Search Results (2,383)

The global dissemination of multidrug-resistant (MDR) Salmonella through the international food trade poses a major One Health concern. We used whole-genome sequencing to characterize Salmonella isolates from poultry meat sold in Chile, including domestic and imported products from Brazil and Argentina. Sixty-one Salmonella isolates were recovered from poultry meat; S. Infantis predominated (59%), followed by S. Heidelberg. Among S. Heidelberg from imported-meat poultry, 92% carried the bla_CMY-2 gene, conferring resistance to β-lactams. Given the predominance of S. Infantis in poultry meat, we performed an additional in-depth genomic analysis of 73 S. Infantis isolates obtained from poultry meat (n = 32), surface water (n = 30), and human clinical cases (n = 11). Across sources, phenotypic resistance to ciprofloxacin and third-generation cephalosporins reached 93% and 70%, respectively, and MDR (≥3 antimicrobial classes) occurred in 71% of isolates, largely associated with bla_CTX-M-65 and gyrA mutations. The pESI (plasmid of emerging S. Infantis)-like plasmid, harboring antimicrobial resistance and virulence genes, appeared in 94% of isolates. Phylogenetic analyses showed close genetic relationships among food, environmental, and clinical isolates, suggesting potential transmission through contaminated poultry meat or water. These findings emphasize the emergence of MDR S. Infantis in Chile and underscore the need for integrated One Health surveillance and prudent antimicrobial use to mitigate foodborne AMR risks. Full article

Background/Objectives: Recent public and scientific discussions have raised concerns about a possible link between prenatal paracetamol exposure and autism spectrum disorder (ASD). However, pharmacovigilance-based evidence remains scarce, and the role of reporting bias has not been systematically assessed. This study aimed to characterize ASD-related adverse event reports involving paracetamol in the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) and to evaluate potential disproportionality signals, considering demographic, temporal, and geographic patterns. Methods: FAERS data from January 2010 to September 2025 were screened for reports listing paracetamol as the suspect drug and ASD-related Preferred Terms. After excluding duplicates and concomitant drugs, 1776 unique cases were analyzed. Patient demographics, reporter type, and country of origin were summarized descriptively. Disproportionality was calculated using four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM). Results: Among 172,129 paracetamol-associated reports, 1776 (1.03%) included ASD-related terms. All were classified as serious and mostly submitted by consumers (98.6%). Gender was available in 47.7% of cases, showing male predominance (68.8%). Most reports referred to fetal exposure during pregnancy. Nearly all originated from the United States (98.4%). A marked rise was observed after 2022, with 562 reports in 2023 and 1051 in 2025. Disproportionality analyses revealed consistently elevated signals (ROR = 69.8, PRR = 69.2, IC025 = 5.60, EB05 = 48.3). Conclusions: The strong disproportionality signal likely reflects increased public attention and reporting dynamics rather than a causal association. Further integration of pharmacovigilance and epidemiologic data is warranted to clarify the clinical significance of these findings. Full article

Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy. Full article

Suzetrigine was approved by the US American Food and Drug Administration in 2025 as the first oral, non-opioid, selective inhibitor of Na_V1.8 sodium channel for the treatment of acute pain. Therefore, it represents a groundbreaking advancement in pain management. This review aims to provide an overview of the milestones in the medicinal-chemical development of Na_V1.8 inhibitors, eventually leading to suzetrigine. The multi-step synthesis route of suzetrigine is presented. Taking structural features into account, insights are provided into what plays a role for the inhibition of the Na_V1.8 channel. In addition, pharmacodynamic and pharmacokinetic aspects of the new drug, such as bioavailability, metabolism, and interaction with CYP450 enzymes, are discussed. A summary based on a large number of clinical trials demonstrating remarkable efficacy completes this comprehensive drug profile of suzetrigine, while also addressing limitations of the clinical trials and suggesting future perspectives. Full article

Cosmetic wipes are made for multiple functions, baby care, hand washing, feminine and personal cleansing, removing makeup, and applying products such as deodorants and sunless tanners among other uses. Despite the presence of preservatives, cosmetic wipes can become contaminated during processing steps and usage, which may lead to skin infections and other health issues for consumers. No validated method exists for the microbiological testing of cosmetic wipes. The goal of this study was to develop and validate a specific sample preparation method for the quantitative detection of microorganisms in cosmetic wipes for inclusion in the FDA Biological Analytical Manual (BAM). Ten wipe types differing in their composition and preservative combinations were inoculated with Bacillus cereus spore suspensions at three concentration levels and aged for 14 days. Three extraction methods were compared: mBAM1g (reference method using 1 g samples), mBAMww (whole wipe method based on BAM Chapter 23), and ISOww (whole wipe method based on ISO method without Tween 80). For commercial wipes, mBAMww and ISOww, using whole wipes, performed similarly (p ≥ 0.05) or significantly better (p < 0.05) than mBAM1g. For laboratory-made wipes, 1 g samples showed higher recovery rates than whole wipes, likely due to cell loss during aging. Inoculation method and preservatives affect microbial distribution, survival, and recovery rates. T80 may have a positive effect on the recovery of B. cereus from wipes. This study recommends mBAMww for the microbiological analysis of cosmetic wipes. Full article

