The journal retracts the article titled "Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol Against Gram-Negative Bacterial Pathogens" [...].

Infantile haemangiomas (IH) are the most common vascular tumours of infancy, characterised by a predictable trajectory of rapid proliferation, plateau, and slow spontaneous involution. Although most regress uneventfully, a significant minority risk ulceration, functional compromise, or disfigurement, and therefore require timely intervention. The therapeutic landscape was once dominated by corticosteroids, interferon, and cytotoxic chemotherapeutics of modest efficacy and considerable toxicity. Management was revolutionized in 2008 by the discovery that the beta-blocker propranolol induced prompt and sustained regression. Propranolol has since become the established first-line therapy for IH, with efficacy and safety confirmed by randomized controlled trials and corroborated by observational cohorts. Mechanistically there are multiple temporally stratified actions: immediate vasoconstriction, suppression of angiogenic signalling pathways, induction of endothelial apoptosis, and ultimately the promotion of adipogenic differentiation in keeping with natural involution. Safety is favourable under expert supervision, though hypoglycemia remains the principal preventable hazard, necessitating caregiver education on feeding regimens and "sick day" rules. Rebound growth, encountered in roughly one-fifth of cases, usually responds to re-treatment. Alternative beta-blockers such as atenolol and nadolol provide comparable efficacy with potential advantages in tolerability or dosing convenience. Topical timolol has limited effectiveness for small superficial lesions, while sirolimus, becaplermin gel, laser devices, and surgery may have circumscribed adjunctive roles. Corticosteroids and cytotoxic agents are now confined to salvage use. Contemporary perspectives extend beyond pharmacology to encompass caregiver experience and health-system burden. Recent work highlights the low burden of treatment with propranolol, while digital innovations such as photo-triage during the COVID-19 pandemic illustrate opportunities to reduce healthcare exposure and improve equity of access. This review describes the evolution of drug therapy for IH and integrates mechanistic insights, clinical pragmatism, and patient-centred innovations to chart the current trajectory of care.

Coronavirus Disease2019 (COVID-19) can increase sympathetic nervous system activity by inducing systemic inflammation and a cytokine storm. This can result in elevated blood pressure, increased heart rate, and vasoconstriction. A 67-year-old Black male was admitted to the emergency department with a chief complaint of shortness of breath for 2 days. On examination, he exhibited edema and symmetric palpable pulses in his lower limbs. His electrocardiogram revealed left axis deviation, sinus tachycardia, and ST-segment elevation. Reverse transcription-polymerase chain reaction confirmed COVID-19. Hydralazine (5 mg) was administered intravenously immediately. The patient was re-evaluated after 20 min during his stay in the emergency department. After two 5 mg doses of hydralazine, he developed reflex tachycardia. To control heart rate, IV hydralazine was replaced with oral atenolol (50 mg once daily), a β1-blocker that reduces cardiac output. Subcutaneous enoxaparin 80 mg daily was given to prevent thrombotic complications in hospitalized COVID-19 patients. Acute hypertension and COVID-19-induced hypertensive emergencies in patients with preexisting hypertension are typically associated with a worse prognosis.

Wastewater-based epidemiology (WBE) is an approach that uses information obtained from the analysis of various metabolites or residues in wastewater with the aim of assessing the consumption of or exposure to chemicals or pathogens in a population connected to a sewage system. The aim of this work was to develop methods for the isolation and analysis of seven beta-blockers (acebutolol, atenolol, betaxolol, metoprolol, nadolol, pindolol and propranolol) in wastewater samples collected from the influent of the wastewater treatment plant in Cluj-Napoca, Romania, in order to estimate their consumption among the population in two time periods (February and October 2024) using WBE. The selected beta-blockers were extracted by solid phase extraction using a Strata C18-U cartridge and analyzed by liquid chromatography coupled with tandem mass spectrometry. The consumption was estimated using the daily mass load of pharmaceutical products reported per 1000 inhabitants (mg/day/1000inh) and varied in the following ranges: atenolol 0.03-3.74, nadolol 0.03-0.1, propranolol 0.04-0.72, betaxolol 0.07-0.38, and metoprolol 54.85-276.45. From the obtained results, it can be observed that metoprolol is the most used beta-blocker in the investigated population, followed by atenolol, propranolol and betaxolol. Other beta-blockers are consumed in small quantities or occasionally.

