Site-Specific Self-Catalyzed DNA Depurination: A Biological Mechanism That Leads to Mutations and Creates Sequence Diversity.

Self-catalyzed DNA depurination is a sequence-specific physiological mechanism mediated by spontaneous extrusion of a stem-loop catalytic intermediate. Hydrolysis of the 5'G residue of the 5'GA/TGG loop and of the first 5'A residue of the 5'GAGA loop, together with particular first stem base pairs, specifies their hydrolysis without involving protein, cofactor, or cation. As such, this mechanism is the only known DNA catalytic activity exploited by nature. The consensus sequences for self-depurination of such G- and A-loop residues occur in all genomes examined across the phyla, averaging one site every 2,000-4,000 base pairs. Because apurinic sites are subject to error-prone repair, leading to substitution and short frameshift mutations, they are both a source of genome damage and a means for creating sequence diversity. Their marked overrepresentation in genomes, and largely unchanging density from the lowest to the highest organisms, indicate their selection over the course of evolution. The mutagenicity at such sites in many human genes is associated with loss of function of key proteins responsible for diverse diseases.

Exosomal circSTRBP from cancer cells facilitates gastric cancer progression via regulating miR-1294/miR-593-3p/E2F2 axis.

CircRNAs represent a new class of non-coding RNAs which show aberrant expression in diverse cancers, such as gastric cancer (GC). circSTRBP, for instance, is suggested to be overexpressed in GC cells and tissues. However, the biological role of circSTRBP in the progression of GC and the potential mechanisms have not been investigated. circSTRBP levels within GC cells and tissues were measured by RT-qPCR. The stability of circSTRBP was assessed by actinomycin D and Ribonuclease R treatment. Cell proliferation, migration, invasion and in vitro angiogenic abilities after circSTRBP knockdown were analysed through CCK-8 assay, transwell culture system and the tube formation assay. The interaction of circSTRBP with the predicted target microRNA (miRNA) was examined by RNA immunoprecipitation and luciferase reporter assays. Xenograft tumour model was established to evaluate the role of exosomal circSTRBP in the tumour formation of GC cells. circSTRBP was upregulated in GC cells and tissues, and there was an increased level of circSTRBP in GC-derived exosomes. circSTRBP in the exosomes enhanced GC cell growth and migration in vitro, which modulates E2F Transcription Factor 2 (E2F2) expression through targeting miR-1294 and miR-593-3p. Additionally, exosomal circSTRBP promoted the tumour growth of GC cells in the xenograft model. Exosomal circSTRBP is implicated in the progression of GC by modulating the activity of miR-1294/miR-593-3p/E2F2 axis.

Vascular tissue - boon or bane? How pathogens usurp long-distance transport in plants and the defence mechanisms deployed to counteract them.

Evolutionary emergence of specialised vascular tissues has enabled plants to coordinate their growth and adjust to unfavourable external conditions. Whilst holding a pivotal role in long-distance transport, both xylem and phloem can be encroached on by various biotic factors for systemic invasion and hijacking of nutrients. Therefore, a complete understanding of the strategies deployed by plants against such pathogens to restrict their entry and establishment within plant tissues, is of key importance for the future development of disease-tolerant crops. In this review, we aim to describe how microorganisms exploit the plant vascular system as a route for gaining access and control of different host tissues and metabolic pathways. Highlighting several biological examples, we detail the wide range of host responses triggered to prevent or hinder vascular colonisation and effectively minimise damage upon biotic invasions.

Immune checkpoint inhibitor-associated nephritis - treatment standard.

Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAE's) more frequently. Renal irAE's, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2-5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both CTLA-4 and PD1/PDL-1 blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs, and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management, and prognostication of ICI-AKI.

Modulating the Electronic Structures of Pt on Pt/TiO2 Catalyst for Boosting Toluene Oxidation.

