive training phase. Participants underwent incremental treadmill exercise, with blood samples collected before the test, immediately post-exercise, and after a 3-h restitution period. Total antioxidant capacity (TAC) levels increased significantly after exercise and remained unchanged after 3 h. Concentration of interleukin-10 (IL-10) and creatine kinase (CK) significantly increased after exercise and then decreased. Concentration of interleukin-2 (IL-2) was significantly reduced immediately and 3 h after exercise, while interleukin-13 (IL-13), interleukin-1α (IL-1α), and tryptophan (TRP) decreased 3 h after exercise. No significant changes were observed in other biochemical parameters. Obtained results show an increased antioxidant capacity which reduced oxidative stress and inflammation in response to intense exercise indicating that rested athletes have a high adaptation and elevated tolerance to effort.

Hypersensitivity pneumonitis (HP) represents the third common interstitial lung disease caused by an exaggerated immune response following the inhalation of organic and/or chemical environmental antigens. The aim of this study was to determine the cut-off values of specific IgG antibodies (named precipitins) and their association with clinical data in the diagnosis of HP. In this 10-year retrospective study, the IgG concentrations against six antigens, Penicillium chrysogenum/notatum, Aspergillus fumigatus, Alternaria alternata, Aspergillus niger, Micropolyspora faeni, and pigeon droppings, were retrieved. The controlled group was made of 1516 healthy subjects without diagnosis of lung pathologies, while the case group consisted of 54 individuals affected by HP. Considering all six IgG antibodies together and the 97.5% percentiles determined in the control group, 30 of 54 subjects (56%) had one or more positive precipitins. In these patients, the major frequencies found were IgG antibodies against pigeon droppings, followed by Penicillium chrysogenum/notatum and Aspergillus niger. Although the sensitivity of serum precipitins depends on the population enrolled and the method used, the cut-off values determined in this study can be a valuable tool for clinicians in the diagnosis of HP, in eliminating the antigens responsible from the environment, and in establishing more specific IgG panels.

Objective . To determine clinical presentations and laboratory findings of meningitis outbreak among children in 2023 in Iraq. Method . the demographic data (gender, age, symptoms, and disease transmission among family members) were collected from child patients, who were admitted to Halabja and Sulaimania pediatric teaching hospital in the period of 15 March 2023 to 1st of August, 2023. The blood and cerebrospinal fluid (CSF) specimens were collected for hematological, biochemical, microscopic, and microbiological examinations, including culturing and FilmArray meningitis/encephalitis panel. Results . The population studied were 170 children between 1 and 18 years old, Males were 110 (64.7%), and females were 60 (35.3%). Children between 5 and 10 years old had the highest frequency, whereas only 2 children were 1000 leucocytes/µ, followed by 31.2% for those who had

Summary: Pollution, causing millions of deaths annually, disproportionally affects low- and middle-income countries (LMICs). Mercury ranks among the three main chemicals of major public health concern, and even low levels can cause cardiovascular and nervous outcomes, with children and indigenous populations being especially vulnerable. Nearly 80% of all emissions in South America originate from the Amazon. Brazil, the fifth-largest contributor to global mercury emissions, exemplifies the challenges faced by LMICs in effectively monitoring and addressing mercury exposure/intoxication. Despite having powerful tools such as SINAN (a digital platform for compulsory disease reporting), and Community Health Agents, data reveals significant underreporting, especially in the Amazon. Furthermore, SINAN has important delays in its update: for instance, 196 cases of Munduruku Indigenous people in 2019 have only been included in 2023. In this Personal View, we outline insightful recommendations to enhance public health surveillance and implement enduring, effective strategies to monitor, report and address mercury exposure/intoxication, focusing on the Brazilian Amazon. Although these recommendations are tailored to the challenges of this country, they hold potential for adaptation by other Amazonian countries facing similar issues (high mercury emissions and the presence of vulnerable populations, among others).

