Search Results (178)

We report a unique pediatric acute myeloid leukemia (AML) case characterized by a CBFB::MYH11 fusion located on a supernumerary ring chromosome 16. Following diagnosis through comprehensive blood and bone marrow assays, the patient was enrolled in the Children’s Oncology Group (COG) study AAML1831 and randomized to the experimental treatment arm (Arm B). She received induction chemotherapy with CPX-351 (liposomal daunorubicin and cytarabine), gemtuzumab and ozogamicin (GO), and the cardioprotectant dexrazoxane and achieved complete remission (CR). The patient completed the treatment with sustained CR for 18 months. This case represents a rare cytogenetic phenomenon that is not well-documented in the current literature. Through a review of relevant publications, we contextualize this case within the spectrum of core binding factor AML (CBF-AML), highlighting diagnostic approaches, treatment strategies, and prognostic implications, particularly in cases involving atypical CBFB::MYH11 fusions. The durable remission observed in this patient, despite the unusual cytogenetic presentation, provides valuable insights into therapeutic management. This report underscores the cytogenetic and molecular heterogeneity of CBFB::MYH11 AML and emphasizes the importance of comprehensive genetic profiling using advanced techniques such as chromosomal microarray and next-generation sequencing. Full article

Adsorption studies of ciprofloxacine (CPX) and lidocaine (LID) emerging contaminants were performed on two fibrous Mg clays from the Madrid basin and Senegal. The samples were characterized by X-ray diffraction, ICP major element analysis, infrared spectroscopy, thermal analysis, optical petrography, scanning and transmission electron microscopy, cation exchange capacity (CEC), and N₂-BET analysis. Two mineral assemblages were established. Assemblage 1 mainly consists of sepiolite and minor trioctahedral smectite, while assemblage 2 is mostly composed of palygorskite, which is associated with dioctahedral smectite. The sorption was fast and reached equilibrium in 2 h. Fibrous Mg clays showed a higher adsorption capacity for CPX than for LID in the conditions studied. CPX adsorption on sepiolite and palygorskite can be the result of the combination of various mechanisms: ion exchange with permanently charged sites, electrostatic attractions with external surfaces, and an inner sphere complex with broken edges. LID adsorption mainly occurs by ion exchange and electrostatic interaction with the external surfaces of the clays. Dioctahedral smectite, as an associated phase, contributed to a higher removal percentage in palygorskite samples. By contrast, the trioctahedral smectite did not play a significant role in the adsorption of the samples with sepiolite. The mesoporous structure, high surface area, and moderate cation exchange of fibrous clays play a key role in the sorption process of CPX and LID. Full article

Background: Limited molecular surveillance continues to constrain Morocco’s HIV response, leaving subtype dynamics largely underreported. Once characterized by a predominance of subtype B, the Moroccan epidemic now appears to reflect shifting patterns shaped by regional and international connectivity. This study aimed to investigate HIV-1 molecular diversity, monitor circulating HIV-1 genetic variants, and inter-gene recombination in a cohort of people living with HIV in Morocco. Methods: We conducted an analysis of individuals diagnosed with HIV-1 infection or receiving follow-up care. Demographic and clinical data were extracted. Genotypic testing was performed on the protease/reverse transcriptase (PR/RT) and integrase (IN) regions of the pol gene using the HIV-1 Genotyping Kit with Integrase. Subtypes were assigned via Stanford HIVdb and HIV Blast, and phylogenetic relationships were analyzed using MEGA 12. Results: Of the 73 individuals enrolled, 64 were successfully sequenced. The median age was 43 years (IQR 35–51.3), with over half aged 25–44, and 85.9% were male. Heterosexual transmission was the main route (87.5%), and 59.4% were ART-naïve. Non-B subtypes predominated (87.5%), led by CRF02_AG (73.4%), followed by B (12.5%), C (7.8%), and A3 (3.1%). The cohort showed significant genetic diversity, including multiple CRFs such as CRF45_cpx (1.6%), CRF01_AE (1.6%), B/CRF02_AG (7.8%), G/CRF02_AG (3.1%), C/CRF02_AG (1.6%), CRF02_AG/CRF45_cpx (1.6%) and CRF02_AG/CRF22_01A1 (1.6%). Conclusions: This study provides updated insight into HIV-1 diversity in Morocco, showing a predominance of non-B subtypes, particularly CRF02_AG, and signals of increasing heterogeneity compared with reports from more than a decade ago that described subtype B predominance. These findings suggest a viral transition shaped in part by regional connectivity and highlight a gap in Morocco’s HIV strategy, underscoring the need to implement nationwide molecular surveillance to inform future HIV control efforts. Full article