Surface hydroxyl groups commonly exist on the catalyst and present a significant role in the catalytic reaction. Considering the lack of systematical researches on the effect of the surface hydroxyl group on reactant molecule activation, the PtOx/TiO2 and PtOx-y(OH)y/TiO2 catalysts were constructed and studied for a comprehensive understanding of the roles of the surface hydroxyl group in the oxidation of volatiles organic compounds. The PtOx/TiO2 formed by a simple treatment with nitric acid presented greatly enhanced activity for toluene oxidation in which the turnover frequency of toluene oxidation on PtOx/TiO2 was around 14 times as high as that on PtOx-y(OH)y/TiO2. Experimental and theoretical results indicated that adsorption/activation of toluene and reactivity of oxygen atom on the catalyst determined the toluene oxidation on the catalyst. The removal of surface hydroxyl groups on PtOx promoted strong electronic coupling of the Pt 5d orbital in PtOx and C 2p orbital in toluene, facilitating the electron transfers from toluene to PtOx and subsequently the adsorption/activation of toluene. Additionally, the weak Pt-O bond promoted the activation of surface lattice oxygen, accelerating the deep oxidation of activated toluene. This study clarifies the inhibiting effect of surface hydroxyl groups on PtOx in toluene oxidation, providing a further understanding of hydrocarbon oxidation.

Study of the excess mortality associated with the SARS-CoV-2 pandemic in the Local Health Authorities and Districts of the Autonomous Region of Sardinia - quinquennium 2017-2021.

Background: Based on the indications of the Italian National Recovery and Resilience Plan and the Ministerial Decree n°77/2022, detecting specific populations' social-welfare needs is essential to reorganize the national and regional health service. The present analysis studies the impact of pandemic and pre-pandemic conditions in terms of mortality on Sardinian health service organizational subunits to indirectly investigate the need for specific social and health interventions. Design: Retrospective observational mortality study on the Sardinian resident population, surveyed by the Italian National Institute of Statistics (Istat) from 2017 to 2021. Methods: The database was built by crossing demographic data from the Istat divided into 21 five-year age groups (0-4 to 100+). Mortality and excess mortality were calculated with a focus on local health authorities and districts. The analysis were made considering three age groups (0-64, ≥ 65, 0-100+) and comparing the individual years 2020 and 2021 with the pre-pandemic triennium 2017-2019. To better understand the phenomenon of excess mortality, the old age index was calculated for the Local Health Authority and District for each year of the quinquennium considered. Results: Standardized mortality ratios increased in the biennium of the SARS-CoV-2 pandemic compared to the baseline 2017-2019. A global increaseof the Standardized mortality ratios in all districts (2021) was measured, including those with Standardized mortality ratios already increasing in 2020. Notably, the Standardized mortality ratios (2020 and 2021) were often increased by the 0-64 age group. The regional excess mortality (0-100+) confirmed an increase in mortality compared to the baseline, with a slight decrease from 2020 to 2021. Conclusions: Sardinia presents peculiar demographic and geographical characteristics. Monitoring mortality rates and excess mortality confirms to be crucial to constantly re-modulating health interventions and planning of the supply of services, including the equitable allocation of resources based on actual health needs. Sardinia should embrace the concept of "age-friendly community" and create communities designed to promote active aging and social participation.

Topologically Tunable Conjugated Metal-Organic Frameworks for Modulating Conductivity and Chemiresistive Properties for NH3 Sensing.

Electrically conductive metal-organic frameworks (cMOFs) have garnered significant attention in materials science due to their potential applications in modern electrical devices. However, achieving effective modulation of their conductivity has proven to be a major challenge. In this study, we have successfully prepared cMOFs with high conductivity by incorporating electron-donating fused thiophen rings in the frameworks and extending their π-conjugated systems through ring-closing reactions. The conductivity of cMOFs can be precisely modulated ranging from 10-3 to 102 S m-1 by regulating their dimensions and topologies. Furthermore, leveraging the inherent tunable electrical properties based on topology, we successfully demonstrated the potential of these materials as chemiresistive gas sensors with an outstanding response toward 100 ppm NH3 at room temperature. This work not only provides valuable insights into the design of functional cMOFs with different topologies but also enriches the cMOF family with exceptional conductivity properties.

Modulating Hydrogen Adsorption by Unconventional p-d Orbital Hybridization over Porous High-entropy Alloy Metallene for Efficient Electrosynthesis of Nylon-6 Precursor.