Anthropogenic activities have left a legacy of contaminated vacant land, which disproportionately affects lower income communities and can have detrimental impacts on human health, particularly children. A management solution is needed to address this widespread lead contamination in urban soils of vacant lots. In this study, high-Fe biosolids incinerator ash (BIA) was evaluated for its ability to sequester soil Pb. Five blends were created using BIA and different amount of other products (dredge, biosolids compost, and yard waste compost) to determine the most effective treatment to reduce Pb bioaccessibility in the soil. The sorption capacity of the BIA for Pb was evaluated by mixing the BIA with Pb(NO3)2 at 1000 to 100,000 ​mg ​Pb/kg BIA. The contaminated soil from Cleveland, OH was treated with five BIA-based blends at a 1:1 (w/w) ratio, and Pb bioaccessibility was evaluated using USEPA Method 1340 ​at pH 2.5 and the Physiologically Based Extraction Test (PBET) at pH 2.5. BIA was a strong sorbent for Pb, sorbing ∼100% of the Pb from solution at 10,000 ​mg/L with only 41% bioaccessibility based on Method 1340 ​at pH 2.5. The blend containing 4.5%, 10%, or 19% BIA reduced the Pb bioaccessibility by 48% from the control based on both bioaccessibility methods. The bioaccessible Pb determined by PBET was less than that by USEPA Method 1340 ​at pH 2.5. However, similar reductions in bioaccessible Pb between blend-treated soils and the unamended soil were observed for all bioaccessibility methods. Plant growth assays showed the blends to have little to no significant impact on clover growth, mortality, or flower production, with the blend containing 10% BIA showing greater biomass yield. Results showed BIA-based blends were able to reduce bioaccessible Pb in the soil. This remediation approach may improve the urban living environment and protects public health.

BackgroundBronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.Research questionIs consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD?Study design and methodsWe retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEV1 (FEV1-BDR), change in FVC (FVC-BDR), and change in in FEV1, FVC or both (ATS-BDR). Using generalized linear models adjusted for demographics, smoking history, FEV1 % predicted after bronchodilator administration, and number of visits that the participant completed, we assessed the association of BDR group: (1) consistent BDR, (2) inconsistent BDR, and (3) never BDR with asthma, CT scan features, blood eosinophil levels, and FEV1 decline in participants without COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) and the entire cohort (participants with or without COPD).ResultsBoth consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEV1-BDR and FVC-BDR definitions. Eosinophils did not vary consistently among BDR groups. Consistent BDR was associated with FEV1 decline over time relative to never BDR in the entire cohort. In participants with GOLD stage 0 disease, both the inconsistent ATS-BDR group (OR, 3.20; 95% CI, 2.21-4.66; P < .001) and consistent ATS-BDR group (OR, 9.48; 95% CI, 3.77-29.12; P < .001) were associated with progression to COPD relative to the never ATS-BDR group.InterpretationDemonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease.

Abstract Background Influenza vaccination is recommended for those at increased risk of influenza complications and their household contacts to help reduce influenza exposure. Adults who require care often experience health issues that could increase the risk of severe influenza and have close contact with caregivers. Assessing influenza vaccination prevalence in caregivers and care recipients can provide important information about uptake. Objectives We aimed to (1) estimate influenza non-vaccination prevalence and (2) assess factors associated with non-vaccination among caregivers aged ≥ 45 years and among care recipients aged ≥ 65 years. Methods We conducted an analysis of cross-sectional data from the Canadian Longitudinal Study on Aging collected 2015–2018. We estimated non-vaccination prevalence and reported adjusted odds ratios with 95% confidence intervals from logistic regression models to identify factors associated with non-vaccination among caregivers and care recipients. Results Of the 23,500 CLSA participants who reported providing care, 41.4% (95% CI: 40.8%, 42.0%) reported not receiving influenza vaccine in the previous 12 months. Among the 5,559 participants who reported receiving professional or non-professional care, 24.8% (95% CI: 23.7%, 26.0%) reported not receiving influenza vaccine during the same period. For both groups, the odds of non-vaccination were higher for those who had not visited a family doctor in the past year, were daily smokers, and those who identified as non-white. Discussion Identifying groups at high risk of severe influenza and their close contacts can inform public health efforts to reduce the risk of influenza. Our results suggest sub-optimal influenza vaccination uptake among caregivers and care recipients. Efforts are needed to increase influenza vaccination and highlight the direct and indirect benefits for caregiver-care recipient pairs. Conclusion The proportions of both caregivers and care recipients who had not been vaccinated for influenza was high, despite the benefits of vaccination. Influenza vaccination campaigns could target undervaccinated, high-risk groups to increase coverage.

