Exploring the therapeutic targets of stevioside in management of type 2 diabetes by network pharmacology and in-silico approach.

AIMS: The main objective of the current study is to investigate the pathways and therapeutic targets linked to stevioside in the management of T2D using computational approaches. METHODS: We collected RNA-seq datasets from NCBI, then employed GREIN to retrieve differentially expressed genes (DEGs). Computer-assisted techniques DAVID, STRING and NetworkAnalyst were used to explore common significant pathways and therapeutic targets associated with T2D and stevioside. Molecular docking and dynamics simulations were conducted to validate the interaction between stevioside and therapeutic targets. RESULTS: Gene ontology and KEGG analysis revealed that prostaglandin synthesis, IL-17 signaling, inflammatory response, and interleukin signaling were potential pathways targeted by stevioside in T2D. Protein-protein interactions (PPI) analysis identified six common hub proteins (PPARG, PTGS2, CXCL8, CCL2, PTPRC, and EDN1). Molecular docking results showed best binding of stevioside to PPARG (-8 kcal/mol) and PTGS2 (-10.1 kcal/mol). Finally, 100 ns molecular dynamics demonstrated that the binding stability between stevioside and target protein (PPARG and PTGS2) falls within the acceptable range. CONCLUSIONS: This study reveals that stevioside exhibits significant potential in controlling T2D by targeting key pathways and stably binding to PPARG and PTGS2. Further research is necessary to confirm and expand upon these significant computational results.

NCCN Guidelines® Insights: Colorectal Cancer Screening, Version 1.2024.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.

Processing complementary foods to reduce mycotoxins in a medium scale Tanzanian mill: A hazard analysis critical control point (HACCP) approach.

Designing and implementing processing procedures for producing safe complementary foods in dynamic and unregulated food systems where common food staples are frequently contaminated with mycotoxins is challenging. This paper presents lessons about minimizing aflatoxins (AF) in groundnut flour and AF and/or fumonisins (FUM) in maize and groundnut pre-blended flour for complementary feeding in the context of a dietary research intervention in rural Tanzania. The flours were processed in collaboration with Halisi Products Limited (Halisi), a medium scale enterprise with experience in milling cereal-based flours in Arusha, Tanzania. Using a hazard analysis critical control point (HACCP) approach for quality assurance, two critical control points (CCPs) for AF in processing the pre-blended flour were identified: 1) screening maize before procurement, and 2) blending during the processing of each constituent flour. Blending of maize flour was also identified as a CCP for FUM. Visual inspection during screening and sorting were identified as important control measures for reducing AF, but these steps did not meet the criteria for a CCP due to lack of objective measurement and verifiable standards for AF. The HACCP approach enabled the production of low AF (<5 µg/kg) and FUM (<2 µg/g) flours with low rejection rates for the final products. The paper presents practical lessons that could be of value to a range of commercial processors in similar low- and middle-income contexts who are keen on improving food quality.

Chromothripsis-mediated small cell lung carcinoma.

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here we performed detailed clinicopathologic, genomic and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis - massive, localized chromosome shattering - recurrently involving chromosomes 11 or 12, and resulting in extrachromosomal (ecDNA) amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers.

Caries Experience of People with Cystic Fibrosis: A Systematic Review.

OBJECTIVES: Cystic Fibrosis is a multi-system disease, arising from a mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR). There is a lack of information regarding oral disease levels among people with cystic fibrosis. As part of an ongoing study assessing oral health in adults with cystic fibrosis at XXXXXXXXXX, a systematic review of available literature was conducted to ascertain the caries experience of people with cystic fibrosis. The objective was to systematically present and evaluate the literature comparing caries experience between people with cystic fibrosis and people without cystic fibrosis. METHODS: Five online databases were searched; Embase, Scopus, Web of Science Core Collection, Medline Ebsco and Cochrane Library. Studies that reported caries experience in people with cystic fibrosis were included in this review. RESULTS: The initial search identified 1199 publications from online databases. Twenty-one studies were included for qualitative analysis. Fourteen studies reported a lower caries experience in children with CF compared to children without CF, five studies reported a higher caries experience in adults with CF, and two studies found inconclusive evidence regarding the association between caries experience and CF status. All studies had a risk of bias that may influence results. CONCLUSION: Despite a lack of complete unanimity between all studies, there is a general trend that children with cystic fibrosis have a lower caries experience than their healthy counterparts, whereas adults with cystic fibrosis have a higher caries experience. The review highlights the need for further studies involving adults with cystic fibrosis as the majority of studies primarily consist of paediatric populations. CLINICAL SIGNIFICANCE: Dental practitioners should be aware that adults with cystic fibrosis have higher caries experience. Tailored approaches to dental care specific to cystic fibrosis individuals should be developed.

