Glyphosate: Hepatotoxicity, Nephrotoxicity, Hemotoxicity, Carcinogenicity, and Clinical Cases of Endocrine, Reproductive, Cardiovascular, and Pulmonary System Intoxication.

Glyphosate (GLP) is an active agent of GLP-based herbicides (GBHs), i.e., broad-spectrum and postemergent weedkillers, commercialized by Monsanto as, e.g., Roundup and RangerPro formulants. The GBH crop spraying, dedicated to genetically engineered GLP-resistant crops, has revolutionized modern agriculture by increasing the production yield. However, abusively administered GBHs' ingredients, e.g., GLP, polyoxyethyleneamine, and heavy metals, have polluted environmental and industrial areas far beyond farmlands, causing global contamination and life-threatening risk, which has led to the recent local bans of GBH use. Moreover, preclinical and clinical reports have demonstrated harmful impacts of GLP and other GBH ingredients on the gut microbiome, gastrointestinal tract, liver, kidney, and endocrine, as well as reproductive, and cardiopulmonary systems, whereas carcinogenicity of these herbicides remains controversial. Occupational exposure to GBH dysregulates the hypothalamic-pituitary-adrenal axis, responsible for steroidogenesis and endocrinal secretion, thus affecting hormonal homeostasis, functions of reproductive organs, and fertility. On the other hand, acute intoxication with GBH, characterized by dehydration, oliguria, paralytic ileus, as well as hypovolemic and cardiogenic shock, pulmonary edema, hyperkalemia, and metabolic acidosis, may occur fatally. As no antidote has been developed for GBH poisoning so far, the detoxification is mainly symptomatic and supportive and requires intensive care based on gastric lavage, extracorporeal blood filtering, and intravenous lipid emulsion infusion. The current review comprehensively discusses the molecular and physiological basics of the GLP- and/or GBH-induced diseases of the endocrine and reproductive systems, and cardiopulmonary-, nephro-, and hepatotoxicities, presented in recent preclinical studies and case reports on the accidental or intentional ingestions with the most popular GBHs. Finally, they briefly describe modern and future healthcare methods and tools for GLP detection, determination, and detoxification. Future electronically powered, decision-making, and user-friendly devices targeting major GLP/GBH's modes of actions, i.e., dysbiosis and the inhibition of AChE, shall enable self-handled or point-of-care professional-assisted evaluation of the harm followed with rapid capturing GBH xenobiotics in the body and precise determining the GBH pathology-associated biomarkers levels.

Rapid metabolic regulation of a novel arginine methylation of KCa3.1 attenuates T cell exhaustion.

T cell exhaustion is linked to persistent antigen exposure and perturbed activation events, correlating with poor disease prognosis. Tumor-mediated T cell exhaustion is well documented; however, how the nutrient-deprived tumor niche affects T cell receptor (TCR) activation is largely unclear. We show that methionine metabolism licenses optimal TCR signaling by regulating the protein arginine methylome, and limiting methionine availability during early TCR signaling promotes subsequent T cell exhaustion. We discovered a novel arginine methylation of a Ca 2+ -activated potassium transporter, KCa3.1, prevention of which results in increased Ca 2+ -mediated NFAT1 activation, NFAT1 promoter occupancy, and T cell exhaustion. Furthermore, methionine supplementation reduces nuclear NFAT1 in tumor-infiltrating T cells and augments their anti-tumor activity. These findings demonstrate metabolic regulation of T cell exhaustion determined during TCR engagement.

Idiopathic pulmonary fibrosis (IPF): Diagnostic routes using novel biomarkers.