Renewable electricity driven electrosynthesis of cyclohexanone oxime (C6H11NO) from cyclohexanone (C6H10O) and nitrogen oxide (NOx) is a promising alternative to traditional environment-unfriendly industrial technologies for green synthesis of C6H11NO. Precisely controlling the reaction pathway of the C6H10O/NOx-involved electrochemical reductive coupling reaction is crucial for selectively producing C6H11NO, which is yet still challenging. Herein, we report a porous high-entropy alloy PdCuAgBiIn metallene (HEA-PdCuAgBiInene) to boost the electrosynthesis of C6H11NO from C6H10O and nitrite, achieving a high Faradaic efficiency (47.6%) and almost 100% yield under ambient conditions. In situ Fourier transform infrared spectroscopy and theoretical calculations demonstrate that unconventional orbital hybridization between d-block metals and p-block metals could regulate the local electronic structure of active sites and induce electron localization of electron-rich Pd sites, which tunes the active hydrogen supply and facilitates the generation and enrichment of key intermediates NH2OH* and C6H10O*, and efficiently promotes their C-N coupling to selectively produce C6H11NO.

Facile Formation of Sulfurized Nanorod-Like ZnO/Zn(OH)2 and Hierarchical Flower-Like γ-Zn(OH)2 /ϵ-Zn(OH)2 from a Green Synthesis and Application as Luminescent Solar Concentrator.

This research endeavors to overcome the significant challenge of developing materials that simultaneously possess photostability and photosensitivity to UV-visible irradiation. Sulfurized nanorod (NR)-like ZnO/Zn(OH)2 and hierarchical flower-like γ-Zn(OH)2 /ϵ-Zn(OH)2 were identified from XRD diffraction patterns and Raman vibrational modes. The sulfurized material, observed by FEG-SEM and TEM, showed diameters ranging from 10 and 40 nm and lengths exceeding 200 nm. The S2- ions intercalated Zn2+ , modulating NRs to dumbbell-like microrods. SAED and HRTEM illustrated the atomic structure in (101) crystal plane. Its direct band gap of 3.0 eV was attributed to the oxygen vacancies, which also contribute to the deep-level emissions at 422 and 485 nm. BET indicated specific surface area of 4.4 m2 g-1 and pore size as mesoporosity, which are higher compared to the non-sulfurized analogue. These findings were consistent with the observed photocurrent, photostability and photoluminescence (PL), further supporting the suitability of sulfurized NR-like ZnO/Zn(OH)2 as a promising candidate for Luminescent solar concentrators (LSC)-photovoltaic (PV) system.

Sex-oriented perspectives in immunopharmacology.

Several immunopharmacological agents are effective in the treatment of cancer and immune-mediated conditions, with a favorable impact on life expectancy and clinical outcomes for a large number of patients. Nevertheless, response variation and undesirable effects of these drugs represent major issues, and overall efficacy remains unpredictable. Males and females show a distinct difference in immune system responses, with females generally mounting stronger responses to a variety of stimuli. Therefore, exploring sex differences in the efficacy and safety of immunopharmacological agents would strengthen the practice of precision medicine. As a pharmacological target highlight, programmed cell death 1 ligand 1 (PD-L1) is the first functionally characterized ligand of the coinhibitory programmed death receptor 1 (PD-1). The PD-L1/PD-1 crosstalk plays an important role in the immune response and is relevant in cancer, infectious and autoimmune disease. Sex differences in the response to immune checkpoint inhibitors are well documented, with male patients responding better than female patients. Similarly, higher efficacy of and adherence to tumor necrosis factor inhibitors in chronic inflammatory conditions including rheumatoid arthritis and Crohn's disease have been reported in male patients. The pharmacological basis of sex-specific responses to immune system modulating drugs is actively investigated in other settings such as stroke and type 1 diabetes. Advances in therapeutics targeting the endothelium could soon be wielded against autoimmunity and metabolic disorders. Based on the established sexual dimorphism in immune-related pathophysiology and disease presentation, sex-specific immunopharmacological protocols should be integrated into clinical guidelines.

