Humoral profiling of pediatric patients with cancer reveals robust immunity following anti-SARS-CoV-2 vaccination superior to natural infection.

BACKGROUND: Pediatric patients with cancer infected with COVID-19 may be at higher risk of severe disease and may be unable to mount an adequate response to the virus due to compromised immunity secondary to their cancer therapy. PROCEDURE: This study presents immunologic analyses of 20 pediatric patients with cancer, on active chemotherapy or having previously received chemotherapy, and measures their immunoglobulin titers and activation of cellular immunity response to acute SARS-CoV-2 infection and COVID-19 vaccination compared with healthy pediatric controls. RESULTS: Forty-three patients were enrolled, of which 10 were actively receiving chemotherapy, 10 had previously received chemotherapy, and 23 were healthy controls. Pediatric patients with cancer had similar immunoglobulin titers, antibody binding capacity, and effector function assay activity after vaccination against COVID-19 compared with healthy controls, though more variability in response was noted in the cohort actively receiving chemotherapy. Compared with acute infection, vaccination against COVID-19 produced superior immunoglobulin responses, particularly IgA1, IgG1, and IgG3, and elicited superior binding capacity and effector function in children with cancer and healthy controls. CONCLUSIONS: Pediatric patients receiving chemotherapy and those who had previously received chemotherapy had adequate immune activation after both vaccination and acute infection compared to healthy pediatric controls, although there was a demonstrated variability in response for the patients on active chemotherapy. Vaccination against COVID-19 produced superior immune responses compared to acute SARS-CoV-2 infection in pediatric patients with cancer and healthy children, underscoring the importance of vaccination even in previously infected individuals.

Heterogeneity in the evaluation of suspected MIS-C: a cross-sectional vignette-based survey.

BACKGROUND AND OBJECTIVES: Multisystem Inflammatory Syndrome in Children (MIS-C) is an emerging complication of COVID-19 which lacks a definitive diagnostic test and evidence-based guidelines for workup. We sought to assess practitioners' preferences when initiating a workup for pediatric patients presenting with symptoms concerning for MIS-C. METHODS: In a cross-sectional vignette-based survey, providers were presented with clinical vignettes of a patient presenting with 24 h of fever from a community with high rates of COVID-19. Respondents were asked about their general practices in pursuing a workup for potential MIS-C including testing obtained, criteria for diagnosis, and timing to confirm or rule out the diagnosis. RESULTS: Most of the 174 respondents were physicians from the United States at academic medical centers. The majority of providers would not initiate MIS-C workup for fever and non-specific symptoms unless the fever lasted more than 72 h. Skin rash, abdominal pain, and shortness of breath were symptoms that raised greatest concern for MIS-C. Most providers would obtain COVID-19 PCR or antigen testing, plus blood work, in the initial workup. The list of laboratory studies providers would obtain is extensive. Providers primarily rely on cardiac involvement to confirm a MIS-C diagnosis, and establishing a diagnosis takes 24-48 h. CONCLUSIONS: Significant heterogeneity exists amongst providers as to when to initiate the MIS-C workup, the order and content of the workup, and how to definitively diagnose MIS-C. A diagnostic test with high sensitivity and specificity for MIS-C and refined evidence-based guidelines are needed to expedite diagnosis and treatment.

Pediatric biorepository participation during the COVID-19 pandemic: predictors of enrollment and biospecimen donation.

BACKGROUND: Patient-level predictors of enrollment in pediatric biorepositories are poorly described. Especially in pandemic settings, understanding who is likely to enroll in a biorepository is critical to interpreting analyses conducted on biospecimens. We describe predictors of pediatric COVID-19 biorepository enrollment and biospecimen donation to identify gaps in COVID-19 research on pediatric biospecimens. METHODS: We compared data from enrollees and non-enrollees aged 0-25 years with suspected or confirmed COVID-19 infection who were approached for enrollment in the Massachusetts General Hospital pediatric COVID-19 biorepository between April 12, 2020, and May 28, 2020, from community or academic outpatient or inpatient settings. Demographic and clinical data at presentation to care were from automatic and manual chart extractions. Predictors of enrollment and biospecimen donation were assessed with Poisson regression models. RESULTS: Among 457 individuals approached, 214 (47%) enrolled in the biorepository. A COVID-19 epidemiologic risk factor was recorded for 53%, and 15% lived in a US Centers for Disease Control and Prevention-defined COVID-19 hotspot. Individuals living in a COVID-19 hotspot (relative risk (RR) 2.4 [95% confidence interval (CI): 1.8-3.2]), with symptoms at presentation (RR 1.8 [95% CI: 1.2-2.7]), or admitted to hospital (RR 1.8 [95% CI: 1.2-2.8]) were more likely to enroll. Seventy-nine percent of enrollees donated any biospecimen, including 97 nasopharyngeal swabs, 119 oropharyngeal swabs, and 105 blood, 16 urine, and 16 stool specimens, respectively. Age, sex, race, ethnicity, and neighborhood-level socioeconomic status based on zip code did not predict enrollment or biospecimen donation. CONCLUSIONS: While fewer than half of individuals approached consented to participate in the pediatric biorepository, enrollment appeared to be representative of children affected by the pandemic. Living in a COVID-19 hotspot, symptoms at presentation to care and hospital admission predicted biorepository enrollment. Once enrolled, most individuals donated a biospecimen.

