Bergmannlarkin7181
A sensitive electrochemical sensor for sunset yellow (SY) was constructed based on cetyltrimethylammonium bromide (CTAB) functionalized graphene (Gr) and Cu/Zr-MOF electrode modified materials. The CTAB-Gr-Cu/Zr-MOF composites were synthesized by using a mild method and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and EDX spectrum. The combination of Cu/Zr-MOF and graphene exhibited synergetic effect of the strong accumulation efficiency, fast electron transfer rate and more sensing sites towards the oxidation of SY. The new modified materials remarkably increased the electrochemical response of SY to 6.53-fold when comparing with bare electrode. Under the optimized conditions, the oxidation peak currents of SY had a linear relationship with its concentration in a wide range from 0.10 to 8.00 μM and 40.00-1000.00 μM, and the limit of detection was 6.68 nM (S/N = 3). The electrochemical method shows high sensitivity, stability, reproducibility and is successfully applied in the determination of SY in soft drinks.Acrylamide and furan are environmental and food contaminants that are metabolized by cytochrome P450 2E1 (CYP2E1), giving rise to glycidamide and cis-2-butene-1,4-dial (BDA) metabolites, respectively. Both glycidamide and BDA are electrophilic species that react with nucleophilic groups, being able to introduce mutations in DNA and perform epigenetic remodeling. However, whereas these carcinogens are primarily metabolized in the liver, the carcinogenic potential of acrylamide and furan in this organ is still controversial, based on findings from experimental animal studies. With the ultimate goal of providing further insights into this issue, we explored in vitro, using a hepatocyte cell line and a hepatocellular carcinoma cell line, the putative effect of these metabolites as carcinogens and cancer promoters. Molecular alterations were investigated in cells that survive glycidamide and BDA toxicity. We observed that those cells express CD133 stemness marker, present a high proliferative capacity and display an adjusted expression profile of genes encoding enzymes involved in oxidative stress control, such as GCL-C, GSTP1, GSTA3 and CAT. These molecular changes seem to be underlined, at least in part, by epigenetic remodeling involving histone deacetylases (HDACs). Although more studies are needed, here we present more insights towards the carcinogenic capacity of glycidamide and BDA and also point out their effect in favoring hepatocellular carcinoma progression.
Ischemia-reperfusion injury (IRI) is an important pathophysiological condition that can cause cell injury and large-scale tissue injury in the nervous system. Previous studies have shown that epigenetic regulation may play a role in the pathogenesis of IRI.
In this study, we isolated mouse cortical neurons and constructed an oxygen-glucose deprivation/reoxygenation (OGD) model to explore the change in DNA methylation and its effect on the expression of corresponding genes.
We found that DNA methylation in neurons increased with hypoxia duration and that hypermethylation of numerous promoters and 3'-untranslated regions increased. We performed Gene Ontology enrichment analysis to study gene function and Kyoto Encyclopedia of Genes and Genomes pathway analysis to identify the pathways associated with gene regulation. The results showed that hypermethylation-related genes expressed after OGD were related to physiological pathways such as neuronal projection, ion transport, growth and development, while hypes pathway analysis to identify the pathways associated with gene regulation. The results showed that hypermethylation-related genes expressed after OGD were related to physiological pathways such as neuronal projection, ion transport, growth and development, while hypomethylation-related genes were related to pathological pathways such as the external apoptosis signaling pathway, neuronal death regulation, and regulation of oxidative stress. However, the changes in DNA methylation were specific for certain genes and may have been related to OGD-induced neuronal damage. Importantly, we integrated transcription and DNA methylation data to identify several candidate target genes, including hypomethylated Apoe, Pax6, Bmp4, and Ptch1 and hypermethylated Adora2a, Crhr1, Stxbp1, and Tac1. This study further indicated the effect of DNA methylation on gene function in brain IRI from the perspective of epigenetics, and the identified genes may become new targets for achieving neuroprotection in the brain after IRI.
This study aims to establish an optimization procedure to define the cut-offs of quantitative assays for acetylcholine receptor antibody (AChRAb), evaluate their diagnostic performance in myasthenia gravis (MG), and explore the association with clinical features.