Modulating effects of capsaicin on glucose homeostasis and the underlying mechanism.

Abnormal glucose homeostasis is linked to a variety of metabolic syndromes, such as insulin resistance, obesity, type-2 diabetes mellitus, hypertension and cardiovascular diseases. Maintenance of normal glucose homeostasis is important for the body to keep normal biological functions. As the major bioactive ingredient in chili peppers responsible for the pungent flavor, capsaicin has been reported to effectively improve glucose homeostasis with low cytotoxicity. In this review, the modulating effects of capsaicin on glucose homeostasis in cell models, animal models and human trials are summarized through both TRPV1 dependent and TRPV1 independent pathways. The relevant molecular mechanisms underlying its regulatory effects are also evaluated. Understanding the effects and mechanisms of capsaicin on glucose metabolism could provide theoretical evidence for its application in the food and pharmaceutical industries.

Use patterns of systemic immunomodulators in the United States before and after dupilumab approval in adults with atopic dermatitis.

PURPOSE: The patterns of dupilumab use, the first systemic drug approved for the treatment of atopic dermatitis (AD), is not well understood in the context of off-label systemic medications. OBJECTIVE: To describe patterns of prescribing, switching and discontinuing systemic AD drugs, before and after the approval of dupilumab and understand variables associated with dupilumab prescription. METHODS: Using longitudinal claims data, we identified patients with AD who initiated a systemic therapy (dupilumab, cyclosporine, methotrexate, azathioprine, mycophenolate) from March 2015 to February 2021, with a washout period of 1 year. We used Sankey plots to visualize longitudinal patterns of use at 3, 6, and 12 months and logistic regression to determine associates of dupilumab prescription. RESULTS: The number of patients starting systemic treatment increased from 319 before dupilumab approval to 1358 after. Dupilumab use increased from 72% to 84%. In 2019-2020, 36% of patients discontinued systemic treatment within a year compared to 62% in 2015-2016. 92% of patients who started dupilumab in 2020-2021 had received no other systemic treatment before. Patients <60 years and those who used steroid-sparing topical treatments were more likely to receive dupilumab. CONCLUSION: Among new users of a systemic treatment for AD, dupilumab was most used treatment by far.

Local drug delivery in the treatment of furcation defects in periodontitis: a systematic review.

OBJECTIVES: To evaluate the effect of subgingival administration of various antimicrobials and host-modulating agents in furcation defects as an adjunct to scaling and root planing (SRP) compared to SRP alone or combined with placebo. METHODS: A systematic review was carried out using MEDLINE-PubMed, Embase, and Scopus for articles up to October 2022 in addition to hand searches. All longitudinal studies that evaluated the effect of subgingival application of antimicrobial and host-modulating agents in furcation defects as adjuncts to SRP compared to SRP alone or SRP + placebo with at least 3 months of follow-up were eligible for inclusion. RESULTS: A total of eight studies were included. Superior clinical treatment outcomes were shown when alendronate, rosuvastatin, boric acid, simvastatin, and tetracycline (only at 3 months) were utilized in furcation defects in conjunction with SRP alone or SRP + placebo. Significant improvement was reported in radiographic bone defect depth and defect depth reduction when SRP was supplemented with alendronate, rosuvastatin, boric acid, and simvastatin. CONCLUSIONS: Within the limitations of this review, the adjunctive subgingival administration of medications and host-modulating agents in furcation defects may confer additional clinical and radiographic benefits than non-surgical periodontal treatment alone. Future investigations are needed to confirm their long-term effectiveness. CLINICAL RELEVANCE: Local host modulators and antimicrobials may be used supplementary to enhance the clinical and radiographic treatment outcomes of conventional periodontal therapy in furcation defects.

Nonlinear Robust Control by a Modulating-Function-Based Backstepping Super-Twisting Controller for a Quadruple Tank System.