Background/Objectives: Cardiorespiratory fitness (CRF) represents a strong and consistent predictor of mortality among adults. It is ideally expressed as the maximum or peak rate of oxygen consumption per kilogram of body mass (VO_2max) determined by the cardiopulmonary exercise test (CPX). Variance in CRF is mainly attributable to genetics and physical training; nevertheless, strong behavioral and socioeconomic confounders need to be considered. Among those, psychosocial stress may play an important role. Some papers show an association between low CRF and chronic stress conditions; nevertheless, CRF is generally estimated by indirect assessment and not directly measured by CPX. Methods: CRF was directly assessed by performing a CPX in 145 consecutive subjects (56 male, 89 female) (age 19–65 years) who attended our Exercise Medicine unit for health check-ups. Weekly total volume of physical activity (PA) was evaluated using a validated questionnaire (IPAQ); perceptions of stress, fatigue, and somatic symptoms were assessed using a self-administered questionnaire. Results: VO_2max was negatively correlated with perception of stress (p = 0.03), fatigue (p < 0.001), and somatic symptoms (p < 0.001); as expected, it was positively correlated with the weekly volume of PA (p < 0.001). This link was further evidenced by the observation that subjects who did not meet the PA goals as indicated by WHO guidelines presented a higher perception of stress, fatigue, and symptoms, as compared to physically active subjects. Conclusions: This direct link might, on the one hand, corroborate the role of exercise as a tool to manage stress and, on the other hand, focus on the role of stress as a possible determinant of CRF. Full article

Background: Taekwondo (TKD) and Tai Chi (TC) are promising interventions for enhancing health and physical function in older people, yet few studies have compared their effects across multiple domains. This study aimed to compare the effects of TKD versus TC on health status in independent older women. Methods: A randomized controlled trial was conducted with two parallel groups: TKD (n = 11) and TC (n = 10). Both groups trained three times per week for 8 weeks. Pre- and post-intervention assessments included anthropometry, submaximal CPX, 2-min step test, Timed Up-and-Go (TUG), isometric mid-thigh pull (IMTP), maximal isometric handgrip strength (MIHS), 30 s chair stand, 30 s arm curl, sit-and-reach, and back scratch. Results: Compared with TC, the TKD group showed significantly greater improvements in several cardiorespiratory outcomes, including VO₂ at VT1 and VT2, power output, VO₂/HR, OUES, and VE/VCO₂ slope (p < 0.05 to p < 0.001; d = 0.69–1.29). TKD participants also exhibited superior gains in maximal and relative IMTP, MIHS, relative MIHS, 30 s arm curl repetitions, and TUG performance (p < 0.05 to p < 0.001; d = 0.61–1.26). Both groups improved similarly in the 30 s chair stand test (p < 0.05). Flexibility outcomes diverged, with TKD improving sit-and-reach and TC showing greater gains in the back scratch test (p < 0.05). Conclusions: TKD was more effective than TC in improving cardiorespiratory fitness, muscle strength, and balance in older women and may represent a valuable health-oriented training strategy for this population. Full article

Background/Objective: The rise of multidrug-resistant bacteria underscores the urgent need for alternative antimicrobial strategies. Metal-based compounds and bacteriophage (phage) therapy have emerged as promising candidates, but the evolutionary trade-offs associated with these selective pressures and their combination remain poorly understood. This study aimed to investigate how prior exposure to T4 phage influences Escherichia coli B’s subsequent adaptation to iron (III) stress and to assess the resulting phenotypic and genomic signatures of dual resistance. Method: In this study, we performed experimental evolution using Escherichia coli B to investigate adaptive responses under four conditions: control (LB broth), T4 phage-only, iron (III) sulfate-only, and sequential phage followed by iron (III) exposure. Each treatment consisted of ten independently evolved populations (biological replicates), all derived from a common ancestral strain and passaged daily for 35 days. Phage resistance evolved rapidly, with complete resistance observed within 24 h of exposure. Results: In contrast, iron-selected populations evolved tolerance to high iron concentrations (1000–1750 mg/L) over time at a cost to resistance in other metals (gallium and iron (II) and antibiotics (tetracycline). Notably, prior phage exposure altered these outcomes: phage/iron-selected populations retained phage resistance and iron tolerance but showed diminished resistance to iron (II) and distinct antibiotic sensitivity profiles. Whole-genome sequencing revealed stressor-specific adaptations: large deletions in phage receptor-related genes (waaA and waaG) under phage pressure, and selective sweeps in iron-adapted populations affecting regulatory and membrane-associated genes (qseB, basR, aroK, fieF, rseB, and cpxP). Conclusions: These results demonstrate that the sequence of environmental stressors significantly shapes phenotypic and genetic resistance outcomes. Our findings highlight the importance of fitness epistasis and historical contingency in microbial adaptation, with implications for the design of evolution-informed combination therapies. Full article