Idiopathic pulmonary fibrosis (IPF) diagnosis is still the diagnosis of exclusion. Differentiating from other forms of interstitial lung diseases (ILDs) is essential, given the various therapeutic approaches. The IPF course is now unpredictable for individual patients, although some genetic factors and several biomarkers have already been associated with various IPF prognoses. Since its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. The present review critically examines the recent literature on molecular biomarkers potentially useful in IPF diagnostics. The examined biomarkers are grouped into breath and sputum biomarkers, serologically assessed extracellular matrix neoepitope markers, and oxidative stress biomarkers in lung tissue. Fibroblasts and complete blood count have also gained recent interest in that respect. Although several biomarker candidates have been profiled, there has yet to be a single biomarker that proved specific to the IPF disease. Nevertheless, various IPF biomarkers have been used in preclinical and clinical trials to verify their predictive and monitoring potential.

Single-, Dual-, and Multi-Stimuli-Responsive Nanogels for Biomedical Applications.

In recent years, stimuli-responsive nanogels that can undergo suitable transitions under endogenous (e.g., pH, enzymes and reduction) or exogenous stimuli (e.g., temperature, light, and magnetic fields) for on-demand drug delivery, have received significant interest in biomedical fields, including drug delivery, tissue engineering, wound healing, and gene therapy due to their unique environment-sensitive properties. Furthermore, these nanogels have become very popular due to some of their special properties such as good hydrophilicity, high drug loading efficiency, flexibility, and excellent biocompatibility and biodegradability. In this article, the authors discuss current developments in the synthesis, properties, and biomedical applications of stimulus-responsive nanogels. In addition, the opportunities and challenges of nanogels for biomedical applications are also briefly predicted.

Glyphosate: Impact on the microbiota-gut-brain axis and the immune-nervous system, and clinical cases of multiorgan toxicity.

Glyphosate (GLP) and GLP-based herbicides (GBHs), such as polyethoxylated tallow amine-based GLP surfactants (GLP-SH), developed in the late 70', have become the most popular and controversial agrochemicals ever produced. Nowadays, GBHs have reached 350 million hectares of crops in over 140 countries, with an annual turnover of 5 billion and 11 billion USD in the U.S.A. and worldwide, respectively. Because of the highly efficient inhibitory activity of GLP targeted to the 5-enolpyruvylshikimate-3-phosphate synthase pathway, present in plants and several bacterial strains, the GLP-resistant crop-based genetic agricultural revolution has decreased famine and improved the costs and quality of living in developing countries. However, this progress has come at the cost of the 50-year GBH overuse, leading to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide farm and companies' workers. According to preclinical and clinical studies covered in the present review, poisoning with GLP, GLP-SH, and GBHs devastatingly affects gut microbiota and the microbiota-gut-brain (MGB) axis, leading to dysbiosis and gastrointestinal (GI) ailments, as well as immunosuppression and inappropriate immunostimulation, cholinergic neurotransmission dysregulation, neuroendocrinal system disarray, and neurodevelopmental and neurobehavioral alterations. Herein, we mainly focus on the contribution of gut microbiota (GM) to neurological impairments, e.g., stroke and neurodegenerative and neuropsychiatric disorders. The current review provides a comprehensive introduction to GLP's microbiological and neurochemical activities, including deviation of the intestinal Firmicutes-to-Bacteroidetes ratio, acetylcholinesterase inhibition, excitotoxicity, and mind-altering processes. Besides, it summarizes and critically discusses recent preclinical studies and clinical case reports concerning the harmful impacts of GBHs on the GI tract, MGB axis, and nervous system. Finally, an insightful comparison of toxic effects caused by GLP, GBH-SH, and GBHs is presented. To this end, we propose a first-to-date survey of clinical case reports on intoxications with these herbicides.

A novel cardiac magnetic resonance-based personalized risk stratification model in dilated cardiomyopathy: a prospective study.