By analyzing Food and Drug Administration (FDA) enforcement reports from 2004 to 2025, we can determine the incidence of microbial contamination in non-sterile and sterile drugs in the United States of America and, at the same time, compare the trends and patterns over a period of 21 years to determine the distribution and frequency of microbial contaminants. The most common microorganisms detected from 2019 to 2025 were the mold Aspergillus penicilloides, with 17 citations for sterile products, followed by 16 citations for non-sterile products of Burkholderia cepacia complex (BCC) bacteria. Analysis from the last 21 years revealed the dominant microbial contaminants belong to the BCC, reaching a maximum level between 2012 and 2019. Some of the previous microbial contaminants, such as Salmonella and Clostridium, decline in the 2019–2025 period, with no notifications issued. S. aureus and Pseudomonas contamination persisted through the years but at very low levels. Gram-negative bacteria contaminated non-sterile drugs more frequently than Gram-positive. A worrisome trend continued with unacceptable levels of enforcement reports not providing any information on the identity of the microbial contaminant. New species of Bacillus and Acetobacter nitrogenifigens were responsible for a significant increase in non-sterile drug recalls. The main driver for sterile product recalls over a 21-year period is the lack of assurance of sterility (LAS) where major failures in process design, control, and operational execution were not conducive to the control of microbial proliferation and destruction. Enforcement data analysis identified the problematic trends and patterns regarding microbial contamination of drugs, providing important information to optimize process control and provide a framework for optimizing risk mitigation. Although the 21-year landscape demonstrated that some microbial contaminants have been successfully mitigated, others remain resilient. The emergence of new contaminants highlights the evolving nature of microbial risk. The consistent problem with LAS is not only a major regulatory violation but also a potential catalyst for the next major healthcare-associated outbreak. Full article

Explainability features are intended to provide insight into the internal mechanisms of an Artificial Intelligence (AI) device, but there is a lack of evaluation techniques for assessing the quality of provided explanations. We propose a framework to assess and report explainable AI features in medical images. Our evaluation framework for AI explainability is based on four criteria that relate to the particular needs in AI-enabled medical devices: (1) Consistency quantifies the variability of explanations to similar inputs; (2) plausibility estimates how close the explanation is to the ground truth; (3) fidelity assesses the alignment between the explanation and the model internal mechanisms; and (4) usefulness evaluates the impact on task performance of the explanation. Finally, we developed a scorecard for AI explainability methods in medical imaging that serves as a complete description and evaluation to accompany this type of device. We describe these four criteria and give examples on how they can be evaluated. As a case study, we use Ablation CAM and Eigen CAM to illustrate the evaluation of explanation heatmaps on the detection of breast lesions on synthetic mammographies. The first three criteria are evaluated for task-relevant scenarios. This framework establishes criteria through which the quality of explanations provided by medical devices can be quantified. Full article

Antiretroviral drugs are associated with increased body weight and metabolic disorders. Fat gain and insulin resistance are commonly associated with abdominal obesity in people with HIV (PWH). There is currently an open ongoing discussion about how antiretroviral therapy affects body weight and its significance in hunger–satiety circuit alteration. Until now, the impact of the drug on this circuit has not been explored. This study aimed to assess the hormones involved in appetite and satiety regulation in the serum and hypothalamus after efavirenz (EFV) administration in mice. EFV (10 mg/kg) and distilled water (1.5 μL/kg) (control group) were orally administered for 36 days to CD1 mice. Body weight and food intake were determined throughout treatment. At the end of the treatment, the metabolic profile (glucose, triglycerides, cholesterol) was assessed, and leptin, soluble receptor of leptin (sOB-R), and ghrelin were measured in serum; moreover, we evaluated the expression of growth hormone secretagogue receptor 1a (GHS-R1a), neuropeptide Y receptor 1 (NPYR1), and leptin in the hypothalamus, and a sucrose preference test (SPT) was conducted. Outcomes showed an increase in serum ghrelin and the expression of GHS-R1a and NPYR1 receptors in the hypothalamus, coinciding with an increase in appetite and preference for sucrose in mice in the EFV group. Furthermore, serum leptin, sOB-R, and the free leptin index (FLI) showed that hunger is not related to a lack of satiety. Despite increased food intake, a reduction in body weight was observed, and triglyceride and cholesterol levels were increased. According to our findings, mice treated with EFV showed a decrease in body weight, despite increased food intake resulting from appetite stimulation, which is caused by specific compounds, hormones, and neural signals acting on the brain’s hunger centres, primarily in the hypothalamus, promoting eating behaviours. However, further studies are necessary to investigate the mechanisms of EFV’s effects on energy expenditure. Full article