Ciclopirox (CPX), a topical antifungal agent of the N-hydroxypyridone class, has gained renewed interest for its potential anticancer, antiviral, antibacterial, and neuroprotective effects. However, due to lack of reliable validated bioanalytical methods, current insights into its pharmacokinetics profile beyond topical use remain limited. To support therapeutic repurposing, we developed and validated a rapid, sensitive LC-MS/MS method for systemic pharmacokinetic evaluation in mice. The method employs methyl derivatization of CPX’s N-hydroxy group, producing methylated CPX (Me-CPX) for improved chromatographic performance which was subsequently retained on the Atlantis^TM T3 C18 reverse phase column. Concentration of CPX is determined indirectly based on the measured response of Me-CPX. The method achieved excellent recovery, a 4-min rapid runtime, sensitivity with LLOQ of 3.906 nM (0.81 ng/mL), and a linear range up to 1000 nM (r ≥ 0.9998). All validation parameters including intra- and inter-day accuracy, precision, matrix effects, stability and dilution integrity met the criteria defined by regulatory International Council for Harmonisation (ICH) M10 bioanalytical method validation guidelines. Application of the method to in vitro plasma protein binding studies revealed high protein binding (>99%) of CPX in both human and mice plasma. Preliminary PK analysis following intravenous and oral administration in CD-1 mice demonstrated moderate systemic exposure after oral dosing, with an estimated absolute bioavailability of 52.5%. These findings establish the method’s suitability and robustness for preclinical and future clinical development of CPX as a repurposed therapeutic agent. Full article

Traffic-induced noise pollution is a significant environmental issue, driving the development of advanced noise-reducing pavement materials. Semi-dense graded asphalt mixtures (SDAMs) present a promising compromise, offering enhanced acoustic properties compared to conventional dense-graded asphalt mixtures while maintaining superior durability to porous asphalt mixtures. However, the mechanism underlying the relationship between the energy dissipation characteristics and noise reduction effects of such mixtures remains unclear, which limits further optimization of their noise reduction performance. This study designed and prepared semi-dense graded noise-reducing asphalt mixtures SMA-6 TM, SMA-10 TM, and SMA-13 TM (SMA TM represents noise-reducing SMA mixture) based on traditional dense-graded asphalt mixtures SMA-6, SMA-10, and SMA-13, and conducted tests for water stability, high-temperature performance (60 °C), and low-temperature performance (−10 °C). Subsequently, energy loss parameters such as loss factor and damping ratio were calculated through dynamic modulus tests to characterize their energy dissipation properties. The mechanism linking the energy dissipation characteristics of semi-dense graded asphalt mixtures to noise reduction was investigated. Finally, the noise reduction effect was further verified through a tire free fall test and a close-proximity (CPX) method. The indoor test results indicate that the semi-dense mixtures exhibited a trade-off in performance: their dynamic stability was 11.1–11.3% lower and low-temperature performance decreased by 4.2% (SMA-13 TM) to 14.1% (SMA-6 TM), with moisture stability remaining comparable. Conversely, they demonstrated superior damping, with consistently higher loss factors and damping ratios. All mixtures reached peak damping at 20 °C, and the loss factor showed a strong positive correlation (R² > 0.91) with energy dissipation. Field results from a test section showed that the optimized SMA-10 TM mixture yielded a significant tire–road noise reduction of 3–5 dB(A) relative to the SMA-13, while concurrently meeting key performance criteria for anti-water ability and durability. This study establishes a link between the energy dissipation in SDAM and their noise reduction efficacy. The findings provide a theoretical framework for optimizing mixture designs and support the wider application of SDAM as a practical noise mitigation solution. Full article

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal proliferation of myeloid precursors and rapid progression. Historically consisting of intensive chemotherapy, AML management has evolved significantly due to advances in molecular diagnostics and risk stratification. This review discusses current therapeutic paradigms in AML, emphasizing the growing role of personalized medicine across age and risk groups. For younger, fit patients, intensive regimens such as the “7 + 3” protocol remain the standard, often enhanced by targeted agents like FMS-like tyrosine kinase 3 (FLT3) and IDH inhibitors. Older or unfit individuals benefit from low-intensity treatments such as hypomethylating agents combined with venetoclax, now considered a frontline standard of care. The use of liposomal chemotherapy (CPX-351), measurable residual disease (MRD) monitoring, and maintenance therapy further refine post-remission strategies. Emerging therapies, including menin inhibitors, antibody–drug conjugates, and immunotherapies like CAR-T cells and vaccines, offer additional options, especially in relapsed/refractory settings. This comprehensive review outlines the current landscape and future directions in AML therapy, emphasizing the transition toward individualized, mutation-driven treatment strategies. Full article

