Multiphase Ozonolysis of Bisphenol A: Chemical Transformations on Surfaces in the Environment.

High global plastic production volumes have led to the widespread presence of bisphenol compounds in human living and working environments. The most common bisphenol, bisphenol A (BPA), despite being endocrine disruptive and estrogenic, is still not fully banned worldwide, leading to continued human exposure via particles in air, dust, and surfaces in both outdoor and indoor environments. While its abundance is well documented, few studies have addressed the chemical transformations of BPA, the properties of its reactive products, and their toxicity. Here, the first gas-surface multiphase ozonolysis experiment of BPA thin films, at a constant ozone mixing ratio of 100 ppb, was performed in a flow tube for periods up to 24 h. Three transformation products involving the addition of 1, 2, and 3 oxygen atoms to the molecule were identified by LC-ESI-HRMS analyses. Exposure of indoor air to thin BPA surface films and BPA-containing thermal paper over periods of days validated the flow tube experiments, demonstrating the rapid nature of this multiphase ozonolysis reaction at atmospherically relevant ozone levels. Multiple transformation pathways are proposed that are likely applicable to not only BPA but also emerging commercial bisphenol products.

Characterization and predictive risk scoring of long COVID in a south indian cohort after breakthrough COVID infection; a prospective single centre study.

BACKGROUND: With the World Health Organization (WHO) declaring an end to the COVID-19 pandemic, the focus has shifted to understanding and managing long-term post-infectious complications. "Long COVID," characterized by persistent or new onset symptoms extending beyond the initial phase of infection, is one such complication. This study aims to describe the incidence, clinical features and risk profile of long COVID among individuals in a South Indian cohort who experienced post-ChAdOx1 n-Cov-2 vaccine breakthrough infections. METHODS: A single-centre hospital-based prospective observational study was conducted from October to December 2021. The study population comprised adult patients (> 18 years) with a confirmed COVID-19 diagnosis who had received at least a single dose of vaccination. Data was collected using a specially tailored questionnaire at week 2, week 6, and week 12 post-negative COVID-19 test. A propensity score based predictive scoring system was developed to assess the risk of long COVID. RESULTS: Among the 414 patients followed up in the study, 164 (39.6%) reported long COVID symptoms persisting beyond 6 week's post-infection. The presence of long COVID was significantly higher among patients above 65 years of age, and those with comorbidities such as Type II Diabetes Mellitus, hypertension, dyslipidemia, coronary artery disease, asthma, and cancer. Using backwards selection, a reduced model was developed, identifying age (OR 1.053, 95% CI 0.097-1.07, p < 0.001), hypertension (OR 2.59, 95% CI 1.46-4.59, p = 0.001), and bronchial asthma (OR 3.7176, 95% CI 1.24-11.12, p = 0.018) as significant predictors of long COVID incidence. A significant positive correlation was observed between the symptomatic burden and the number of individual comorbidities. CONCLUSIONS: The significant presence of long COVID at 12 weeks among non-hospitalised patients underscores the importance of post-recovery follow-up to assess for the presence of long COVID. The predictive risk score proposed in this study may help identify individuals at risk of developing long COVID. Further research is needed to understand the impact of long COVID on patients' quality of life and the potential role of tailored rehabilitation programs in improving patient outcomes.

Complete genome sequence of Methanothermobacter sp. DP, a hydrogenotrophic and thermophilic methanogen.

Here, we report the complete genome sequence of the thermophilic hydrogenotrophic methanogen Methanothermobacter sp. DP isolated in South Korea from an anaerobic digester fed with cigarette waste. The genome consists of 1,693,285 bp, with 1,772 protein-coding genes and a GC content of 48.8%.

Temperature Profile Measurement From Radiofrequency Nasal Airway Reshaping Device.