Samples from a representative cohort of 77 MG patients, 80 healthy controls (HC) and 80 other autoimmune diseases (OAD) patients were tested using competitive inhibition ELISA and RIA. Raw values (OD and cpm) and processed values (inhibition rate, binding rate and concentration) were used to define the cut-offs with statistical methods, a rough method, and receiver operating characteristic (ROC) curve. Optimal cut-offs were selected by comparing false positive rates in HC and OAD individuals. The diagnostic performance was evaluated in whole MG cohort and subgroups. Agreement between ELISA and RIA for AChRAb positivity were examined with Kappa test and McNemar test. Clinical association with AChRAb was explored by comparison among subgroups and wal quantitative measures of AChRAb levels. There are good agreements on diagnostic performance between two assays. Quantitative values are more informative than positivity in association with clinical features.
The emergence of increasingly antimicrobial-resistant Salmonella enterica serovar Typhi (S Typhi) threatens to undermine effective treatment and control. Understanding where antimicrobial resistance in S Typhi is emerging and spreading is crucial towards formulating effective control strategies.
In this genomic epidemiology study, we sequenced the genomes of 3489 S Typhi strains isolated from prospective enteric fever surveillance studies in Nepal, Bangladesh, Pakistan, and India (between 2014 and 2019), and combined these with a global collection of 4169 S Typhi genome sequences isolated between 1905 and 2018 to investigate the temporal and geographical patterns of emergence and spread of antimicrobial-resistant S Typhi. We performed non-parametric phylodynamic analyses to characterise changes in the effective population size of fluoroquinolone-resistant, extensively drug-resistant (XDR), and azithromycin-resistant S Typhi over time. We inferred timed phylogenies for the major S Typhi sublineages and usecement of drug-susceptible clades.
Independent acquisition of plasmids and homoplastic mutations conferring antimicrobial resistance have occurred repeatedly in multiple lineages of S Typhi, predominantly arising in south Asia before spreading to other regions.
Bill & Melinda Gates Foundation.
Bill & Melinda Gates Foundation.
The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae (Salmonella enterica serovars Typhi and Paratyphi), is largely unknown in regions without blood culture surveillance. The aim of this study was to evaluate whether new diagnostic serological markers for typhoidal Salmonella can reliably estimate population-level incidence.
We collected longitudinal blood samples from patients with blood culture-confirmed enteric fever enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana between 2016 and 2021 and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to hemolysin E and S Typhi lipopolysaccharide. We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titres and decay rate to estimate population-level incidence rates from cross-sectional serosurveys.
The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children younger than 5 years ranged between 58·5 per 100 person-years (95% CI 42·1-81·4) in Dhaka, Bangladesh, to 6·6 per 100 person-years (4·3-9·9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates.
The approach described here has the potential to expand the geographical scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographical regions and time.
Bill & Melinda Gates Foundation.
For the Nepali, Bengali and Urdu translations of the abstract see Supplementary Materials section.
For the Nepali, Bengali and Urdu translations of the abstract see Supplementary Materials section.
Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines.
In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or anIn-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit.
National Institute for Communicable Diseases, a Division of the National Health Laboratory Service.
For the Zulu translation of the abstract see Supplementary Materials section.
For the Zulu translation of the abstract see Supplementary Materials section.Adolescents are a crucial generation, with the potential to bring future social and economic success for themselves and their countries. More than 90% of adolescents living with HIV reside in sub-Saharan Africa, where their mental health is set against a background of poverty, familial stress, service gaps, and an HIV epidemic that is now intertwined with the COVID-19 pandemic. In this Series paper, we review systematic reviews, randomised trials, and cohort studies of adolescents living with and affected by HIV. We provide a detailed overview of mental health provision and collate evidence for future approaches. We find that the mental health burden for adolescents living with HIV is high, contributing to low quality of life and challenges with adherence to antiretroviral therapy. Mental health provision is scarce, infrastructure and skilled providers are missing, and leadership is needed. Evidence of effective interventions is emerging, including specific provisions for mental health (eg, cognitive behavioural therapy, problem-solving, mindfulness, and parenting programmes) and broader provisions to prevent drivers of poor mental health (eg, social protection and violence prevention).