Background and aimsColon cancer can occur sporadically or in the setting of chronic inflammation, such as in patients with inflammatory bowel disease. We previously showed that A20, a critical negative regulator of tumor necrosis factor signal transduction, could regulate sporadic colon cancer development. In this report, we investigate whether A20 also acts as a tumor suppressor in a model of colitis-associated cancer.MethodsColitis and colitis-associated tumors were induced in wild-type and A20 intestinal epithelial cell-specific knockout (A20dIEC) mice using dextran sodium sulfate and azoxymethane. Clinicopathologic markers of inflammation were assessed in conjunction with colonic tumor burden. Gene expression analyses and immunohistochemistry were performed on colonic tissue and intestinal enteroids. Nitric oxide (NO) production and activity were assessed in whole colonic lysates and mouse embryonic fibroblasts.ResultsA20dIEC mice develop larger tumors after treatment with dextran sodium sulfate and azoxymethane than wild-type mice. In addition to elevated markers of inflammation, A20dIEC mice have significantly enhanced expression of inducible nitric oxide synthase (iNOS), a well-known driver of neoplasia. Enhanced iNOS expression is associated with the formation of reactive nitrogen species and DNA damage. Loss of A20 also enhances NO-dependent cell death directly.ConclusionMechanistically, we propose that A20 normally restricts tumor necrosis factor-induced nuclear factor kappa B-dependent production of iNOS in intestinal epithelial cells, thereby protecting against colitis-associated tumorigenesis. We also propose that A20 plays a direct role in regulating NO-dependent cell death.

Mine lands contaminted with heavy metals pose environmental risks, and thus reclamation is paramount for improving soil, plant, animal, and ecosystem health. A metal-contaminated alluvial mine tailing, devoid of vegetation, received 224 ​Mg ​ha−1 of both lime and biosolids in 1998, and long-term reclamation success was quantified in 2019 with respect to soils, plants, and linkages to animals. Reclamation success was quantified using the Soil Management Assessment Framework (SMAF), in conjunction with bioavailable (0.01 ​M CaCl2 extractable) and plant-available (Mehlich-3 extractable) soil metal concentrations, X-ray absorption spectroscopy, plant metal concentrations, and plant quality characteristics. Results showed that all soil indicators were improved in successfully-reclaimed areas as compared to on-site degraded areas, including increases in soil aggregate stability, pH, plant-available P and K, soil organic C, potentially-mineralizable N, microbial biomass C and β-glucosidase activity and decreases in soil bulk density and electrical conductivity. Of indicators, unitless soil health scores were assigned based on the SMAF, with data suggesting that bulk density, wet aggregate stability, potentially- mineralizable N, microbial biomass C, pH, and electrical conductivity should be monitored in the future. The long-term effects of lime and biosolids application have improved soil physical, biological, and overall soil health. Plant metal concentrations have decreased by an order of magnitude since early reclamation, with most plant metal concentrations being tolerable for domestic livestock consumption. From an animal health perspective, feeding grasses from this site during latter parts of a growing season may need supplemental feed to provide greater protein and energy content, and to reduce potentially-harmful Cd concentrations from food chain bioaccumulation. However, a health concern exists based on soil bioavailable Cd and Zn concentrations that exceed ecological soil screening levels. Still, plants have stabilized the soil and acidity remains neutralized, leading to long-term improvements in soil health, with overall improved ecosystem health.

While the scholarship on the role capitalism played in the genesis of nationalism is relatively coherent, our understanding of the relationship between those two phenomena once they have emerged is much more disjointed. Are capitalism and nationalism inherently conflictual or is their relationship a symbiotic one? Under what conditions is one of those two patterns more likely? Clues about this dimension of the link between capitalism and nationalism are not readily available in existing accounts of either phenomenon. The goal of this article, therefore, is to cull and systematize various strands of ideas about how these two phenomena might be connected.

Amongst the range of bioprinting technologies currently available, bioprinting by material extrusion is gaining increasing popularity due to accessibility, low cost, and the absence of energy sources, such as lasers, which may significantly damage the cells. New applications of extrusion-based bioprinting are systematically emerging in the biomedical field in relation to tissue and organ fabrication. Extrusion-based bioprinting presents a series of specific challenges in relation to achievable resolutions, accuracy and speed. Resolution and accuracy in particular are of paramount importance for the realization of microstructures (for example, vascularization) within tissues and organs. Another major theme of research is cell survival and functional preservation, as extruded bioinks have cells subjected to considerable shear stresses as they travel through the extrusion apparatus. Here, an overview of the main available extrusion-based printing technologies and related families of bioprinting materials (bioinks) is provided. The main challenges related to achieving resolution and accuracy whilst assuring cell viability and function are discussed in relation to specific application contexts in the field of tissue and organ fabrication.