Background/Objectives: Fluoroquinolones (FQs) are broad-spectrum antibiotics associated with a constellation of severe, long-lasting adverse effects termed Fluoroquinolone-Associated Disability (FQAD), which often includes neuropsychiatric and gastrointestinal (GI) symptoms. Despite patient reports, GI dysfunction is not formally recognized within FQAD. This study aimed to establish a rodent model to investigate whether ciprofloxacin (CPX), the most commonly prescribed FQ, exposure induced long-lasting anxiety-like behavior and/or GI motility alterations. Methods: To test our hypothesis, Sprague Dawley rats were orally administered 20 mg/kg CPX, amoxicillin (AMX, antibiotic control), or saline (CTL) daily for 14 days. Anxiety-like behaviors were assessed weekly for 4 weeks post-treatment using the Elevated Plus-Maze, Marble Burying, and Open Field tests. GI transit was measured 2 weeks post-treatment via phenol red dye recovery analysis from the stomach and portions of the small intestine. Results: Our results demonstrated that CPX induced a transient, mild anxiety-like phenotype in rats, with behavioral changes largely resolving by week 4, becoming statistically indistinguishable from the CTL group. In contrast, CPX significantly accelerated GI transit, similar to the known prokinetic AMX, as evidenced by increased fractional dye recovery in the stomach and distal small intestine. This accelerated GI motility persisted weeks after CPX discontinuation. Conclusions: These findings establish a putative rodent model for FQAD, providing evidence that even small doses of CPX can induce acute, transient neuropsychiatric effects and, critically, persistent GI dysmotility. This supports the inclusion of GI dysfunction in FQAD symptomatology and highlights the need for judicious FQs prescription and comprehensive patient monitoring. Full article

Functional hydrogels have significant potential for applications in the pharmaceutical, agricultural, and environmental sectors. This study focuses on the synthesis of polyampholytic hydrogels through free radical polymerization using functionalized chitosans. The chitosan was modified with mono and disulfonic groups at different temperatures (25 °C and 60 °C) and reaction times (1, 8, 24 h), followed by further modification with glycidyl methacrylate to introduce vinyl groups into the polymers structure. The modified polymers were analyzed using proton nuclear magnetic resonance, Fourier transform infrared, scanning electron spectroscopy, thermogravimetric analysis, and solubility tests. Specifically, 0.74 mmol/g and 1.58 mmol/g of the primary amine groups available in the chitosan chain (out of a total of 4.93 mmol/g) were substituted with mono- and disulfonic groups, respectively. Following treatment with glycidyl methacrylate, 3.39 mmol/g and 2.21 mmol/g of the remaining primary amine groups in the mono- and disulfonic polymers, respectively, were substituted. The hydrogels obtained by the modified polymers at optimal conditions of 1 h and 25 °C, were characterized by the techniques already mentioned in addition to rheological tests, and water absorption studies across different pHs. The hydrogels demonstrated potential for environmental remediation, particularly in adsorptions of ciprofloxacin (CPX) and copper (Cu²⁺) from aqueous solutions at pH 7, achieving adsorption efficiencies of 24–25% for CPX and 83% for Cu²⁺. The results suggest that the synthesized hydrogels could provide an eco-friendly and efficient solution to challenges in wastewater treatment. Full article

Cyclophosphamide (CPX) is an alkylating agent commonly used for various hematological and solid malignancies. In addition to its use as a cytotoxic agent to directly kill tumor cells, numerous immunomodulatory properties of CPX in the tumor microenvironment (TME) of several cancer types have also been documented. These properties include the selective depletion of immune-suppressive regulatory T cells (Tregs), triggering of immunogenic cell death (ICD) and enhanced antigen presentation, and release of type I interferons (IFNs). Moreover, preclinical models as well as human clinical trials have investigated the efficacy of the low-dose “metronomic” scheduling of CPX in combination with immunotherapies such as immune checkpoint inhibitors, dendritic cell tumor vaccines, and tumor antigen peptide vaccines. The metronomic dosing schedule involves administering a continuous (or frequent, such as daily) low dose of chemotherapy rather than using the canonical approach of administering the maximum tolerated dose. Despite the approval of immune checkpoint inhibitors for clinical usage against an increasing number of cancers, many malignancies simply do not respond to checkpoint inhibition, in part due to the heterogeneous intratumoral network of immune-suppressive cell populations. The immunomodulatory effects of cyclophosphamide have strong translational applicability and could serve to enhance and bolster anti-tumor immunity, potentially synergizing with immune checkpoint inhibitors and other existing immunotherapy agents. Full article