Functional profiling of CHAP domain-containing peptidoglycan hydrolases of Staphylococcus aureus USA300 uncovers potential targets for anti-staphylococcal therapies.

The bacterial pathogen Staphylococcus aureus employs a thick cell wall for protection against physical and chemical insults. This wall requires continuous maintenance to ensure strength and barrier integrity, but also to permit bacterial growth and division. The main cell wall component is peptidoglycan. Accordingly, the bacteria produce so-called peptidoglycan hydrolases (PGHs) that cleave glycan strands to facilitate growth, cell wall remodelling, separation of divided cells and release of exported proteins into the extracellular milieu. A special class of PGHs contains so-called 'cysteine, histidine-dependent amidohydrolase/peptidase' (CHAP) domains. In the present study, we profiled the roles of 11 CHAP PGHs encoded by the core genome of S. aureus USA300 LAC. Mutant strains lacking individual CHAP PGHs were analysed for growth, cell morphology, autolysis, and invasion and replication inside human lung epithelial cells. The results show that several investigated CHAP PGHs contribute to different extents to extracellular and intracellular growth and replication of S. aureus, septation of dividing cells, daughter cell separation once the division process is completed, autolysis and biofilm formation. In particular, the CHAP PGHs Sle1 and SAUSA300_2253 control intracellular staphylococcal replication and the resistance to ß-lactam antibiotics like oxacillin. This makes the S. aureus PGHs in general, and the Sle1 and SAUSA300_2253 proteins in particular, attractive targets for future prophylactic or therapeutic anti-staphylococcal interventions. Alternatively, these cell surface-exposed enzymes, or particular domains of these enzymes, could be applied in innovative anti-staphylococcal therapies.

Strict glucose control and elimination of NLRP3-induced inflammation prevents diabetic bladder dysfunction in the female Akita mouse model.

PURPOSE: Diabetic bladder dysfunction (DBD) is the most common diabetic complication. Logically, regulation of blood glucose should reverse dysfunction, but the Epidemiology of Diabetes Interventions and Complications study found strict control ineffective. However, it is possible that strict control may prevent DBD if initiated before symptoms appear. We examine the effect of early glucose control on development of DBD in the female diabetic Akita mouse (Type 1) and test the potential of inhibiting/deleting NLRP3 as adjunct therapy to glucose control. MATERIALS AND METHODS: Female Akita mice were bred NLRP3+/+ or NLRP3-/-. At 6 weeks of age, diabetics received either no glucose control or insulin pellets (s.c., Linshin) designed to poorly or strictly control blood glucose. At Week 15, blood glucose (glucometer), the extravasation potential of bladder (an indirect measurement of inflammation) and bladder function (urodynamics) were assessed. RESULTS: Blood glucose of diabetics was reduced in poorly controlled and strongly reduced in strictly controlled groups. Levels were not affected by deletion of NLRP3. Evans blue dye extravasation correlated with glucose control and was eliminated in the NLRP3-/- groups. Urodynamics found markers of overactivity in diabetics which was improved in the poorly controlled group and eliminated in the strictly controlled group. In the NLRP3-/- mice, no bladder dysfunction developed, regardless of glucose control. CONCLUSIONS: Early-initiated strict glycemic control and NLRP3 elimination can effectively prevent DBD, suggesting hyperglycemia acts through NLRP3-induced inflammation to trigger DBD.

Genomic prediction of regional-scale performance in switchgrass (Panicum virgatum) by accounting for genotype-by-environment variation and yield surrogate traits.