In this paper, a robust nonlinear approach for control of liquid levels in a quadruple tank system (QTS) is developed based on the design of an integrator backstepping super-twisting controller, which implements a multivariable sliding surface, where the error trajectories converge to the origin at any operating point of the system. Since the backstepping algorithm is dependent on the derivatives of the state variables, and it is sensitive to measurement noise, integral transformations of the backstepping virtual controls are performed via the modulating functions technique, rendering the algorithm derivative-free and immune to noise. The simulations based on the dynamics of the QTS located at the Advanced Control Systems Laboratory of the Pontificia Universidad Católica del Perú (PUCP) showed a good performance of the designed controller and therefore the robustness of the proposed approach.

Investigation of the Effects of Monomeric and Dimeric Stilbenoids on Bacteria-Induced Cytokines and LPS-Induced ROS Formation in Bone Marrow-Derived Dendritic Cells.

Stilbenoids are anti-inflammatory and antioxidant compounds, with resveratrol being the most investigated molecule in this class. However, the actions of most other stilbenoids are much less studied. This study compares five monomeric (resveratrol, piceatannol, pterostilbene, pinostilbene, and trimethoxy-resveratrol) and two dimeric (dehydro-δ-viniferin and trans-δ-viniferin) stilbenoids for their capability to modulate the production of bacteria-induced cytokines (IL-12, IL-10, and TNF-α), as well as lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), in murine bone marrow-derived dendritic cells. All monomeric species showed dose-dependent inhibition of E. coli-induced IL-12 and TNF-α, whereas only resveratrol and piceatannol inhibited IL-10 production. All monomers, except trimethoxy-resveratrol, inhibited L. acidophilus-induced IL-12, IL-10, and TNF-α production. The dimer dehydro-δ-viniferin remarkably enhanced L. acidophilus-induced IL-12 production. The contrasting effect of resveratrol and dehydro-δ-viniferin on IL-12 production was due, at least in part, to a divergent inactivation of the mitogen-activated protein kinases by the two stilbenoids. Despite having moderate to high total antioxidant activity, dehydro-δ-viniferin was a weak inhibitor of LPS-induced ROS formation. Conversely, resveratrol and piceatannol potently inhibited LPS-induced ROS formation. Methylated monomers showed a decreased antioxidant capacity compared to resveratrol, also depending on the methylation site. In summary, the immune-modulating effect of the stilbenoids depends on both specific structural features of tested compounds and the stimulating bacteria.

Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Mapping caudal inferior parietal cortex supports the hypothesis about a modulating cortical area.

The cytoarchitectonically tripartite organization of the inferior parietal cortex (IPC) into the rostral, the middle and the caudal clusters has been generally ignored when associating different functions to this part of the cortex, resulting in inconsistencies about how IPC is understood. In this study, we investigated the patterns of functional connectivity of the caudal IPC in a task requiring cognitive control, using multiband EPI. This part of the cortex demonstrated functional connectivity patterns dissimilar to a cognitive control area and at the same time the caudal IPC showed negative functional associations with both task-related brain areas and the precuneus cortex, which is active during resting state. We found evidence suggesting that the traditional categorization of different brain areas into either task-related or resting state-related networks cannot accommodate the functions of the caudal IPC. This underlies the hypothesis about a new brain functional category as a modulating cortical area proposing that its involvement in task performance, in a modulating manner, is marked by deactivation in the patterns of functional associations with parts of the brain that are recognized to be involved in doing a task, proportionate to task difficulty; however, its patterns of functional connectivity in some other respects do not correspond to the resting state-related parts of the cortex.

Evolution-Based Protein Engineering for Antifungal Peptide Improvement.

