Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. CONCLUSION: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.

Insight into recent advances in microalgae biogranulation in wastewater treatment.

Microalgae-based technology is widely utilized in wastewater treatment and resource recovery. However, the practical implementation of microalgae-based technology is hampered by the difficulty in separating microalgae from treated water due to the low density of microalgae. This review is designed to find the current status of the development and utilization of microalgae biogranulation technology for better and more cost-effective wastewater treatment. This review reveals that the current trend of research is geared toward developing microalgae-bacterial granules. Most previous works were focused on studying the effect of operating conditions to improve the efficiency of wastewater treatment using microalgae-bacterial granules. Limited studies have been directed toward optimizing operating conditions to induce the secretion of extracellular polymeric substances (EPSs), which promotes the development of denser microalgae granules with enhanced settling ability. Likewise, studies on the understanding of the EPS role and the interaction between microalgae cells in forming granules are scarce. Furthermore, the majority of current research has been on the cultivation of microalgae-bacteria granules, which limits their application only in wastewater treatment. Cultivation of microalgae granules without bacteria has greater potential because it does not require additional purification and can be used for border applications.

The most recent development in microalgae biogranulation research is highlighted.Factors affecting microalgae granule development are discussed for the first time.Duration to develop granules is a crucial aspect that needs further research.Cultivation of single-species microalgae for rapid harvesting needs more attention.

Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia.

Biomarkers in chronic lymphocytic leukemia (CLL) allow assessment of prognosis. However, the validity of current prognostic biomarkers based on a single assessment point remains unclear for patients who have survived one or more years. Conditional survival (CS) studies that address how prognosis may change over time, especially in prognostic subgroups, are still rare. We performed CS analyses to estimate 5-year survival in 1-year increments, stratified by baseline disease characteristics and known risk factors in two community-based cohorts of CLL patients (Freiburg University Hospital (n = 316) and Augsburg University Hospital (n = 564)) diagnosed between 1984 and 2021. We demonstrate that 5-year CS probability is stable (app. 75%) for the entire CLL patient cohort over 10 years. While age, sex, and stage have no significant impact on CS, patients with high-risk disease features such as non-mutated IGHV, deletion 17p, and high-risk CLL-IPI have a significantly worse prognosis at diagnosis, and 5-year CS steadily decreases with each additional year survived. Our results confirm that CLL patients have a stable survival probability with excess mortality and that the prognosis of high-risk CLL patients declines over time. We infer that CS-based prognostic information is relevant for disease management and counseling of CLL patients.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Essentialism and the criminal legal system.

OBJECTIVE: Existing literature has yet to conceptualize and consolidate research on psychological essentialism and its relation to the criminal legal system, particularly in terms of explaining how individuals with justice involvement have been and could be differentially impacted across contexts. This article explores essentialism in the criminal legal system, including its potential consequences for inequity. METHOD: We review research on essentialism as a psychological construct, its common applications to different social categorizations, and its trickle-down effects within the criminal legal system. RESULTS: Empirical work suggests that biases stemming from essentialism have the potential to severely affect individuals within the criminal legal system. Beyond assigning immutable properties across social groups, essentialism can give rise to biased attributions of responsibility and blame and affect decisions and behavior within three core domains of the criminal legal system: jury decision making, sentencing decisions, and public support for punitive policies. CONCLUSIONS: We propose future policy recommendations to mitigate the adverse effects of essentialism in the criminal legal system, focusing especially on how using and adopting person-first language (focusing on people before characteristics) across society and policy can help to combat bias across criminal legal domains. Future research is needed on how to best address the adverse effects of essentialism and its biasing effects in the criminal legal system, as well as to examine the effects of essentialism in different legal contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genomic Sequencing Surveillance to Identify Respiratory Syncytial Virus Mutations, Arizona, USA.

We conducted surveillance of respiratory syncytial virus (RSV) genomic sequences for 100 RSV-A and 27 RSV-B specimens collected during November 2022-April 2023 in Arizona, USA. We identified mutations within prefusion F-protein antigenic sites in both subtypes. Continued genomic surveillance will be critical to ensure RSV vaccine effectiveness.