Water scarcity and water quality degradation have increased the interest in reclaimed water production from wastewater treatment plants. Among quality concerns, emerging contaminants (ECs) have gained attention due to their persistence and potential environmental and health risks. This study investigated the occurrence, spatial distribution, and removal of ECs in a full-scale Water Resource Recovery Facility (WRRF) operating an anaerobic-anoxic-aerobic process followed by membrane bioreactor (MBR) filtration in São Paulo State, Brazil. Wastewater samples were collected at different treatment stages, and surface waters from regional rivers were analyzed for comparison. Target compounds were determined by UPLC-MS/MS and GC-MS. All analytes were detected in raw sewage, with caffeine presenting the highest concentrations. High removal efficiencies were observed for paracetamol, caffeine, ibuprofen, naproxen, and atenolol (> 97%), while diclofenac and propranolol showed moderate removal (60-70%). Estrogenic compounds exhibited variable removal, and carbamazepine and its metabolites showed persistent behavior, with negative removal suggesting back-formation processes. The results confirm carbamazepine as a reliable chemical marker of treatment efficiency and indicate that, although reclaimed water showed high overall quality, complementary treatment may be required to meet stricter standards for emerging contaminants.

BackgroundHyperthyroidism is an immune-related adverse event associated with ICI use. Its underlying risk factors, progression to thyroiditis, and impact on patient outcomes remain less understood.MethodsData were obtained from the TriNetX network for patients aged ≥ 18 yr with cancers indicated for ICI therapy between January 1, 2013, and December 31, 2024. Patients with pre-existing thyroid disorders were excluded. Competing risk analyses evaluated hyperthyroidism or thyroiditis versus death within 12 months of ICI initiation. Cox proportional hazards modeling identified significant predictors, and backward elimination retained variables that met significance threshold.ResultsAmong 41,629 patients receiving ICIs, 2.2% developed hyperthyroidism and 1.6% developed thyroiditis within 12 months. In those with hyperthyroidism, 17% initiated metoprolol, 8.9% initiated propranolol, and 5.2% initiated atenolol. Mortality rate was 2.9%. Patients who developed hyperthyroidism were more likely to have RCC (p < 0.0001, SMD = 0.27) or endometrial cancer (p < 0.0001, SMD = 0.24) and less likely to have liver (p < 0.0001, SMD = 0.24) or bladder cancer (p < 0.0001, SMD = 0.1575). While Nivolumab and ipilimumab usage was more common in patients who developed hyperthyroidism, ipilimumab showed a higher hazard in CPH (HR: 1.39, p = 0.0001). Patients with type 1 diabetes also showed significantly higher risk (HR 1.70, p = 0.0362), while black or African American patients showed lower hazard (HR: 0.798, p = 0.0305).ConclusionICI-induced hyperthyroidism is associated with significant mortality. Identifying high-risk cancer subtypes and using beta-blockers for symptom control are essential to mitigating adverse effects.