Introduction: Genetic plasticity and adaptive camouflage in critical pathogens have contributed to the global surge in multidrug-resistant (MDR) infections, posing a serious threat to public health and therapeutic efficacy. Antimicrobial resistance, now a leading cause of global mortality, demands urgent action through diagnostics, vaccines, and therapeutics. In India, the Indian Council of Medical Research’s surveillance network identifies Escherichia coli as a major cause of urinary tract infections, with increasing prevalence in human gut microbiomes, highlighting its significance across One Health domains. Methods: Whole-genome sequencing of E. coli strain ECG015, isolated from a human gut sample, was performed using the Illumina NextSeq platform. Results: Genomic analysis revealed multiple antibiotic resistance genes, virulence factors, and efflux pump components. Phylogenomic comparisons showed close relatedness to pathovars from both human and animal origins. Notably the genome encoded protein tyrosine kinases (Etk/Ptk and Wzc) and displayed variations in the envelope stress-responsive CpxAR two-component system. Promoter analysis identified putative CpxR-binding sites upstream of genes involved in resistance, efflux, protein kinases, and the MazEF toxin–antitoxin module, suggesting a potential regulatory role of CpxAR in stress response and persistence. Conclusions: This study presents a comprehensive genomic profile of E. coli ECG015, a gut-derived isolate exhibiting clinically significant resistance traits. For the first time, it implicates the CpxAR two-component system as a potential central regulator coordinating antimicrobial resistance, stress kinase signaling, and programmed cell death. These findings lay the groundwork for future functional studies aimed at targeting stress-response pathways as novel intervention strategies against antimicrobial resistance. Full article

An electrochemical aptasensor was developed for the rapid and sensitive detection of ciprofloxacin (CPX) in milk samples. The device was fabricated on a polyethylene terephthalate (PET) substrate using a screen-printing technique with carbon-based conductive ink. Gold nanoparticles (AuNPs) were incorporated to enhance aptamer immobilization and facilitate electron transfer at the electrode surface. The sensor’s analytical performance was optimized by adjusting key parameters, including AuNP volume, DNA aptamer concentration, and incubation times for both the aptamer and the blocking agent (6-mercapto-1-hexanol, MCH). Differential pulse voltammetry (DPV) measurements demonstrated a linear response ranging from 10 to 50 nmol L⁻¹ and a low detection limit of 3.0 nmol L⁻¹. When applied to real milk samples, the method achieved high recovery rates (101.4–106.7%) with a relative standard deviation below 3.1%, confirming its robustness. This disposable and cost-effective aptasensor represents a promising tool for food safety monitoring, with potential for adaptation to detect other pharmaceutical residues in dairy products. Full article

In the absence of fully effective therapies and preventive strategies against the development of urosepsis, a deeper understanding of the virulence mechanisms of Uropathogenic Escherichia coli (UPEC) strains is needed. UPEC strains employ a wide range of virulence factors (VFs) to persist in the urinary tract and bloodstream. UPEC strains were isolated from patients with sepsis and a control group without sepsis. PCR was used to detect 36 genes encoding various groups of virulence and fitness factors. Profiling of both intracellular and extracellular bacterial proteins was also included in our approach. Bacterial metabolites were identified and quantified using GC-MS and LC-MS techniques. The UpaG autotransporter, a trimeric E. coli AT adhesin, was significantly more prevalent in urosepsis strains (p = 0.00001). Iron uptake via aerobactin and the Iha protein also appeared to be predictive of urosepsis (p = 0.03 and p = 0.002, respectively). While some studies suggest an association between S fimbriae and the risk of urosepsis, we observed no such correlation (p = 0.0001). Proteomic and metabolomic analyses indicated that elevated levels of bacterial citrate, malate, coenzyme Q10, pectinesterase (YbhC), and glutamate transport proteins, as well as the regulators PhoP two-component system, CpxR two-component system, Nitrate/nitrite response regulator protein NarL, and the Ferrienterobactin receptor FepA, may play a role in sepsis. These genetic biomarkers, proteins, and metabolites derived from UPEC could potentially serve as indicators for assessing the risk of developing sepsis. Full article