OBJECTIVES: To explore individual weight of cardiac magnetic resonance (CMR) metrics to predict mid-term outcomes in patients with dilated cardiomyopathy (DCM), and develop a risk algorithm for mid-term outcome based on CMR biomarkers. MATERIALS AND METHODS: Patients with DCM who underwent CMR imaging were prospectively enrolled in this study. The primary endpoint was a composite of heart failure (HF) death, sudden cardiac death (SCD), aborted SCD, and heart transplantation. RESULTS: A total of 407 patients (age 48.1 ± 13.8 years, 331 men) were included in the final analysis. During a median follow-up of 21.7 months, 63 patients reached the primary endpoint. NYHA class III/IV (HR = 2.347 [1.073-5.133], p = 0.033), left ventricular ejection fraction (HR = 0.940 [0.909-0.973], p < 0.001), late gadolinium enhancement (LGE) > 0.9% and ≤ 6.6% (HR = 3.559 [1.020-12.412], p = 0.046), LGE > 6.6% (HR = 6.028 [1.814-20.038], p = 0.003), and mean extracellular volume (ECV) fraction ≥ 32.8% (HR = 5.922 [2.566-13.665], p < 0.001) had a significant prognostic association with the primary endpoints (C-statistic: 0.853 [0.810-0.896]). Competing risk regression analyses showed that patients with mean ECV fraction ≥ 32.8%, LGE ≥ 5.9%, global circumferential strain ≥ - 5.6%, or global longitudinal strain ≥ - 7.3% had significantly shorter event-free survival due to HF death and heart transplantation. Patients with mean ECV fraction ≥ 32.8% and LGE ≥ 5.9% had significantly shorter event-free survival due to SCD or aborted SCD. CONCLUSION: ECV fraction may be the best independently risk factor for the mid-term outcomes in patients with DCM, surpassing LVEF and LGE. LGE has a better prognostic value than other CMR metrics for SCD and aborted SCD. The risk stratification model we developed may be a promising non-invasive tool for decision-making and prognosis. CLINICAL RELEVANCE STATEMENT: "One-stop" assessment of cardiac function and myocardial characterization using cardiac magnetic resonance might improve risk stratification of patients with DCM. In this prospective study, we propose a novel risk algorithm in DCM including NYHA functional class, LVEF, LGE, and ECV. KEY POINTS: • The present study explores individual weight of CMR metrics for predicting mid-term outcomes in dilated cardiomyopathy. • We have developed a novel risk algorithm for dilated cardiomyopathy that includes cardiac functional class, ejection fraction, late gadolinium enhancement, and extracellular volume fraction. • Personalized risk model derived by CMR contributes to clinical assessment and individual decision-making.

Improving the Selectivity of the C-C Coupled Product Electrosynthesis by Using Molecularly Imprinted Polymer─An Enhanced Route from Phenol to Biphenol.

We developed a procedure for selective 2,4-dimethylphenol, DMPh, direct electro-oxidation to 3,3',5,5'-tetramethyl-2,2'-biphenol, TMBh, a C-C coupled product. For that, we used an electrode coated with a product-selective molecularly imprinted polymer (MIP). The procedure is reasonably selective toward TMBh without requiring harmful additives or elevated temperatures. The TMBh product itself was used as a template for imprinting. We followed the template interaction with various functional monomers (FMs) using density functional theory (DFT) simulations to select optimal FM. On this basis, we used a prepolymerization complex of TMBh with carboxyl-containing FM at a 1:2 TMBh-to-FM molar ratio for MIP fabrication. The template-FM interaction was also followed by using different spectroscopic techniques. Then, we prepared the MIP on the electrode surface in the form of a thin film by the potentiodynamic electropolymerization of the chosen complex and extracted the template. Afterward, we characterized the fabricated films by using electrochemistry, FTIR spectroscopy, and AFM, elucidating their composition and morphology. Ultimately, the DMPh electro-oxidation was performed on the MIP film-coated electrode to obtain the desired TMBh product. The electrosynthesis selectivity was much higher at the electrode coated with MIP film in comparison with the reference nonimprinted polymer (NIP) film-coated or bare electrodes, reaching 39% under optimized conditions. MIP film thickness and electrosynthesis parameters significantly affected the electrosynthesis yield and selectivity. At thicker films, the yield was higher at the expense of selectivity, while the electrosynthesis potential increase enhanced the TMBh product yield. Computer simulations of the imprinted cavity interaction with the substrate molecule demonstrated that the MIP cavity promoted direct coupling of the substrate to form the desired TMBh product.