Switchgrass is a potential crop for bioenergy or carbon capture schemes, but further yield improvements through selective breeding are needed to encourage commercialization. To identify promising switchgrass germplasm for future breeding efforts, we conducted multi-site and multi-trait genomic prediction with a diversity panel of 630 genotypes from 4 switchgrass subpopulations (Gulf, Midwest, Coastal, and Texas), which were measured for spaced plant biomass yield across 10 sites. Our study focused on the use of genomic prediction to share information among traits and environments. Specifically, we evaluated the predictive ability of cross-validation (CV) schemes using only genetic data and the training set, (cross validation 1: CV1), a subset of the sites (cross validation 2: CV2), and/or with two yield surrogates (flowering time and fall plant height). We found that genotype-by-environment interactions were largely due to the north-south distribution of sites. The genetic correlations between yield surrogates and biomass yield were generally positive (mean height r=0.85; mean flowering time r=0.45) and did not vary due to subpopulation or growing region (North, Middle, South). Genomic prediction models had cross-validation predictive abilities of -0.02 for individuals using only genetic data (CV1) but 0.55, 0.69, 0.76, 0.81, and 0.84 for individuals with biomass performance data from one, two, three, four and five sites included in the training data (CV2), respectively. To simulate a resource-limited breeding program, we determined the predictive ability of models provided with: one site observation of flowering time (0.39), one site observation of flowering time and fall height (0.51), one site observation of fall height (0.52), one site observation of biomass (0.55), and five site observations of biomass yield (0.84). The ability to share information at a regional scale is very encouraging but further research is required to accurately translate spaced plant biomass to commercial-scale sward biomass performance.

Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.

Targeted therapy remains the future of anti-cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility. Here, ICT10336 is reported, a newly developed hypoxia-responsive prodrug of ATR inhibitor, AZD6738, which is hypoxia-activated and specifically releases AZD6738 only in hypoxic conditions, in vitro. This hypoxia-selective release of AZD6738 inhibited ATR activation (T1989 and S428 phosphorylation) and subsequently abrogated HIF1a-mediated adaptation of hypoxic cancers cells, thus selectively inducing cell death in 2D and 3D cancer models. Importantly, in normal tissues, ICT10336 is demonstrated to be metabolically stable and less toxic to normal cells than its active parent agent, AZD6738. In addition, ICT10336 exhibited a superior and efficient multicellular penetration ability in 3D tumor models, and selectively eradicated cells at the hypoxic core compared to AZD6738. In summary, the preclinical data demonstrate a new strategy of tumor-targeted delivery of ATR inhibitors with significant potential of enhancing the therapeutic index.

Intraspecific diploidization of a halophyte root fungus drives heterosis.

How organisms respond to environmental stress is a key topic in evolutionary biology. This study focused on the genomic evolution of Laburnicola rhizohalophila, a dark-septate endophytic fungus from roots of a halophyte. Chromosome-level assemblies were generated from five representative isolates from structured subpopulations. The data revealed significant genomic plasticity resulting from chromosomal polymorphisms created by fusion and fission events, known as dysploidy. Analyses of genomic features, phylogenomics, and macrosynteny have provided clear evidence for the origin of intraspecific diploid-like hybrids. Notably, one diploid phenotype stood out as an outlier and exhibited a conditional fitness advantage when exposed to a range of abiotic stresses compared with its parents. By comparing the gene expression patterns in each hybrid parent triad under the four growth conditions, the mechanisms underlying growth vigor were corroborated through an analysis of transgressively upregulated genes enriched in membrane glycerolipid biosynthesis and transmembrane transporter activity. In vitro assays suggested increased membrane integrity and lipid accumulation, as well as decreased malondialdehyde production under optimal salt conditions (0.3 M NaCl) in the hybrid. These attributes have been implicated in salinity tolerance. This study supports the notion that hybridization-induced genome doubling leads to the emergence of phenotypic innovations in an extremophilic endophyte.

Small molecule substrates for the rapid quantification of acyl transfer activity of nylon hydrolase NylCA.