Understanding the stability of biomarkers during sewer transport is one of the crucial steps when applying wastewater-based epidemiology (WBE) for assessing consumption or exposure to chemicals. Their stability could be impacted by chemical dosing, a common method used to control the generation of hydrogen sulfide in urban sewer networks. Nano zero valent iron (nZVI) has recently attracted attention due to its effectiveness on sulfide and methane removal. However, the impact of dosing nZVI on the transformation of biomarkers in sewers and the consequent influence on WBE estimation remains unknown. This study investigated the impact of nZVI dosage on adsorption and biotransformation processes of 20 pharmaceutical biomarkers in lab-scale sewer reactors. Dosing nZVI (50 mg Fe/L) effectively inhibited the production of sulfide and changed microbial communities in sewer biofilms. There was no adsorption observed when biomarkers interacted with nZVI only, indicating that adsorption to nZVI dosing was not the main mechanism for biomarker transformation. Meanwhile, the duration and amount of dosing nZVI had no impact on stable biomarkers with less 15% loss (e.g. cotinine, OH-cotinine, benzoylecgonine and acesulfame). In contrast, nZVI dosing affected the transformation of inherently moderately stable biomarkers like methamphetamine, 3,4-methylenedioxymethamphetamine, methylone, carbamazepine, ketamine and atenolol. These findings revealed the complex impacts of nZVI on mediating sewer conditions, biological compositions and in-sewer stability of biomarkers. An evaluation framework was applied to jointly consider the impact of nZVI dosing and hydraulic retention time on biomarker stability, which provides new knowledge for WBE's application in dynamic sewer systems.

This study presents, for the first time, the spatial and short-term temporal occurrence of forty-two multiclass pharmaceuticals, their metabolites, and personal care products in wastewater across a catchment area with and without rivers connected to wastewater treatment plants (WWTPs) in the eThekwini Metropolitan Municipality of South Africa. Four major WWTPs were studied, each with different wastewater treatment technologies and their receiving water bodies, over a week. This study compared the efficiency of the treatment plants and found that the removal efficiency depends on the treatment process employed. Wastewater treatment plants that employed activated sludge consistently achieve higher removal efficiencies for pharmaceuticals and personal care products (PPCPs) than plants that rely solely on screening and sedimentation. Most detected PPCPs increased downstream, indicating contributions from WWTP effluent; however, for some compounds, lower concentrations in the effluent relative to upstream concentrations led to dilution after mixing, demonstrating the combined influence of effluent inputs and hydrological mixing on river water quality. There is also concern about synergistic effects from the combination of these PPCPs, which may be detrimental despite their presence at trace levels. Among the PPCPs monitored, 26 were detected in the influent and effluent, with the most detected PPCPs in both being benzophenone-3, metformin, gliclazide, atenolol, carbamazepine, carbamazepine-10,11-epoxide, 10,11-dihydro-10-hydroxycarbamazepine, nicotine, caffeine, 1,7-dimethylxanthine, N-desmethyltramadol, and O-desmethyltramadol. The weekday-weekend concentrations of some PPCPs (citalopram, 1,7-dimethylxanthine, nicotine, metformin, atenolol, cimetidine, benzophenone-3, gliclazide, quetiapine, and 10,11-dihydro-10-hydroxycarbamazepine) were significantly different across the various plants, indicating variation in the consumption habits of the people these plants serve. The highest concentrations in the influents and effluents were observed for 1,7-dimethylxanthine (a metabolite of caffeine), with mean concentrations of 723 668.4 ± 180 002.5 ng L[-1] and 409 405.7 ± 173 761.3 ng L[-1], respectively. Except for acetaminophen, desvenlafaxine, carbamazepine-10,11-epoxide, nicotine, caffeine, and 1,7-dimethylxanthine in one or two treatment plants, the majority of the PPCPs in the effluent showed an insignificant to medium aquatic risk (this level of risk is similar for the studied surface water), based on an ecotoxicological risk assessment. Given that these PPCPs are present as complex mixtures with diverse physicochemical properties and varying capacities to influence a range of molecular and cellular processes in organisms, a better understanding of their ecological risk is needed to promote environmental health.