Glyphosate Separating and Sensing for Precision Agriculture and Environmental Protection in the Era of Smart Materials.

The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based herbicides (GBHs) traditionally used in agriculture over the past decades. Commercialized in 1974, GBHs have now reached 350 million hectares of crops in over 140 countries with an annual turnover of 11 billion USD worldwide. However, rolling exploitation of GLP and GBHs in the last decades has led to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide of farm and companies' workers. Intoxication with these herbicides dysregulates the microbiome-gut-brain axis, cholinergic neurotransmission, and endocrine system, causing paralytic ileus, hyperkalemia, oliguria, pulmonary edema, and cardiogenic shock. Precision agriculture, i.e., an (information technology)-enhanced approach to crop management, including a site-specific determination of agrochemicals, derives from the benefits of smart materials (SMs), data science, and nanosensors. Those typically feature fluorescent molecularly imprinted polymers or immunochemical aptamer artificial receptors integrated with electrochemical transducers. Fabricated as portable or wearable lab-on-chips, smartphones, and soft robotics and connected with SM-based devices that provide machine learning algorithms and online databases, they integrate, process, analyze, and interpret massive amounts of spatiotemporal data in a user-friendly and decision-making manner. Exploited for the ultrasensitive determination of toxins, including GLP, they will become practical tools in farmlands and point-of-care testing. Expectedly, smart sensors can be used for personalized diagnostics, real-time water, food, soil, and air quality monitoring, site-specific herbicide management, and crop control.

Electroactive molecularly imprinted polymer nanoparticles for selective glyphosate determination.

Redox-active molecularly imprinted polymer nanoparticles selective for glyphosate, MIP-Gly NPs, were devised, synthesized, and subsequently integrated onto platinum screen-printed electrodes (Pt-SPEs) to fabricate a chemosensor for selective determination of glyphosate (Gly) without the need for redox probe in the test solution. That was because, ferrocenylmethyl methacrylate was added to the polymerization mixtures during the NPs synthesis so that the resulting MIP-Gly NPs contained covalently immobilized ferrocenyl moieties as the reporting redox ingredient, conferring these NPs with electroactive properties. MIP-Gly NPs of four different compositions were evaluated. The herein described approach represents a simple and effective way to endow MIP NPs with electrochemical reporting capabilities with neither the need to functionalize them post-synthesis nor to use electrochemical mediators present in the tested solution during the analyte determinations. MIP-Gly NPs synthesized using allylamine and squaramide-based monomers appeared most selective to Gly. The Pt-SPEs modified with MIP-Gly NPs were characterized with differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Changes in the DPV peak originating from the oxidation of the ferrocenyl moieties in these MIP-Gly NPs served as the analytical signal. The DPV limit of detection and the linear dynamic concentration range for Gly were 3.7 pM and 25 pM-500 pM, respectively. Moreover, the selectivity of the fabricated chemosensors was sufficiently high to determine Gly successfully in spiked river water samples.

Australian Consumers' Attitudes towards Sustainable Diet Practices Regarding Food Waste, Food Processing, and the Health Aspects of Diet: A Cross Sectional Survey.

Environmentally sustainable diets are increasingly aspired to in food-based dietary guidelines across the world. However, little is known about consumer attitudes toward these diets when making food decisions. This study aimed to identify the demographic characteristics of Australian adults based on the level of attention they paid to the healthfulness of their diet, their consideration of the level of food processing, and their concern about household food waste and sustainable packaging disposal. Adults aged from 18 to over 75 years (n = 540) were surveyed online. Thirty-seven percent were concerned about sustainable food waste, 28% considered the level of food processing when making food decisions, and 23% paid attention to the healthfulness of the food they ate. Adults who had higher educational attainment (above Year 12) were twice as likely to be concerned about food waste and sustainable packaging disposal (odds ratio (OR) = 2.10, 95% confidence interval (CI) 1.29-3.4), and processing levels (OR = 2.04, 95% CI 1.23-3.42) (controlling for age and gender). Those earning an income over AUD$100,000 were twice as likely to pay attention to the healthfulness of their food choices than those earning less than AUD$50,000 (OR = 2.19, 95% CI 1.28-3.74). Only 9% percent were concerned about or paid attention to all three of the components of healthy sustainable diets investigated, and 45% paid no attention and were not concerned about all three components. These findings suggest there is a need to educate the public to raise awareness of and concern for healthy, minimally processed, and sustainable food choices.