The widespread use of polyamides such as nylons has led to the accumulation of nylon waste, which is particularly resistant to decomposition due to the intrinsic stability of the amide bond. New methods are required for the true recycling of these waste materials by depolymerization. Enzymes that are capable of hydrolyzing polyamides have been proposed as biocatalysts that may be suitable for this application. NylC is an enzyme that can mediate the hydrolysis of aminohexanoic acid oligomers, and to some extent, bulk polymers. However, current assays to characterize the activity of this enzyme require long reaction times and/or rely on secondary reactions to quantify hydrolysis. Herein, we have designed structurally-optimized small molecule chromogenic esters that serve as substrate analogues for monitoring NylC acyltransferase activity in a continuous manner. This assay can be performed in minutes at room temperature, and the substrate N-acetyl-GABA-pNP ester (kcat = 0.37 s-1, KM = 256 µM) shows selectivity for NylC in complex biological media. We also demonstrate that activity towards this substrate analogue correlates with amide hydrolysis, which is the primary activity of this enzyme. Furthermore, our screening of substrate analogues provides insight into the substrate specificity of NylC, which is relevant to biocatalytic applications.

The DNA repair kinase ATM regulates CD13 expression and cell migration.

Classically, ATM is known for its role in sensing double-strand DNA breaks, and subsequently signaling for their repair. Non-canonical roles of ATM include transcriptional silencing, ferroptosis, autophagy and angiogenesis. Angiogenesis mediated by ATM signaling has been shown to be VEGF-independent via p38 signaling. Independently, p38 signaling has been shown to upregulate metalloproteinase expression, including MMP-2 and MMP-9, though it is unclear if this is linked to ATM. Here, we demonstrate ATM regulates aminopeptidase-N (CD13/APN/ANPEP) at the protein level. Positive correlation was seen between ATM activity and CD13 protein expression using both "wildtype" (WT) and knockout (KO) ataxia telangiectasia (AT) cells through western blotting; with the same effect shown when treating neuroblastoma cancer cell line SH-SY5Y, as well as AT-WT cells, with ATM inhibitor (ATMi; KU55933). However, qPCR along with publically available RNAseq data from Hu et al. (J. Clin. Invest., 2021, 131, e139333), demonstrated no change in mRNA levels of CD13, suggesting that ATM regulates CD13 levels via controlling protein degradation. This is further supported by the observation that incubation with proteasome inhibitors led to restoration of CD13 protein levels in cells treated with ATMi. Migration assays showed ATM and CD13 inhibition impairs migration, with no additional effect observed when combined. This suggests an epistatic effect, and that both proteins may be acting in the same signaling pathway that influences cell migration. This work indicates a novel functional interaction between ATM and CD13, suggesting ATM may negatively regulate the degradation of CD13, and subsequently cell migration.

Specialized pro-resolution mediators in the bladder: effects of resolvin E1 on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.

BACKGROUND: One of the most common, but least studied, diabetic complication is diabetic bladder dysfunction. Current therapies include glucose control and symptom-based interventions. However, efficacy of these therapies is mixed and often have undesirable side effects. Diabetes is now known to be a chronic inflammatory disease. Specialized pro-resolving mediators are a class of compounds that promote the resolution of inflammation and have been shown to be effective in treating chronic inflammatory conditions. In this study we examine the ability of resolvin E1 to improve signs of diabetic bladder dysfunction. METHODS: Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice. RESULTS: Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan's blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks. CONCLUSIONS: Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.

Evaluation of copromicroscopy, multiplex-qPCR and antibody serology for monitoring of human ascariasis in endemic settings.