Sublingual drug delivery offers a non-invasive alternative to oral administration, allowing drugs to be rapidly absorbed while bypassing the first-pass effect. The purpose of this study was to compare the pharmacokinetics of model drugs following sublingual and oral administration in healthy human subjects and to explore the empirical relationship between sublingual drug-absorption parameters and the physicochemical properties of the model compounds. Orally disintegrating tablets and oral tablets of five model drugs atenolol, caffeine, naproxen, propranolol, and verapamil were administered to healthy human subjects via both sublingual and oral routes. Sublingual administration resulted in faster absorption (shorter Tmax) and higher Cmax and AUC for all drugs except naproxen. Sublingual absorption rate constants (Ka) were estimated via deconvolution using the Wagner-Nelson or Loo-Riegelman method, depending on drug kinetics. Multiple linear regression (MLR) identified molecular weight (MW), number of rotatable bonds (nRB), and LogD7.4 as empirically associated with 65% of the variability in Ka (R[2] = 0.65). The resulting model is expressed as the following equation: Ka = -4.05 + 0.04 x MW -0.70 x NRB - 0.89 x LogD7.4. Drugs with lower lipophilicity and molecular flexibility exhibited faster sublingual absorption. These findings help to highlight the important physicochemical properties that may influence sublingual absorption.

Freshwater river sediments are increasingly exposed to complex mixtures of anthropogenic contaminants, yet the ecological repercussions on indigenous microbial communities -the main drivers of biogeochemical cycling- remain poorly understood. Previous investigations have focused primarily on contaminant occurrence, with no integrated assessment linking sediment contamination to microbial community structure and function. The objective of this study is to characterize the microbiome of the Upper Litani River Basin and to determine how chronic inputs of pharmaceuticals and aromatic hydrocarbons influence taxonomic composition, diversity, and predicted metabolic functions. 54 sediment samples were collected across nine locations during consecutive wet and dry seasons. Target organic micropollutants were quantified in the river sediments using validated analytical methods, and spatiotemporal patterns in microbial composition and metabolic functional potential were determined using amplicon sequencing. Across all samples, 45 phyla were identified, with Pseudomonadota, Bacillota, and Actinomycetota consistently being the dominant taxa. At the genus level, microbial communities were dominated by Acinetobacter, Exiguobacterium, Proteiniclasticum, Planococcus, and Clostridium sensu stricto. Variations in microbial community structure were correlated with the occurrence and concentrations of specific organic micropollutants detected in the sediments, namely with the pharmaceuticals ibuprofen, clomipramine and atenolol, as well as the hydrocarbons o-xylene and toluene. Functional predictions revealed a microbiome highly oriented toward chemoheterotrophic metabolism, underscoring the community's response to persistent organic enrichment. Collectively, these results demonstrate that pollutant concentrations and chemical profiles act as a major ecological force that shapes sediment microbial community dynamics and metabolic function in impacted freshwater ecosystems.

Camizestrant, a next-generation selective estrogen receptor (ER) degrader and complete ER antagonist, has been associated with a reversible dose- and time-dependent heart rate (HR) reduction in clinical studies. This nonclinical investigation aimed to understand the mechanism of camizestrant-induced HR reduction. The effects of camizestrant on HR in vivo were assessed in rat and dog telemetry studies. Effects on pacemaker channel function in vitro were assessed using patch-clamp electrophysiology in Chinese hamster ovary cells expressing human hyperpolarization-activated cyclic nucleotide-gated channel 4 (hHCN4), human embryonic stem cell (hESC)-derived sinoatrial node (SAN) cardiomyocytes, and primary rat SAN cardiomyocytes. In dogs, 28-day repeat-dose camizestrant administration caused a reversible dose- and time-dependent HR reduction (maximum reduction of 53 beats per min [bpm] on Day 25 vs pre-study levels at 20 mg/kg). HR reduction was also noted in rats (maximum reduction 89 bpm vs vehicle [23%] on Day 5 of a 7-day study at 75 mg/kg). Responses to chronotropic stimuli (e.g., atropine and isoprenaline) were reduced in dogs treated with camizestrant. Camizestrant-induced HR reduction was still present following combined sympathetic (atenolol) and parasympathetic (atropine) inhibition in dogs, as well as vagotomy in rats. Camizestrant reduced hHCN4 current density in Chinese hamster ovary cells, as well as beat rate and "funny" pacemaker (If) current activity in hESC-derived SAN cardiomyocytes. Camizestrant at 75 mg/kg for 7 days significantly reduced If current activity versus vehicle in isolated SAN cardiomyocytes. These results support the hypothesis that camizestrant exerts a pharmacologic, reversible reduction in HR by decreasing SAN pacemaker current activity.