Post-imprinting modification: electrochemical and scanning electrochemical microscopy studies of a semi-covalently surface imprinted polymer.

Herein we described a post-imprinting modification of the imprinted molecular cavities for electrochemical sensing of a target protein. Imprinted molecular cavities were generated by following the semi-covalent surface imprinting approach. These mesoporous cavities were modified with a ferrocene 'electrochemical' tracer for electrochemical transduction of the target protein recognition. Electrochemical sensors prepared after post-imprinting modification showed a linear response in the concentration range of 0.5 to 50 µM. Chemosensors fabricated based on capacitive impedimetric transduction demonstrated that imprinted molecular cavities without post-imprinting modification showed better selectivity. Scanning electrochemical microscopy (SECM) was used for the surface characterization of imprinted molecular cavities modified with ferrocene electrochemical tracers. SECM analysis performed in the feedback mode monitor changes in the surface state of the ferrocene-modified polymer film. The kinetics of the mediator regeneration was almost 1.8 times higher on the non-imprinted surface versus the post-imprinting modified molecular imprinted polymer.

Enumerating Stable Nanopores in Graphene and Their Geometrical Properties Using the Combinatorics of Hexagonal Lattices.

Nanopores in two-dimensional (2D) materials, including graphene, can be used for a variety of applications, such as gas separations, water desalination, and DNA sequencing. So far, however, all plausible isomeric shapes of graphene nanopores have not been enumerated. Instead, a probabilistic approach has been followed to predict nanopore shapes in 2D materials, due to the exponential increase in the number of nanopores as the size of the vacancy increases. For example, there are 12 possible isomers when N = 6 atoms are removed, a number that theoretically increases to 11.7 million when N = 20 atoms are removed from the graphene lattice. In this regard, the development of a smaller, exhaustive data set of stable nanopore shapes can help future experimental and theoretical studies focused on using nanoporous 2D materials in various applications. In this work, we use the theory of 2D triangular "lattice animals" to create a library of all stable graphene nanopore shapes based on a modification of a well-known algorithm in the mathematical combinatorics of polyforms known as Redelmeier's algorithm. We show that there exists a correspondence between graphene nanopores and triangular polyforms (called polyiamonds) as well as hexagonal polyforms (called polyhexes). We develop the concept of a polyiamond ID to identify unique nanopore isomers. We also use concepts from polyiamond and polyhex geometries to eliminate unstable nanopores containing dangling atoms, bonds, and moieties. We verify using density functional theory calculations that such pores are indeed unstable. The exclusion of these unstable nanopores leads to a remarkable reduction in the possible nanopores from 11.7 million for N = 20 to only 0.184 million nanopores, thereby indicating that the number of stable nanopores is almost 2 orders of magnitude lower and is much more tractable. Not only that, by extracting the polyhex outline, our algorithm allows searching for nanopores with dimensions and shape factors in a specified range, thus aiding the design of the geometrical properties of nanopores for specific applications. We also provide the coordinate files of the stable nanopores as a library to facilitate future theoretical studies of these nanopores.

In-Capillary Photodeposition of Glyphosate-Containing Polyacrylamide Nanometer-Thick Films.