Spontaneous Closure of Full-Thickness Macular Holes.

PURPOSE: To describe retinal morphology and vision recovery after spontaneous closure of full-thickness macular hole (FTMH). MATERIALS AND METHODS: Retrospective, observational study. From a database containing 750 FTMH, we included 23 cases. All patients had a complete ophthalmic examination. Swept-source optical coherence tomography angiography was performed. RESULTS: Prior to spontaneous closure in 11 women and 12 men (mean age 67 years), the mean minimum FTMH diameter was 201 µm, and mean base FTMH diameter was 638 µm. Visual acuity improved from 0.29 Snellen to 0.47 Snellen (p = 0.001) after 6 months and showed no further improvement. Spontaneous closure of FTMH was associated with vitreous detachment in less than half of the cases. Irregularities in the deep vascular layer and hyporeflective areas in the choriocapillaris were noted. DISCUSSION: Equal sex distribution of spontaneous closures (1:1) differs from the high prevalence of females seen in the literature. Complete visual recovery is uncommon in cases of spontaneous closure of FTMH. It might be explained by prolonged defects of the choriocapillaris layer. These findings, along with the evolution of the various morphologies reported in the study, could possibly suggest that delaying vitrectomy while hoping for spontaneous closure might not be justified.

Genomic Sequencing of SARS-CoV-2 E484K Variant B.1.243.1, Arizona, USA.

Genomic surveillance can provide early insights into new circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. While conducting genomic surveillance (1,663 cases) from December 2020-April 2021 in Arizona, USA, we detected an emergent E484K-harboring variant, B.1.243.1. This finding demonstrates the importance of real-time SARS-CoV-2 surveillance to better inform public health responses.

Citrin deficiency ­ pathogenesis, clinical and biochemical manifestation, diagnostics, treatment / Deficyt cytrynu.

Citrin deficiency is an inherited metabolic disease caused by biallelic pathogenic variants in the SLC25A13 gene encoding the carrier protein called citrin. There are observed three characteristic clinical and biochemical age-dependent phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency, failure to thrive and dyslipidemia caused by citrin deficiency and adult-onset citrullinemia type 2. The paper presents the characteristics of the pathogenesis of citrin deficiency, clinical and biochemical delineation of individual phenotypes, differential diagnosis and treatment of citrin deficiency.

The P300 auditory event-related potential as a method to assess the benefit of contralateral hearing aid use in bimodal listeners: a proof-of-concept.

Objective: Bimodal listeners vary in the amount of benefit they receive from wearing the contralateral hearing aid. This may partially depend on the listener's auditory processing capacities. The current study explores whether the P300 event-related potential can provide insight into the mechanisms underlying the benefits of wearing a contralateral hearing aid.Design: P300s were recorded using an oddball paradigm with 500 and 250 Hz tone-bursts as standard and deviant stimuli, respectively. Subjects counted the number of deviants - a measure of performance. N2b latencies, P300 latencies, N2b-P300 amplitudes, and performance were assessed during CI-only and bimodal listening.Study sample: Five bimodal listeners.Results: P300s were present in four subjects. Amplitudes were larger during bimodal listening (bimodal: 22.3 ± 4.83 µV, CI-only: 13.1 ± 3.86 µV). Both N2b and P300 latencies were shorter during bimodal (N2b: 265 ± 20.0 ms, P300: 551 ± 129.4 ms) than CI-only listening (N2b: 326 ± 42.2 ms, P300: 402 ± 38.4 ms). While performance often reached ceiling level, the difference between the standard and deviant was generally more salient during bimodal listening.Conclusions: This study provides a proof-of-concept, suggesting that P300s may provide insight into benefits that are not always measurable with behavioural tasks.

Mania and psychosis associated with right parietal meningioma.