Virologic Features of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children.

BACKGROUND: Data on pediatric coronavirus disease 2019 (COVID-19) has lagged behind adults throughout the pandemic. An understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics in children would enable data-driven public health guidance. METHODS: Respiratory swabs were collected from children with COVID-19. Viral load was quantified by reverse-transcription polymerase chain reaction (RT-PCR); viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences. RESULTS: One hundred ten children with COVID-19 (median age, 10 years [range, 2 weeks-21 years]) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first 5 days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified. CONCLUSIONS: Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.

The impact of yoga on aging physiology: A review.

Frailty represents diminished reserve across multiple physiologic systems, accompanied by increased vulnerability to stressors and increased morbidity and mortality. With population aging, strategies to prevent and manage frailty are priorities in clinical medicine and public health. Current evidence-based approaches to frailty management are multimodal in nature. Yoga, an increasingly popular and highly adaptable mind-body practice, is multi-component, incorporating physical postures, breathing practices, meditation, and other elements, and may be a strategy for frailty management. Here, we summarize the evidence linking yoga practice to mitigation of age-related degradation across multiple physiologic systems, including cardiovascular, pulmonary, musculoskeletal, and nervous systems. We discuss putative mechanisms of action including modulation of the hypothalamic-pituitary-adrenal axis. Finally, we consider implications for clinical practice and future research.

The potential of Hungarian bauxite residue isolates for biotechnological applications.

Bauxite residue (red mud) is considered an extremely alkaline and salty environment for the biota. We present the first attempt to isolate, identify and characterise microbes from Hungarian bauxite residues. Four identified bacterial strains belonged to the Bacilli class, one each to the Actinomycetia, Gammaproteobacteria, and Betaproteobacteria classes, and two to the Alphaproteobacteria class. All three identified fungi strains belonged to the Ascomycota division. Most strains tolerated pH 8-10 and salt content at 5-7% NaCl concentration. Alkalihalobacillus pseudofirmus BRHUB7 and Robertmurraya beringensis BRHUB9 can be considered halophilic and alkalitolerant. Priestia aryabhattai BRHUB2, Penicillium chrysogenum BRHUF1 and Aspergillus sp. BRHUF2 are halo- and alkalitolerant strains. Most strains produced siderophores and extracellular polymeric substances, could mobilise phosphorous, and were cellulose degraders. These strains and their enzymes are possible candidates for biotechnological applications in processes requiring extreme conditions, e.g. bioleaching of critical raw materials and rehabilitation of alkaline waste deposits.

Ecotoxicity attenuation by acid-resistant nanofiltration in scandium recovery from TiO2 production waste.

The lack of high-grade scandium (Sc) ores and recovery strategies has stimulated research on the exploitation of non-ore-related secondary sources that have great potential to safeguard the critical raw materials supply of the EU's economy. Waste materials may satisfy the growing global Sc demand, specifically residues from titanium dioxide (TiO2) production. New technologies are being developed for the recovery of Sc from such residues; however, the possible environmental impacts of intermediary products and residues are usually not considered. In order to provide a comprehensive ecotoxicity characterisation of the wastes and intermediate residues resulting from one promising new technology, acid-resistant nanofiltration (arNF), a waste-specific ecotoxicity toolkit was established. Three ecotoxicity assays were selected with specific test parameters providing the most diverse outcome for toxicity characterisation at different trophic levels: Aliivibrio fischeri (bacteria) bioluminescence inhibition (30 min exposure), Daphnia magna (crustacean) lethality and immobilisation (24 h exposure) and Lemna minor (plant) growth inhibition with determination of the frond number (7 d exposure). According to our results, the environmental impact of the generated intermediate and final residues on the aquatic ecosystem was mitigated by the consecutive steps of the filtration methods applied. High and statistically significant toxicity attenuation was achieved according to each test organism: toxicity was lowered based on EC20 values, according to the A. fischeri bioluminescence inhibition assay (by 97%), D. magna lethality (by 99%) and L. minor frond number (by 100%), respectively, after the final filtration step, nanofiltration, in comparison to the original waste. Our results underline the importance of assessing chemical technologies' ecotoxicological and environmental impacts with easy-to-apply and cost-effective test methods to showcase the best available technologies.