The present research reports on in-water, site-specific photodeposition of glyphosate (GLP)-containing polyacrylamide (PAA-GLP) nanometer-thick films (nanofilms) on an inner surface of fused silica (fused quartz) microcapillaries presilanized with trimethoxy(octen-7-yl)silane (TMOS). TMOS was chosen because of the vinyl group presence in its structure, enabling its participation in the (UV light)-activated free-radical polymerization (UV-FRP) after its immobilization on a fused silica surface. The photodeposition was conducted in an aqueous (H2O/ACN; 3:1, v/v) solution, using UV-FRP (λ = 365 nm) of the acrylamide (AA) functional monomer, the N,N'-methylenebis(acrylamide) (BAA) cross-linking monomer, GLP, and the azobisisobutyronitrile (AIBN) UV-FRP initiator. Acetonitrile (ACN) was used as the porogen and the solvent to dissolve monomers and GLP. Because of the micrometric diameters of microcapillaries, the silanization and photodeposition procedures were first optimized on fused silica slides. The introduction of TMOS, as well as the formation of PAA and PAA-GLP nanofilms, was determined using atomic force microscopy (AFM), scanning electron microscopy with energy-dispersive X-ray (SEM-EDX) spectroscopy, and confocal micro-Raman spectroscopy. Particularly, AFM and SEM-EDX measurements determined nanofilms' thickness and GLP content, respectively, whereas in-depth confocal (micro-Raman spectroscopy)-assisted imaging of PAA- and PAA-GLP-coated microcapillary inner surfaces confirmed the successful photodeposition. Moreover, we examined the GLP impact on polymer gelation by monitoring hydration in a hydrogel and a dried powder PAA-GLP. Our study demonstrated the usefulness of the in-capillary micro-Raman spectroscopy imaging and in-depth profiling of GLP-encapsulated PAA nanofilms. In the future, our simple and inexpensive procedure will enable the fabrication of polymer-based microfluidic chemosensors or adsorptive-separating devices for GLP detection, determination, and degradation.

Cardiac MRI Risk Stratification for Dilated Cardiomyopathy with Left Ventricular Ejection Fraction of 35% or Higher.

Background Studies over the past 15 years have demonstrated that a considerable number of patients with dilated cardiomyopathy (DCM) who died from sudden cardiac death (SCD) had a left ventricular (LV) ejection fraction (LVEF) of 35% or higher. Purpose To identify clinical and cardiac MRI risk factors for adverse events in patients with DCM and LVEF of 35% or higher. Materials and Methods In this retrospective study, consecutive patients with DCM and LVEF of 35% or higher who underwent cardiac MRI between January 2010 and December 2017 were included. The primary end point was a composite of SCD or aborted SCD. The secondary end point was a composite of all-cause mortality, heart transplant, or hospitalization for heart failure. The risk factors for the primary and secondary end points were identified with multivariable Cox analysis. Results A total of 466 patients with DCM and LVEF of 35% or higher (mean age, 44 years ± 14 [SD]; 358 men) were included. During a mean follow-up of 79 months ± 30 (SD) (range, 7-143 months), 40 patients reached the primary end point and 61 reached the secondary end point. In the adjusted analysis, age (hazard ratio [HR], 1.03 per year [95% CI: 1.00, 1.05]; P = .04), family history of SCD (HR, 3.4 [95% CI: 1.3, 8.8]; P = .01), New York Heart Association (NYHA) class III or IV (HR vs NYHA class I or II, 2.1 [95% CI: 1.1, 3.9]; P = .02), and myocardial scar at late gadolinium enhancement (LGE) MRI greater than or equal to 7.1% of the LV mass (HR, 4.4 [95% CI: 2.4, 8.3]; P < .001) were associated with SCD or aborted SCD. For the composite secondary end point, LGE greater than or equal to 7.1% of the LV mass (HR vs LGE <7.1%, 2.0 [95% CI: 1.2, 3.4]; P = .01), left atrial maximum volume index, and reduced global longitudinal strain were independent predictors. Conclusion For patients with dilated cardiomyopathy and left ventricular (LV) ejection fraction of 35% or higher, cardiac MRI-defined myocardial scar greater than or equal to 7.1% of the LV mass was associated with sudden cardiac death (SCD) or aborted SCD. © RSNA, 2022 Online supplemental material is available for this article.