Objective: Meningioma is the most common type of primary central nervous system and intracranial tumor, and psychiatric changes attributed to meningioma include depression, apathy, psychosis, and personality changes. We present a case of a 59-year-old man with right parietal meningioma who developed mania with psychotic features throughout multiple hospitalizations. Method: Single-case report. Results: The patient originally presented with headache and bilateral lower extremity weakness. He was found to have a large medial sphenoidal wing meningioma and a small right parietal meningioma. The sphenoidal wing meningioma was removed via craniotomy, but the right parietal meningioma was not resected. In the following years, the patient developed symptoms of mania and psychosis which coincided with an increase in size of the right parietal meningioma. Conclusions: Previous studies have linked right parietal meningioma to psychosis, but this case is one of the first to suggest that right parietal meningioma may be associated with the development of mania along with psychotic features.

A review on influencing factors on the minimum inhibitory concentration of essential oils.

With growing interest in essential oils as natural preservatives in the food industry, the literature is expanding enormously. To understand the antimicrobial activity of essential oils, the antimicrobial mechanism of individual essential oil (EO) compounds, and their minimum inhibitory concentrations (MICs), are interesting starting points for research. Therefore, and to get insight into the factors influencing their antimicrobial activities, the Web of Science was searched for MICs of EO compounds (1995-2016). Many MICs for individual EO compounds have already been reported in the literature, but there is large variability in these data, even for the MIC of the same compound against the same species. No correlation was found between the tested structural parameters of EO compounds (polarity, water solubility, dissociation constant, molecular weight and molecular complexity) and their MICs against all microorganisms, Gram-negative bacteria, Gram-positive bacteria and fungi. Few clear differences in sensitivity between microorganisms could be found. Based on this review it is clear that different incubation conditions, culture media and the use of emulsifiers/solvents have an influence on the MIC, causing big variance. This review points out the need for a good international standard method to assess the antimicrobial activity of EO compounds for better comparability between studies.

Nitrite pre-treatment of dewatered sludge for microbial fuel cell application.

The effect of pre-treatment of dewatered sludge using different nitrite concentrations and pH for microbial fuel cell (MFC) application was investigated. The results show that the addition of nitrite was feasible to increase the solubilization rate of the sludge and may reduce mass transfer limitation at the anode. This helped the MFC to reach higher voltage and to generate more power. The higher free nitrous acid (FNA) concentration under the acidic condition helped to increase sludge solubilization. However, under an alkaline condition, during which the FNA concentration was relatively low, the solubilization of the sludge was higher. The highest voltage and power density produced was 390 mV and 153 mW/m2, respectively, with the addition of nitrite at 100 mg-N/L and pH 9. Furthermore, it was found that elevated levels of FNA could inhibit electrogenic bacteria thus reducing power generation.

Gene mutations and clonal architecture in myelodysplastic syndromes and changes upon progression to acute myeloid leukaemia and under treatment.

Knowledge of the molecular and clonal characteristics in the myelodysplastic syndromes (MDS) and during progression to acute myeloid leukaemia (AML) is essential to understand the disease dynamics and optimize treatment. Sequencing serial bone marrow samples of eight patients, we observed that MDS featured a median of 3 mutations. Mutations in genes involved in RNA-splicing or epigenetic regulation were most frequent, and exclusively present in the major clone. Minor subclones were distinguishable in three patients. As the MDS progressed, a median of one mutation was gained, leading to clonal outgrowth. No AML developed genetically independent of a pre-existing clone. The gained mutation mostly affected genes encoding signalling proteins. Additional acquisition of genomic aberrations frequently occurred. Upon treatment, emergence of new clones could be observed. As confirmed by single-cell sequencing, multiple mutations in identical genes in different clones were present within individual patients. DNA-methylation profiling in patients without identification of novel mutations in AML revealed methylation changes in individual genes. In conclusion, our data complement previous observations on the mutational and clonal characteristics in MDS and at progression. Moreover, DNA-methylation changes may be associated with progression in single patients. Redundancy of mutated genes in different clones suggests fertile grounds promoting clonal selection or acquisition.

Normal Reference Ranges for Pulmonary Artery Diameters in Preterm Infants.