OBJECTIVE: Nasal airway obstruction (NAO) is caused by various disorders including nasal valve collapse (NVC). A bipolar radiofrequency (RF) device (VivAer®, Aerin Medical, Sunnyvale, CA) has been used to treat NAO through RF heat generation to the upper lateral cartilage (ULC). The purpose of this study is to measure temperature elevations in nasal tissue, using infrared (IR) radiometry to map the spatial and temporal evolution of temperature. STUDY DESIGN: Experimental and computational. METHODS: Composite porcine nasal septum was harvested and sectioned (1 mm and 2 mm). The device was used to heat the cartilage in composite porcine septum. An IR camera (FLIR® ExaminIR, Teledyne, Wilsonville, OR) was used to image temperature on the back surface of the specimen. These data were incorporated into a heat transfer finite element model that also calculated tissue damage using Arrhenius rate process. RESULTS: IR temperature imaging showed peak back surface temperatures of 49.57°C and 42.21°C in 1 and 2 mm thick septums respectively. Temperature maps were generated demonstrating the temporal and spatial evolution of temperature. A finite element model generated temperature profiles with respect to time and depth. Rate process models using Arrhenius coefficients showed 30% chondrocyte death at 1 mm depth after 18 s of RF treatment. CONCLUSION: The use of this device creates a thermal profile that may result in thermal injury to cartilage. Computational modeling suggests chondrocyte death extending as deep as 1.4 mm below the treatment surface. Further studies should be performed to improve dosimetry and optimize the heating process to reduce potential injury. Laryngoscope, 134:1063-1070, 2024.

Poly-gamma-glutamic acid biopolymer: a sleeping giant with diverse applications and unique opportunities for commercialization.

Poly-gamma-glutamic acid (γ-PGA) is a biodegradable, non-toxic, ecofriendly, and non-immunogenic biopolymer. Its phenomenal properties have gained immense attention in the field of regenerative medicine, the food industry, wastewater treatment, and even in 3D printing bio-ink. The γ-PGA has the potential to replace synthetic non-degradable counterparts, but the main obstacle is the high production cost and lower productivity. Extensive research has been carried out to reduce the production cost by using different waste; however, it is unable to match the commercialization needs. This review focuses on the biosynthetic mechanism of γ-PGA, its production using the synthetic medium as well as different wastes by L-glutamic acid-dependent and independent microbial strains. Furthermore, various metabolic engineering strategies and the recovery processes for γ-PGA and their possible applications are discussed. Finally, highlights on the challenges and unique approaches to reduce the production cost and to increase the productivity for commercialization of γ-PGA are also summarized.

Recent Advances in Bioactive Peptides as Functional Food for Health Promotions and Medicinal Applications.

Bioactive peptides obtained from natural resources are useful due to their ability to prevent the risk of dreadful conditions such as hypertension, cancers, obesity and cardiovascular diseases. Proteins from food, plants, animals and dairy products are chemically or enzymatically hydrolyzed or fermented in the presence of microbes to produce bioactive peptides. Bioactive peptides are antioxidant, antihypertensive, anti-inflammatory, antiproliferative, antibacterial, anticancer, antimicrobial and some of them also show multiple bioactivities. Also, bioactive peptides offer much potential as nutraceuticals or functional food components. This paper reviews recent progress (2020-2022) on bioactive peptides derived from food, animals, plants, and dairy products. Emphasis is given to their production, purification, and potential use for health promotions and medicinal applications.

Cerebrospinal fluid indices as predictors of treatment response in autoimmune encephalitis.

BACKGROUND: Cerebrospinal fluid (CSF) indices reflecting intrathecal antibody production and blood-brain barrier impairment are not routinely assessed in patients with autoimmune encephalitis (AE). We aimed to study CSF indices and their association with the prognosis of AE. METHODS: This retrospective cohort study conducted at Amrita Institute of Medical Sciences (AIMS), Kochi, India, included 60 patients aged more than 18 years with definite/probable/possible AE admitted to the Department of Neurology from August 2016 to November 2021. We introduced a classification of treatment response based on modified Rankin Scale change over time and treatment modalities. RESULTS: In our cohort of 60 patients (six [10%] seropositive cases), a good rapid treatment response was associated with CSF white blood cell count of more than 4 cells/mm3 (OR, 4.57; 95% CI 1.31-15.96; P = .02) and positive immunoglobulin G (IgG) Local Synthesis (OR, 7.27; 95% CI 1.56-33.86; P = .01). Albumin Index had association with a poor Glasgow Coma Scale score at the nadir of the disease (OR, 1.17; 95% CI 1.01-1.34; P = .04). Similar results were yielded in the seronegative cohort. IgG Local Synthesis appeared to be a strong predictor for good rapid treatment response in both univariate and multivariate (adjusted OR, 28.71; 95% CI 2.12-389.22; P= .01) analysis. Time to immunotherapy was reversely correlated with good response overall (in the cohort with outliers removed [N = 49]: unadjusted OR 0.97, 95% CI 0.95-0.99; P= .01; adjusted OR 0.97; 95% CI 0.95-0.99; P= .008). CONCLUSION: CSF indices reflecting intrathecal antibody production and blood-brain barrier impairment appear to be promising predictors of disease severity and therapeutic response in patients with autoimmune encephalitis.