Clinical features, myocardial strain and tissue characteristics of heart failure with preserved ejection fraction in patients with obesity: A prospective cohort study.

Background: The pathophysiology and subsequent myocardial dysfunction of heart failure with preserved ejection fraction (HFpEF) with comorbid obesity has not been extensively described. This study aimed to investigate the clinical features and cardiovascular magnetic resonance (CMR) derived myocardial strain and tissue characteristics in patients with HFpEF and comorbid obesity phenotype. Methods: In this prospective cohort study, we included consecutive patients admitted to Fuwai hospital in China who underwent CMR. Patients with HFpEF or obesity were diagnosed with demographic data, clinical presentation, laboratory test, and echocardiography or CMR imaging. The key exclusion criteria were cardiomyopathy, primary valvular heart disease, and significant coronary artery disease. Participant data were obtained from the electronic medical records database or inquiry. Comparisons of clinical features and CMR derived structural and functional parameters amongst different groups were made using one-way analysis of variance, or χ2 tests, and post hoc Bonferroni analysis where appropriate. Findings: Between January 1, 2019 and July 31, 2021, 280 participants (108 patients with HFpEF and obesity, 50 patients with HFpEF and normal weight, 72 patients with obesity, and 50 healthy controls) were enrolled. Compared with patients with HFpEF and normal weight, patients with HFpEF and obesity were younger males, and had higher plasma volume, uric acid and hemoglobin levels, yet less often atrial fibrillation, and lower NT-proBNP levels, and had higher left ventricular mass index, end-diastole/systole volume index, lower left atrial volume index, and worse myocardial strains (all p ≤ 0.05), but no remarkable difference in late gadolinium enhancement (LGE) presence and extracellular volume fraction (ECV). After adjusting for age, atrial fibrillation, and coronary artery disease, only global longitudinal strain (GLS, p = 0.031) and early-diastolic global longitudinal strain rate (eGLSR, p = 0.043) were considerably worse in patients with HFpEF and obesity versus patients with HFpEF and normal weight. Furthermore, early-diastolic strain rates showed no linear association with ECV in patients with HFpEF and obesity. Moreover, GLS demonstrated the highest diagnostic ability when compared with traditional CMR structural parameters and ECV to diagnose patients with HFpEF and obesity in the setting of obesity. Interpretation: Higher systemic inflammation, and worse GLS and eGLSR may be the distinct features of obesity-related HFpEF phenotype; strains and ECV may represent different mechanisms of HFpEF with obesity, deserving further study. Funding: The Construction Research Project of Key Laboratory (Cultivation) of Chinese Academy of Medical Sciences (2019PT310025); National Natural Science Foundation of China (81971588); Capital's Funds for Health Improvement and Research (CFH 2020-2-4034); Youth Key Program of High-level Hospital Clinical Research (2022-GSP-QZ-5).

IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma.

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, divergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8+ T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma.

Peptide Selection of MMP-1 for Electrochemical Sensing with Epitope-Imprinted Poly(TPARA-co-EDOT)s.

Instead of molecularly imprinting a whole protein molecule, imprinting protein epitopes is gaining popularity due to cost and solubility issues. Belonging to the matrix metalloproteinase protein family, MMP-1 is an interstitial collagenase that degrades collagen and may be involved in cell migration, cell proliferation, the pro-inflammatory effect, and cancer progression. Hence, it can serve as a disease protein biomarker and thus be useful in early diagnosis. Herein, epitopes of MMP-1 were identified by screening its crystal structure. To identify possible epitopes for imprinting, MMP-1 was cleaved in silico with trypsin, pepsin at pH = 1.3, and pepsin at pH > 2.0 using Peptide Cutter, generating peptide fragments containing 8 to 12 amino acids. Five criteria were applied to select the peptides most suitable as potential epitopes for MMP-1. The triphenylamine rhodanine-3-acetic acid (TPARA) functional monomer was synthesized to form a stable pre-polymerization complex with a selected template epitope. The complexed functional monomer was then copolymerized with 3,4-ethoxylenedioxythiophene (EDOT) using potentiodynamic electropolymerization onto indium−tin−oxide (ITO) electrodes. The composition of the molecularly imprinted poly(TPARA-co-EDOT) (MIP) was optimized by maximizing the film's electrical conductivity. Cyclic voltammetry was used to determine MMP-1 concentration in the presence of the Fe(CN)63−/Fe(CN)64− redox probe actuating the "gate effect." A calibration curve was constructed and used to determine the usable concentration range and the limit of detection as ca. 0.001 to 10.0 pg/mL and 0.2 fg/mL MMP-1, respectively. Finally, the MMP-1 concentration in the A549 human lung (carcinoma) culture medium was measured, and this determination accuracy was confirmed using an ELISA assay.