Diabetic wounds exhibit impaired immune function, delayed neutrophils recruitment, and heightened infection risk which compromises early infection control and delays healing. We have demonstrated that topical CCL3 treatment restores neutrophil influx, reduces bacterial infection by ~99%, and accelerates wound healing in diabetic mice. As per Food and Drug Administration (FDA) Guidelines for Investigational New Drug (IND), we conducted a 14-day acute toxicity study in diabetic mice following a single topical administration of CCL3 at effective low dose (1 µg) and high dose (10 µg) per wound. Mice were monitored for clinical signs, body weight, and food intake throughout the study period. On day 14, serum biochemistry (ALT, AST, BUN, creatinine, metabolic markers) and histopathology of major organs (liver, kidney, heart, lungs, spleen) were assessed. CCL3-treated diabetic mice exhibited no adverse clinical effects. Hematological and biochemical parameters remained within normal limits, and histopathological analyses revealed no additional organ injury in CCL3-treated groups compared to diabetic control mice. Intriguingly, CCL3-treated mice showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced serum IgG, indicating reduced systemic inflammation. Overall, our study demonstrates that diabetic mice tolerate topical CCL3 at doses up to 10 times the effective therapeutic concentration without evidence of systemic organ toxicity. These findings provide strong preclinical support for the translational development of CCL3 as a novel therapy for diabetic wound care. Full article

The mesenchymal–epithelial transition (MET) receptor is a tyrosine kinase activated by its sole known ligand, hepatocyte growth factor (HGF). MET signaling regulates key cellular processes, including proliferation, survival, migration, motility, and angiogenesis. Dysregulation and hyperactivation of this pathway are implicated in multiple malignancies, including lung, breast, colorectal, and gastrointestinal cancers. In non–small cell lung cancer (NSCLC), aberrant activation of the MET proto-oncogene contributes to 1% of known oncogenic drivers and is associated with poor clinical outcomes. Several mechanisms can induce MET hyperactivation, including MET gene amplification, transcriptional upregulation of MET or HGF, MET fusion genes, and MET exon 14 skipping mutations. Furthermore, MET pathway activation represents a frequent mechanism of acquired resistance to EGFR- and ALK-targeted tyrosine kinase inhibitors (TKIs) in EGFR- and ALK-driven NSCLCs. Although MET has long been recognized as a promising therapeutic target in NSCLC, the clinical efficacy of MET-targeted therapies has historically lagged behind that of EGFR and ALK inhibitors. Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. They have also demonstrated potential in overcoming MET-driven resistance to EGFR TKIs or ALK TKIs. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC. Full article

The landscape of oncologic therapies has undergone large changes since the introduction of monoclonal antibody (mAb) based immunotherapies in the late 1990s and early 2000s. MAb-based therapeutics, also called biologics or large molecules, have distinct pharmacological characteristics compared to chemotherapeutics and small molecules. Development of biologics requires thorough assessment of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics to ensure safety and demonstration of efficacy. This review provides an overview of the clinical pharmacology packages of biologics for the treatment of oncologic malignancies approved by the U.S. Food and Drug Administration (FDA) over the past decade (January 2015 and August 2025). The conduct of population PK (PopPK) and exposure-eesponse (E-R) analyses, as well as assessments for drug–drug interactions (DDIs), immunogenicity, and QT prolongation risk are discussed. The aim of this review is to provide insight into the clinical pharmacology assessments for approval of antibody-based therapies in oncology as well as provide a longitudinal view of clinical pharmacology packages in this space. Full article