Widespread formation of toxic nitrated bisphenols indoors by heterogeneous reactions with HONO.

With numerous structurally diverse indoor contaminants, indoor transformation chemistry has been largely unexplored. Here, by integrating protein affinity purification and nontargeted mass spectrometry analysis (PUCA), we identified a substantial class of previously unrecognized indoor transformation products formed through gas-surface reactions with nitrous acid (HONO). Through the PUCA, we identified a noncommercial compound, nitrated bisphenol A (BPA), from house dust extracts strongly binding to estrogen-related receptor γ. The compound was detected in 28 of 31 house dust samples with comparable concentrations (ND to 0.30 µg/g) to BPA. Via exposing gaseous HONO to surface-bound BPA, we demonstrated it likely forms via a heterogeneous indoor chemical transformation that is highly selective toward bisphenols with electron-rich aromatic rings. We used 15N-nitrite for in situ labeling and found 110 nitration products formed from indoor contaminants with distinct aromatic moieties. This study demonstrates a previously unidentified class of chemical reactions involving indoor HONO, which should be incorporated into the risk evaluation of indoor contaminants, particularly bisphenols.

Neutrophilic Asthma and Potentially Related Target Therapies.

BACKGROUND: Neutrophilic asthma is generally associated with the absence of eosinophils and activation of non- predominant type 2 immunological pathways. It involves bronchial inflammation followed by different degrees of airway remodeling. Neutrophilic inflammation activates specific cellular and molecular pathways due to inhalation of environmental trigger factors such as exhaust fumes, cigarette smoke, occupation-related agents, and infections. OBJECTIVE: This review discusses the involvement of neutrophils in asthma and potentially related target therapies. RESULTS: Corticosteroid resistance is the hallmark of neutrophilic asthma which increases disease severity and leads to difficult-to-control asthma. Patients with neutrophil-dominant asthma are characterized by low levels of (or absence of) Th2 cytokines. Due to the shortage of effective treatments for neutrophilic asthma newer biologics are being developed that target type 2 asthma symptoms and phenotypes. Understanding different biomarkers, inflammatory pathways and treatment strategies involved in neutrophilic asthma will help to decrease adverse effects related to corticosteroid insensitivity. Better insight of targets involved in neutrophilic inflammation can lead to improved therapies. CONCLUSION: Further evaluation and clinical trials of emerging biologics involved in neutrophilic asthma needs to be performed before bringing them into clinical practice.

Cytogenetic, Genomic, and Functional Characterization of Pituitary Gonadotrope Cell Lines.

LßT2 and αT3-1 are important, widely studied cell line models for the pituitary gonadotropes that were generated by targeted tumorigenesis in transgenic mice. LßT2 cells are more mature gonadotrope precursors than αT3-1 cells. Microsatellite authentication patterns, chromosomal characteristics, and their intercellular variation have not been reported. We performed microsatellite and cytogenetic analysis of both cell types at early passage numbers. Short tandem repeat (STR) profiling was consistent with a mixed C57BL/6J × BALB/cJ genetic background, with distinct patterns for each cell type. Spectral karyotyping in αT3-1 cells revealed cell-to-cell variation in chromosome composition and pseudodiploidy. In LßT2 cells, chromosome counting and karyotyping demonstrated pseudotriploidy and high chromosomal variation among cells. Chromosome copy number variation was confirmed by single-cell DNA sequencing. Chromosomal compositions were consistent with a male sex for αT3-1 and a female sex for LßT2 cells. Among LßT2 stocks used in multiple laboratories, we detected two genetically similar but distinguishable lines via STR authentication, LßT2a and LßT2b. The two lines differed in morphological appearance, with LßT2a having significantly smaller cell and nucleus areas. Analysis of immediate early gene and gonadotropin subunit gene expression revealed variations in basal expression and responses to continuous and pulsatile GnRH stimulation. LßT2a showed higher basal levels of Egr1, Fos, and Lhb but lower Fos induction. Fshb induction reached significance only in LßT2b cells. Our study highlights the heterogeneity in gonadotrope cell line genomes and provides reference STR authentication patterns that can be monitored to improve experimental reproducibility and facilitate comparisons of results within and across laboratories.