To establish normal reference ranges and Z-scores for pulmonary artery diameters in preterm infants and their correlation with body surface area, body weight, and chronological age. In a prospective study, 268 preterm infants, who fulfilled the inclusion criteria were examined. Echocardiograms were performed to measure the main pulmonary artery, right pulmonary artery, and left pulmonary artery diameters on day(s) 0 to -6 of life and at weekly intervals until they reached 36 weeks of age. Body surface area was divided into thirteen groups from 0.07 to 0.19 m2. The mean gestational age was 29.8 (±2.38 SD) weeks, ranging between 24 and 35, the mean body weight was 1479 (±413 SD) grams, ranging between 588 and 3380, and the mean body surface area was 0.13 m2, ranging between 0.07 and 0.19 m2. All the pulmonary artery diameters correlated well with both body weight and body surface area. Reference ranges, with mean ± SD, range, and Z-scores for aortic diameters according to body surface area were calculated. A significant gradual increase was observed in main and branch pulmonary artery diameters with increasing body surface area. Overall, a progressive and significant increase for main and branch pulmonary artery diameters was observed during the first nine weeks of life. The main and branch pulmonary artery diameters were found to have significant correlation with body surface area. The study also provides reference data with Z-scores, which can be used as a normal reference tool for measuring the main pulmonary artery, right, and left pulmonary artery diameters of preterm infants against body surface area.

Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes.

Oxidative stress mediated clustering of membrane protein band 3 plays an essential role in the clearance of damaged and aged red blood cells (RBCs) from the circulation. While a number of previous experimental studies have observed changes in band 3 distribution after oxidative treatment, the details of how these clusters are formed and how their properties change under different conditions have remained poorly understood. To address these issues, a framework that enables the simultaneous monitoring of the temporal and spatial changes following oxidation is needed. In this study, we established a novel simulation strategy that incorporates deterministic and stochastic reactions with particle reaction-diffusion processes, to model band 3 cluster formation at single molecule resolution. By integrating a kinetic model of RBC antioxidant metabolism with a model of band 3 diffusion, we developed a model that reproduces the time-dependent changes of glutathione and clustered band 3 levels, as well as band 3 distribution during oxidative treatment, observed in prior studies. We predicted that cluster formation is largely dependent on fast reverse reaction rates, strong affinity between clustering molecules, and irreversible hemichrome binding. We further predicted that under repeated oxidative perturbations, clusters tended to progressively grow and shift towards an irreversible state. Application of our model to simulate oxidation in RBCs with cytoskeletal deficiency also suggested that oxidation leads to more enhanced clustering compared to healthy RBCs. Taken together, our model enables the prediction of band 3 spatio-temporal profiles under various situations, thus providing valuable insights to potentially aid understanding mechanisms for removing senescent and premature RBCs.

Automated non-EEG based seizure detection: Do users have a say?

PURPOSE: Quality of life of patients with epilepsy depends largely upon unpredictability of seizure occurrence and would improve by predicting seizures or at least by detecting seizures (after their clinical onset) and react timely. Detection systems are available and researched, but little is known about the actual need and user preferences. The first indicates the market potential; the second allows us to incorporate user requirements into the engineering process. METHODS: We questioned 20 pediatric and young adult patients, 114 caregivers, and 21 involved medical doctors and described, analyzed, and compared their experiences with systems for seizure detection, their opinions on usefulness and purpose of seizure detection, and their requirements for such a device. RESULTS: Experience with detection systems is limited, but 65% of patients and caregivers and 85% of medical doctors express the usefulness, more so during night than day. The need is higher in patients with more severe intellectual disability. The higher the seizure frequency, the higher the need, opinions in the seizure-free group being more divided. Most patients and caregivers require 100% correct detection, and on average, one false alarm per seizure (one per week for those seizure-free) is accepted. Medical doctors allow 90% correct detections and between two false alarms per week and one per month depending on seizure frequency. Detection of seizures involving heavy movement and falls is judged most important by patients and caregivers and second to most by medical doctors. The latter judge heart rate monitoring most relevant, both towards seizure detection and SUDEP (sudden unexpected death in epilepsy) prevention. CONCLUSIONS: The results, including a goal of 90% correct detections and one false alarm per seizure, should be considered in development of seizure detectors.

Age-Related Changes in Binaural Interaction at Brainstem Level.

OBJECTIVES: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. DESIGN: Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. RESULTS: Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. CONCLUSIONS: Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.