Lawsone methyl ether (LME), a plant-based naphthoquinone, exhibits remarkable antihyperlipidemic, antioxidant, and anti-inflammatory properties, suggesting its potential evaluation as an antihypertensive drug. Thereby, its antihypertensive effects were assessed via an in vivo invasive procedure, alongside in vitro and in silico investigations, revealing its possible cardiovascular mechanisms. Results revealed that intravenous administration of LME at 0.0001, 0.0003, 0.001, 0.003, and 0.01 mg/kg induced a significant fall (5-42 mmHg) in mean arterial pressure (MAP). This fall in MAP was observed in normotensive as well as hypertensive rats, pre-treated with atropine and Nω-nitro-L-arginine methyl ester (L-NAME), suggesting the association of muscarinic receptors linked to nitric oxide (NO) pathway. Moreover, LME-induced vasorelaxation in the isolated aortic rings was significantly (p < 0.001) reduced by denudation, atropine, or L-NAME pre-treatment. Nonetheless, LME completely reversed the phenylephrine (PE), high K[+] and angiotensin-II-induced contractions, causing a rightward shift in Ca[+2] concentration response curves, identical to that of verapamil. This vasorelaxant activity was substantially ameliorated by 4-aminopyridine. Aortic rings pre-incubated with LME suppressed the contractions induced by PE in Ca[+2]-free medium, indicating inhibitory effect on internal Ca[+2]-release. In isolated atrial strips, LME induced atenolol-sensitive negative inotropic and chronotropic effects. Molecular docking uncovered cardiovascular targets for LME including NO synthase, muscarinic receptors, voltage-dependent Ca[+2] channels, β-adrenergic receptors, K[+] channels, and angiotensin-converting enzyme, supporting its potential role as a multi-target antihypertensive agent. In conclusion, LME delivered promising antihypertensive and cardio-suppressive effects by reducing peripheral resistance via muscarinic receptor-linked NO release, Ca[+2] antagonism, inhibiting Ca[+2] efflux, and reducing cardiac output.

Concentrations of basic drugs are often overpredicted by physiologically based pharmacokinetic models at very early time points after intravenous dosing. An empirical shallow compartment in our recently published permeability- and perfusion-limited PermQ model improved the prediction of this observed early distribution. This study aimed to determine the impact of glycocalyx, a glycoprotein and glycolipid covering on membranes of red blood cells (RBCs) and endothelium, on the partitioning and distribution of basic drugs. Hyaluronidase (50 μg/mL), heparinase (5 U/mL), and neuraminidase (0.1 U/mL) were used to remove the glycocalyx from rat or human RBCs. Confocal microscopy was used to confirm glycocalyx disruption. RBC partitioning experiments were conducted to obtain partition coefficients (Kp) in RBCs and PBS buffer in the presence or absence of glycocalyx. Experimental Kp for metoprolol and atenolol were scaled with glycocalyx dimensions. The human PermQ model was used to simulate the concentration-time profiles, and results were compared with simulations with empirical Kp values. Confocal microscopy confirmed RBC glycocalyx modification via sialic acid removal. Significant differences were observed for metoprolol and atenolol Kp on human RBC glycocalyx disruption. Modeling suggests that experimental Kp scaled with glycocalyx dimensions, while underestimating empirical Kp estimates, required a similar scalar for both drugs. This underestimation may be due to various reasons, such as incomplete RBC glycocalyx disruption or the RBC glycocalyx being an inadequate surrogate for the endothelial glycocalyx. Our results support the hypothesis that glycocalyx partitioning may partially explain the early distribution of the basic drugs metoprolol and atenolol. SIGNIFICANCE STATEMENT: We explored whether basic drugs can partition into glycocalyx, as this partitioning may explain the observed early time point distribution profile of basic drugs. Erythrocyte glycocalyx was tested as a possible in vitro model for the endothelial cell glycocalyx. Results indicate that glycocalyx partitioning partially explains the observed data for atenolol and metoprolol in humans.