Antimicrobial peptides (AMPs) have been considered as the alternatives to antibiotics because of their less susceptibility to microbial resistance. However, compared with conventional antibiotics they show relatively low activity and the consequent high cost and nonspecific cytotoxicity, hindering their clinical application. What's more, engineering of AMPs is a great challenge due to the inherent complexity in their sequence, structure, and function relationships. Here, we report an evolution-based strategy for improving the antifungal activity of a nematode-sourced defensin (Cremycin-5). This strategy utilizes a sequence-activity comparison between Cremycin-5 and its functionally diverged paralogs to identify sites associated with antifungal activity for screening of enhanceable activity-modulating sites for subsequent saturation mutagenesis. Using this strategy, we identified a site (Glu-15) whose mutations with nearly all other types of amino acids resulted in a universally enhanced activity against multiple fungal species, which is thereby defined as a Universally Enhanceable Activity-Modulating Site (UEAMS). Especially, Glu15Lys even exhibited >9-fold increased fungicidal potency against several clinical isolates of Candida albicans through inhibiting cytokinesis. This mutant showed high thermal and serum stability and quicker killing kinetics than clotrimazole without detectable hemolysis. Molecular dynamic simulations suggest that the mutations at the UEAMS likely limit the conformational flexibility of a distant functional residue via allostery, enabling a better peptide-fungus interaction. Further sequence, structural, and mutational analyses of the Cremycin-5 ortholog uncover an epistatic interaction between the UEAMS and another site that may constrain its evolution. Our work lights one new road to success of engineering AMP drug leads.

Dihydroeugenol derivatives associated with blue LED light: A different form to face multidrug resistant (MDR) bacteria.

Eugenol has already had its pharmacological properties elucidated in previous studies, including antibacterial and antifungal properties. Based on such information, this study aimed to evaluate the antibacterial and modulatory activity of coumarin compounds prepared from dihydroeugenol and to associate them with blue LED light for the same activity. For this study, five of the substances available: compound 1 (C1), 8-methoxy-2-oxo-6-propyl-2H-chromen-3-carboxylic acid, compound (C2), 3-(hydroxy(4-nitrophenyl)methyl)-8- methoxy-6-propyl-2H-chromen-2-one, compound 7 (C3), 8-hydroxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one, compound 8 (C4), 3-(4-aminobenzoyl)-8-methoxy-6-propyl-2H-chromen-2-one and Compound 9 (C5), 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one 2-one. To determine the MIC, the broth microdilution technique was used. The products were evaluated for their potential to modulate the activity of antibiotics. Afterward, the plates were submitted to blue LED light for 20 min. When exposed to LED, C3 exhibited a decrease in MIC for SA ATCC and C5 for EC ATCC, with an average of 645.08 µg/mL for both cases. C2 and C4 exhibited synergism in a greater number of situations. However, C3 showed promising activity against S. aureus. C1 and C2 already acted better against E. coli, with the difference that C1 acted better against these bacteria when associated with LED. In general, the compounds studied here exhibited good antibacterial activity when associated with LED.

Positive acetylcholine receptor antibody in nonmyasthenic patients.

INTRODUCTION/AIMS: In this study we aimed to determine the frequency of acetylcholine receptor (AChR) binding antibody positivity via neuroautoimmunity panel testing, and describe its occurrence in a group of nonmyasthenic disorders. METHODS: This is a retrospective analysis of patients who underwent neuroautoimmunity antibody panel testing from 2010 to 2018 at the Cleveland Clinic. RESULTS: A total of 10 855 patients received neuroautoimmunity antibody panel testing, and 224 (2.1%) patients were positive for AChR binding antibody. Fifty-eight patients with a known myasthenia gravis (MG) diagnosis and 11 patients with incomplete follow-up were excluded. Among the remaining 155 patients, 30 had newly diagnosed MG and 125 were nonmyasthenic. In 35 patients, MG was within the initial differential diagnosis based on the clinical presentation. In contrast to nonmyasthenic patients, myasthenic patients were more likely to have an initial clinical presentation raising suspicion for MG (73.3% vs 10.4%, P < .001), higher mean AChR binding antibody titer (8.2 ± 15.6 vs 0.4 ± 1.6 nmol/L, P = .011), and higher frequency of abnormal AChR modulating antibody (89.3% vs 23.9%, P < .001). A combination of AChR binding antibody of >0.5 nmol/L and modulating antibody of over 20% in patients with clinical suspicion of MG is virtually diagnostic of MG. A total of 31 (24.8%) nonmyasthenic patients carried coexisting autoimmune conditions. DISCUSSION: Elevated titers of AChR binding antibody can sometimes be found in nonmyasthenic patients. Combined analysis of clinical presentation, AChR binding antibody titer, and AChR-modulating antibody results can be helpful in confirming an MG diagnosis.