A re-analysis of NH4+ sorption on biochar: Have expectations been too high?

Sorption of nutrients such as NH4+ is often quoted as a critical property of biochar, explaining its value as a soil amendment and a filter material. However, published values for NH4+ sorption to biochar vary by more than 3 orders of magnitude, without consensus as to the source of this variability. This lack of understanding greatly limits our ability to use quantitative sorption measurements towards product design. Here, our objective was to conduct a quantitative analysis of the sources of variability, and infer which biochar traits are more favourable to high sorption capacity. To do so, we conducted a standardized remodelling exercise of published batch sorption studies using Langmuir sorption isotherm. We excluded studies presenting datasets that either could not be reconciled with the standard Langmuir sorption isotherm or generated clear outliers. Our analysis indicates that the magnitude of sorption capacity of unmodified biochar for NH4+ is lower than previously reported, with a median of 4.2 mg NH4+ g-1 and a maximum reported sorption capacity of 22.8 mg NH4+ g-1. Activation resulted in a significant relative improvement in sorption capacity, but absolute improvements remain modest, with a maximum reported sorption of 27.56 mg NH4+ g-1 for an activated biochar. Methodology appeared to substantially impact sorption estimates, especially practices such as pH control of batch sorption solution and ash removal. Our results highlight some significant challenges in the quantification of NH4+ sorption by biochar and our curated data set provides a potentially valuable scale against which future estimates can be assessed.

Comprehensive antibody profiling of mRNA vaccination in children.

While children have been largely spared from COVID-19 disease, the emergence of viral variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remains unclear. Given the recent announcement of incomplete immunity induced by the pediatric dose of the BNT162b2 vaccine in young children, here we aimed to deeply profile and compare the vaccine-induced humoral immune response in 6-11 year old children receiving the pediatric (50µg) or adult (100µg) dose of the mRNA-1273 vaccine compared to adults and naturally infected children or children that experienced multi inflammatory syndrome in children (MIS-C) for the first time. Children elicited an IgG dominant vaccine induced immune response, surpassing adults at a matched 100µg dose, but more variable immunity at a 50µg dose. Irrespective of titer, children generated antibodies with enhanced Fc-receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron receptor binding domain-binding, but robustly preserved omicron Spike-receptor binding, with robustly preserved Fc-receptor binding capabilities, in a dose dependent manner. These data indicate that while both 50µg and 100µg of mRNA vaccination in children elicits robust cross-VOC antibody responses, 100ug of mRNA in children results in highly preserved omicron-specific functional humoral immunity.

SARS-CoV-2 mRNA vaccination elicits robust antibody responses in children.

Although children have been largely spared from coronavirus disease 2019 (COVID-19), the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with increased transmissibility, combined with fluctuating mask mandates and school reopenings, has led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remain unclear. Here, we aimed to deeply profile the vaccine-induced humoral immune response in 6- to 11-year-old children receiving either a pediatric (50 µg) or adult (100 µg) dose of the mRNA-1273 vaccine and to compare these responses to vaccinated adults, infected children, and children who experienced multisystem inflammatory syndrome in children (MIS-C). Children elicited an IgG-dominant vaccine-induced immune response, surpassing adults at a matched 100-µg dose but more variable immunity at a 50-µg dose. Irrespective of titer, children generated antibodies with enhanced Fc receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron-specific receptor binding domain, but robustly preserved omicron spike protein binding. Fc receptor binding capabilities were also preserved in a dose-dependent manner. These data indicate that both the 50- and 100-µg doses of mRNA vaccination in children elicit robust cross-VOC antibody responses and that 100-µg doses in children result in highly preserved omicron-specific functional humoral immunity.

Virologic features of SARS-CoV-2 infection in children.

BACKGROUND: Data on pediatric COVID-19 has lagged behind adults throughout the pandemic. An understanding of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. METHODS: Respiratory swabs were collected from children with COVID-19. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences. RESULTS: 110 children with COVID-19 (median age 10 years, range 2 weeks-21 years) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first five days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified. CONCLUSIONS: Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.

Long-term effects of grain husk and paper fibre sludge biochar on acidic and calcareous sandy soils - A scale-up field experiment applying a complex monitoring toolkit.