Due to the complexity of blood glucose dynamics and the high variability of the physiological structure of diabetic patients, implementing a safe and effective insulin dosage control algorithm to keep the blood glucose of diabetic patients within the normal range (70–180 mg/dL) is currently a challenging task in the field of diabetes treatment. Deep reinforcement learning (DRL) has proven its potential in diabetes treatment in previous work, thanks to its strong advantages in solving complex dynamic and uncertain problems. It can address the challenges faced by traditional control algorithms, such as the need for patients to manually estimate carbohydrate intake before meals, the requirement to establish complex dynamic models, and the need for professional prior knowledge. However, reinforcement learning is essentially a highly exploratory trial-and-error learning strategy, which is contrary to the high-safety requirements of clinical practice. Therefore, achieving safer control has always been a major challenge for the clinical application of DRL. This paper addresses this challenge by combining the advantages of DRL and the traditional control algorithm—model predictive control (MPC). Specifically, by using the blood glucose and insulin data generated during the interaction between DRL and patients in the learning process to learn a blood glucose prediction model, the problem of MPC needing to establish a patient’s blood glucose dynamic model is solved. Then, MPC is used for forward-looking prediction and simulation of blood glucose, and a safety controller is introduced to avoid unsafe actions, thus restricting DRL control to a safer range. Experiments on the UVA/Padova glucose kinetics simulator approved by the US Food and Drug Administration (FDA) show that the time proportion of adult patients within the healthy blood glucose range under the control of the model proposed in this paper reaches 72.51%, an increase of 2.54% compared with the baseline model, and the proportion of severe hyperglycemia and hypoglycemia events is not increased, taking an important step towards the safe control of blood glucose. Full article

Lefamulin, a new, first-in-class pleuromutilin antibiotic, was recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of patients with community-acquired bacterial pneumonia (CABP). In this context, this review aimed to evaluate its activity against the most common pathogens causing this infection. A thorough search was performed in five databases (Embase, Scopus, Web of Science, PubMed, PubMed Central) from their inception to 14th of October 2025. Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints were applied. Out of a total of 224 articles identified, 11 were deemed eligible for inclusion. Resistance among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus isolates was 0–2.6%, 0–2.4%, and 0–4.3%, respectively. Even among isolates with specific mechanisms of resistance, such as β-lactamase-producing H. influenzae and methicillin-resistant S. aureus, resistance was below 2.4% and 3.4%, respectively. Among isolates for which no breakpoints were available (Moraxella catarrhalis, atypical pathogens, Enterococcus spp., Streptococcus spp., Haemophilus spp., and Staphylococcus spp.), MIC₉₀ values were low. An exception were isolates belonging to Enterococcus spp., which displayed MIC₉₀ values ranging from 0.25 to >16 mg/L in the two studies with relevant data. Lefamulin demonstrated broad in vitro activity against key pathogens causing CABP, making it a considerable addition to the therapeutic options for such infections, especially in cases where first-line agents cannot be used for reasons such as allergy or previous failure. Full article

Kombucha is a millennia-old beverage crafted from green or black tea and saccharides and fermented with a symbiotic culture of bacteria and yeast (SCOBY). This functional drink boasts health benefits, such as improved intestinal flora function, hepatoprotection and inhibition of amyloid fibers. It contains bioactive antioxidants, such as catechins, ascorbic acid, vitamins and other polyphenolic compounds. With kombucha’s rising popularity, the Food and Drug Administration (FDA) has implemented control procedures to ensure the quality and safety of this food product. Due to the antioxidant properties of the major bioactive compounds in kombucha, feasible and low-cost electroanalytical methods emerge as promising alternatives. The objective of this study was to evaluate the voltammetric behavior of kombucha samples to establish and compare their redox profiles and antioxidant activities. Thus, 18 kombucha samples were used, comprising commercial samples and samples prepared in the laboratory from different SCOBYs purchased from different countries, and analyzed by differential pulse voltammetry (DPV) and square wave voltammetry (SWV) on a carbon paste electrode (CPE). The electrochemical index (EI) values determined from the samples were used to establish their antioxidant activities. The EI values were also compared with spectrophotometric data from Folin–Ciocalteu (FC) and Ferric Reducing Antioxidant Power (FRAP) assays. Full article

Natamycin, a polyene macrolide antifungal, has long been used as a food preservative and is the only Food and Drug Administration (FDA)-approved topical treatment for fungal keratitis. While its safety is supported by specific ergosterol interaction and minimal systemic absorption, current research mainly focuses on short-term effects, often overlooking long-term, developmental, and microbiome-related impacts. In food applications, questions remain about cumulative exposure and potential disruptions to gut microbiota. For ophthalmology, advanced delivery methods like nanocarriers and hydrogels enhance drug penetration but may alter pharmacokinetics and pose formulation challenges. Regulatory approvals have historically depended on established safe use and limited toxicological data, emphasizing the need for more systematic evaluations. Zebrafish (Danio rerio) represent a promising yet underutilized model for addressing significant gaps in research, particularly in the realms of microbiome studies, ocular health, developmental processes, and multigenerational effects. When paired with omics technologies, zebrafish facilitate comprehensive system-level mapping of drug-induced outcomes. This review consolidates existing evidence and positions zebrafish as a vital translational link between in vitro assays, mammalian models, and clinical practice. Additionally, it proposes a framework to ensure the effective and scientifically supported use of natamycin in both food and medicinal applications. Full article