BACKGROUND: The standard diagnosis of Ascaris lumbricoides and other soil-transmitted helminth (STH) infections relies on the detection of worm eggs by copromicroscopy. However, this method is dependent on worm patency and shows only limited accuracy in low-intensity infection settings. We aimed to decipher the diagnostic accuracy of different antibodies using various Ascaris antigens in reference to copromicroscopy and quantitative PCR (qPCR), four months after national STH preventative chemotherapy among school children in western Kenya. METHODOLOGY: STH infection status of 390 school children was evaluated via copromicroscopy (Kato-Katz and mini-FLOTAC) and qPCR. In parallel, Ascaris-specific antibody profiles against larval and adult worm lysates, and adult worm excretory-secretory (ES) products were determined by enzyme-linked immunosorbent assay. Antibody cross-reactivity was evaluated using the closely related zoonotic roundworm species Toxocara cati and Toxocara canis. The diagnostic accuracy of each antibody was evaluated using receiver operating curve analysis and the correspondent area under the curve (AUC). PRINCIPAL FINDINGS: Ascaris was the predominant helminth infection with an overall prevalence of 14.9% (58/390). The sensitivity of mini-FLOTAC and Kato-Katz for Ascaris diagnosis reached only 53.5% and 63.8%, respectively compared to qPCR. Although being more sensitive, qPCR values correlated with microscopic egg counts (R = -0.71, P<0.001), in contrast to antibody levels. Strikingly, IgG antibodies recognizing the ES products of adult Ascaris worms reliably diagnosed active Ascaris infection as determined by qPCR and microscopy, with IgG1 displaying the highest accuracy (AUC = 0.83, 95% CI: 0.75-0.91). CONCLUSION: IgG1 antibody responses against adult Ascaris-ES products hold a promising potential for complementing the standard fecal and molecular techniques employed for monitoring Ascaris infections. This is of particular importance in the context of deworming programs as the antibody diagnostic accuracy was independent of egg counts.

The Amount and Pattern of Reciprocal Compensations Predict Performance Stability in a Visually Guided Finger Force Production Task.

Previous work suggests that synergistic activity among motor elements implicated in force production tasks underlies enhanced performance stability associated with visual feedback. A hallmark of synergistic activity is reciprocal compensation, that is, covariation in the states of motor elements that stabilizes critical performance variables. The present study examined if characteristics of reciprocal compensation are indicators of individuals' capacity to respond adaptively to variations in the resolution of visual feedback about criterion performance. Twenty healthy adults (19.25 ± 1.25 years; 15 females and five males) pressed two sensors with their index fingers to produce a total target force equivalent to 20% of their maximal voluntary contraction under nine conditions that differed in the spatial resolution of real-time feedback about their performance. By combining within-trial uncontrolled manifold and sample entropy analyses, we quantified the amount and degree of irregularity (i.e., non-repetitiveness) of reciprocal compensations over time. We found a U-shaped relationship between performance stability and gain. Importantly, this relationship was moderated by the degree of irregularity of reciprocal compensation. Lower irregularity in reciprocal compensation patterns was related to individuals' capacity to maintain (or minimize losses in) performance under changes in feedback resolution. Results invite future investigation into how interindividual variations in reciprocal compensation patterns relate to differences in control strategies supporting adaptive responses in complex, visually guided motor tasks.

Selection against domestication alleles in introduced rabbit populations.

Humans have moved domestic animals around the globe for thousands of years. These have occasionally established feral populations in nature, often with devastating ecological consequences. To understand how natural selection shapes re-adaptation into the wild, we investigated one of the most successful colonizers in history, the European rabbit. By sequencing the genomes of 297 rabbits across three continents, we show that introduced populations exhibit a mixed wild-domestic ancestry. We show that alleles that increased in frequency during domestication were preferentially selected against in novel natural environments. Interestingly, causative mutations for common domestication traits sometimes segregate at considerable frequencies if associated with less drastic phenotypes (for example, coat colour dilution), whereas mutations that are probably strongly maladaptive in nature are absent. Whereas natural selection largely targeted different genomic regions in each introduced population, some of the strongest signals of parallelism overlap genes associated with neuronal or brain function. This limited parallelism is probably explained by extensive standing genetic variation resulting from domestication together with the complex mixed ancestry of introduced populations. Our findings shed light on the selective and molecular mechanisms that enable domestic animals to re-adapt to the wild and provide important insights for the mitigation and management of invasive populations.

AMP-RNNpro: a two-stage approach for identification of antimicrobials using probabilistic features.