Biochar is produced from a wide range of organic materials by pyrolysis, specifically for improvement of poor quality soils. One of the main issues nowadays in studying biochar as soil amendment is to upscale experiments and move from short-term, laboratory conditions to long-term field trials. This paper presents a long-term field study, being the final step of a scale-up technology development, on grain husk and paper fibre sludge biochar application for soil improvement with focus on two degraded soil types of a temperate region. The effects of biochar on an acidic and a calcareous sandy agricultural soil were studied applying a complex approach including physico-chemical, biological and ecotoxicological methods. Our study demonstrated that the applied biochar had positive direct and indirect influences on the acidic sandy soil, but these effects were different in terms of extent and time. 30 t/ha biochar addition improved the pH of the acidic sandy soil by 24% and also increased significantly the nutrient concentrations (P2O5 by 68%, K2O by 11% and organic matter by 33%), and the water-holding capacity after 30 months. Furthermore, biochar addition improved also the microbiological activity and diversity in the acidic sandy soil. Biochar application did not induce any negative effects. Biochar had no toxic effect on the plants and the biochar-treated soil provided a more liveable habitat for soil living animals than the untreated acidic sandy soil. The favourable biochar-mediated influences on soil properties were manifested mainly in the acidic sandy soil, proving that the biochar-related advantages have to be verified for different soil types. The benefits of grain husk and paper fibre sludge biochar application in an acidic sandy soil were confirmed on the long term by the applied tiered approach.

Acidic sandy soil improvement with biochar - A microcosm study.

Biochar produced from a wide range of organic materials by pyrolysis has been reported as a means to improve soil physical properties, fertility and crop productivity. However, there is a lack of studies on the complex effects of biochar both on the degraded sandy soil physico-chemical properties and the soil biota as well as on toxicity, particularly in combined application with fertilizer and compost. A 7-week microcosm experiment was conducted to improve the quality of an acidic sandy soil combining variations in biochar types and amounts, compost and fertilizer application rates. The applied biochars were produced from different feedstocks such as grain husks, paper fibre sludge and wood screenings. The main purpose of the microcosm experiment was to assess the efficiency and applicability of different biochars as soil amendment prior to field trials and to choose the most efficient biochar to improve the fertility, biological activity and physical properties of acidic sandy soils. We complemented the methodology with ecotoxicity assessment to evaluate the possible risks to the soil as habitat for microbes, plants and animals. There was clear evidence of biochar-soil interactions positively affecting both the physico-chemical properties of the tested acidic sandy soil and the soil biota. Our results suggest that the grain husk and the paper fibre sludge biochars applied to the tested soil at 1% and 0.5 w/w% rate mixed with compost, respectively can supply a more liveable habitat for plants and soil living animals than the acidic sandy soil without treatment.

Brain Iron and Zinc Contents of German Patients with Alzheimer Disease.

Our first project aimed to determine the average values of Fe and Zn in normal German human brain (5 individuals, 10 brain parts). Determinations were carried out by instrumental neutron activation analysis in Berlin. Quality control measurements were performed using National Institute of Standard Technology standard reference materials. The present results show non-homogeneous distribution of Fe and Zn in normal human brain. Our second goal was to study the possible elemental concentration changes in German patients with Alzheimer disease (5 subjects, 10 brain regions). Fe and Zn values are found to be significantly changed in some AD brain regions compared to the controls. Another object of this work was to extend the method for the determination of elemental concentration not only in whole brain samples (high fat content) but - applying two types of solvent extraction - in lipid fraction and in brain tissue without lipid.

Synovial fluid exoglycosidases are predictors of rheumatoid arthritis and are effective in cartilage glycosaminoglycan depletion.

OBJECTIVE: To analyze enzymes involved in joint damage by simultaneous investigation of glycosidases and matrix metalloproteinases (MMPs) in patients with various joint diseases. METHODS: Activities of glycosidases (beta-D-glucuronidase, beta-D-N-acetyl-glucosaminidase, beta-D-N-acetyl-galactosaminidase, beta-D-galactosidase, and alpha-D-mannosidase) were tested at an acidic pH as well as at the original pH of the synovial fluid (SF) samples in parallel with activities of MMP-1 and MMP-9. RESULTS: Patients with rheumatoid arthritis (RA) were characterized by significantly elevated activities of beta-D-glucuronidase and beta-D-N-acetyl-glucosaminidase in SF compared with patients with osteoarthritis, seronegative spondylarthritis, or acute sports injury. To select the best predictor for distinguishing among patient groups, a stepwise logistic regression analysis was performed; the strongest association was found to be between RA and beta-D-glucuronidase/beta-D-N-acetyl-glucosaminidase activities (measured at the pH of the SF). Further, a significant correlation was observed between the activity of SF beta-D-N-acetyl-glucosaminidase and the level of rheumatoid factor. In vitro digestion of human hyaline cartilage samples revealed that the dominant glycosidases, alone or in combination with MMPs, proved to be effective in depleting glycosaminoglycans (GAGs) from cartilage. CONCLUSION: These results suggest that exoglycosidases, which are present in the SF of RA patients, may contribute to the depletion of GAGs from cartilage and thereby facilitate the invasion of synovial cells and their attachment to cartilage in RA.