An advantageous application of molecularly imprinted polymers in food processing and quality control.

In the global market era, food product control is very challenging. It is impossible to track and control all production and delivery chains not only for regular customers but also for the State Sanitary Inspections. Certified laboratories currently use accurate food safety and quality inspection methods. However, these methods are very laborious and costly. The present review highlights the need to develop fast, robust, and cost-effective analytical assays to determine food contamination. Application of the molecularly imprinted polymers (MIPs) as selective recognition units for chemosensors' fabrication was herein explored. MIPs enable fast and inexpensive electrochemical and optical transduction, significantly improving detectability, sensitivity, and selectivity. MIPs compromise durability of synthetic materials with a high affinity to target analytes and selectivity of molecular recognition. Imprinted molecular cavities, present in MIPs structure, are complementary to the target analyte molecules in terms of size, shape, and location of recognizing sites. They perfectly mimic natural molecular recognition. The present review article critically covers MIPs' applications in selective assays for a wide range of food products. Moreover, numerous potential applications of MIPs in the food industry, including sample pretreatment before analysis, removal of contaminants, or extraction of high-value ingredients, are discussed.

Toward an effective occupational health and safety culture: A multiple stakeholder perspective.

INTRODUCTION: This paper uses an extensive review of the safety culture literature to identify three key themes (a) role of new employees, (b) absence of a pro-active approach, and (c) need for a 'No-blame' culture, and explores their impact on the occupational health and safety culture (OHS). METHOD: We use a qualitative study with a constructivist phenomenological approach consisting of 55 in-depth interviews with a diverse range of participants, including business owners, line managers and supervisors, OHS advisors, workers, and union representatives in Western Australia. A workplace vignette was used to elicit cultural norms derived from the participants' attitudes and beliefs, which were analyzed using NVivo software to conduct a thematic analysis to classify the interview text into specific concepts and phrases. RESULTS: Findings confirm the three themes identified from our literature review and provide useful insights into the challenges faced by the participants in the implementation of safety policies. PRACTICAL APPLICATIONS: Besides extending the occupational health and safety literature, these findings have important managerial implications in view of the evolving nature of work and workplaces.

Reliability of STOP-Bang questionnaire and pulse oximetry as predictors of OSA - a retrospective study.

OBJECTIVE: To verify the reliability of a STOP-Bang questionnaire and objective blood oxygen concentration (SpO2) estimation by pulse oximetry as an indicator of patients' vulnerability to OSA, by correlating data of these two tests with that of the "gold standard" all-night polysomnography. METHODS: STOP-Bang score and pulse oximetry value (SpO2) for each patient were tabulated against the total sleep AHI score (obtained from subsequent all-night polysomnography) and analyzed to evaluate the diagnostic accuracy of the STOP-Bang questionnaire and pulse oximetry. RESULTS: With sensitivity and specificity scores of 91.2% and 88.6%, respectively, positive predictive value 90.5%, negative predictive value 40.2%, the twin diagnostic test (STOP-Bang and pulse oximetry) was found to be highly congruent with the polysomnography (PSG), achieving a diagnostic accuracy of 85%. CONCLUSION: Dental chairside screening by STOP-Bang questionnaire and pulse oximetry would be a good option, especially where logistic and economic constraints impede all-night polysomnography.