Antimicrobials are molecules that prevent the formation of microorganisms such as bacteria, viruses, fungi, and parasites. The necessity to detect antimicrobial peptides (AMPs) using machine learning and deep learning arises from the need for efficiency to accelerate the discovery of AMPs, and contribute to developing effective antimicrobial therapies, especially in the face of increasing antibiotic resistance. This study introduced AMP-RNNpro based on Recurrent Neural Network (RNN), an innovative model for detecting AMPs, which was designed with eight feature encoding methods that are selected according to four criteria: amino acid compositional, grouped amino acid compositional, autocorrelation, and pseudo-amino acid compositional to represent the protein sequences for efficient identification of AMPs. In our framework, two-stage predictions have been conducted. Initially, this study analyzed 33 models on these feature extractions. Then, we selected the best six models from these models using rigorous performance metrics. In the second stage, probabilistic features have been generated from the selected six models in each feature encoding and they are aggregated to be fed into our final meta-model called AMP-RNNpro. This study also introduced 20 features with SHAP, which are crucial in the drug development fields, where we discover AAC, ASDC, and CKSAAGP features are highly impactful for detection and drug discovery. Our proposed framework, AMP-RNNpro excels in the identification of novel Amps with 97.15% accuracy, 96.48% sensitivity, and 97.87% specificity. We built a user-friendly website for demonstrating the accurate prediction of AMPs based on the proposed approach which can be accessed at http://13.126.159.30/ .

Discovery and characterization of dietary antigens in oral tolerance.

Food antigens elicit immune tolerance through the action of regulatory T cells (Tregs) in the intestine. Although antigens that trigger common food allergies are known, the epitopes that mediate tolerance to most foods have not been described. Here, we identified murine T cell receptors specific for maize, wheat, and soy, and used expression cloning to de-orphan their cognate epitopes. All of the epitopes derive from seed storage proteins that are resistant to degradation and abundant in the edible portion of the plant. Multiple unrelated T cell clones were specific for an epitope at the C-terminus of 19 kDa alpha-zein, a protein from maize kernel. An MHC tetramer loaded with this antigen revealed that zein-specific T cells are predominantly Tregs localized to the intestine. These cells, which develop concurrently with weaning, constitute up to 2% of the peripheral Treg pool. Bulk and single-cell RNA sequencing revealed that these cells express higher levels of immunosuppressive markers and chemokines compared to other Tregs. These data suggest that immune tolerance to plant-derived foods is focused on a specific class of antigens with common features, and they reveal the functional properties of naturally occurring food-specific Tregs.

Characteristics and outcomes of patients with symptomatic chronic myocardial injury in a Tanzanian emergency department: A prospective observational study.

BACKGROUND: Chronic myocardial injury is a condition defined by stably elevated cardiac biomarkers without acute myocardial ischemia. Although studies from high-income countries have reported that chronic myocardial injury predicts adverse prognosis, there are no published data about the condition in sub-Saharan Africa. METHODS: Between November 2020 and January 2023, adult patients with chest pain or shortness of breath were recruited from an emergency department in Moshi, Tanzania. Medical history and point-of-care troponin T (cTnT) assays were obtained from participants; those whose initial and three-hour repeat cTnT values were abnormally elevated but within 11% of each other were defined as having chronic myocardial injury. Mortality was assessed thirty days following enrollment. RESULTS: Of 568 enrolled participants, 81 (14.3%) had chronic myocardial injury, 73 (12.9%) had acute myocardial injury, and 412 (72.5%) had undetectable cTnT values. Of participants with chronic myocardial injury, the mean (± sd) age was 61.5 (± 17.2) years, and the most common comorbidities were CKD (n = 65, 80%) and hypertension (n = 60, 74%). After adjusting for CKD, thirty-day mortality rates (38% vs. 36%, aOR 1.03, 95% CI: 0.52-2.03, p = 0.931) were similar between participants with chronic myocardial injury and those with acute myocardial injury, but significantly greater (38% vs. 13.6%, aOR 3.63, 95% CI: 1.98-6.65, p<0.001) among participants with chronic myocardial injury than those with undetectable cTnT values. CONCLUSION: In Tanzania, chronic myocardial injury is a poor prognostic indicator associated with high risk of short-term mortality. Clinicians practicing in this region should triage patients with stably elevated cTn levels in light of their increased risk.