Search Results (304)

Background/Objectives: Malassezia pachydermatis is a lipophilic yeast frequently associated with otitis externa and dermatological disorders in companion animals. This study aimed to evaluate the antifungal susceptibility of M. pachydermatis isolates from dogs and cats and to investigate the genomic determinants of reduced susceptibility. Methods: Susceptibility testing of 87 clinical isolates was performed using a modified CLSI broth microdilution method in Sabouraud dextrose broth supplemented with 1% Tween 80. The whole genome of ten representative isolates was sequenced and the genetic factors that are involved in drug resistance were investigated. Results: Ketoconazole, itraconazole, and terbinafine exhibited the highest efficacy, while miconazole and clotrimazole showed reduced activity. Whole genome sequencing revealed single nucleotide polymorphisms (SNPs) in genes that play a key role in the ergosterol biosynthesis pathway, particularly in ERG11 and ERG1. While some specific amino acid substitutions (e.g., K446R in ERG11) were found only in isolates with elevated MIC values, no direct correlation with resistance could be unequivocally established. Conclusions: Genomic analyses also uncovered chromosomal mutations and the heterozygosity of certain isolates, suggesting that complex, multifactorial mechanisms may drive the development of drug resistance. These findings highlight the importance of standardized susceptibility testing and further genomic investigations to promote effective antifungal therapy in veterinary medicine. Full article

Staphylococcal bacterial biofilm plays an important role in the pathogenesis and bacterial persistence of chronic rhinosinusitis. N-acetyl cysteine (NAC) has an inhibitory role in biofilm formation, suppressing adhesion and matrix production or favoring dispersal of preformed biofilm. The aim of this study was to examine the in vitro effect of NAC on Staphylococcal biofilm formation by bacterial strains isolated from tissue samples of patients with chronic rhinosinusitis with or without nasal polyps (CRSwNP and CRSsNP). Prospective study included 75 patients with CRS. The biofilm-forming capacity of isolated strains was detected by microtiter-plate method and the effects of sub-inhibitory (1/2x, 1/4x, and 1/8x minimal inhibitory concentration, MIC) and supra-inhibitory minimal concentrations (2x, 4x, and 8xMIC) of NAC on biofilm production were investigated. Staphylococcal bacterial strains were isolated in 54 (72%) patients, and the most frequently isolated species were Staphylococcus aureus (40.7%). Coagulase-negative Staphylococci species were weak producers of biofilm, while S. aureus was a strong biofilm producer. Concentration of 3.1 mg/mL (1/2 MIC) was sufficient to completely prevent biofilm formation in 77.8% of the isolates, where 49.6 mg/mL (8xMIC) led to the complete eradication of formed biofilm in 81.5% of the isolates. The subinhibitory and eradication effects were dose- and strain-dependent. There were no significant differences in MIC values between isolates from patients with CRSwNP and CRSsNP isolates. NAC proved to be effective in inhibiting biofilm formation and reducing formed biofilm by Staphylococcal isolates from patients with CRS. A comparable antibiofilm effect was exhibited in both phenotypes of CRS, indicating that NAC’s antibiofilm activity was independent of the underlying clinical phenotype, and more targeted on biofilm matrix components. Full article

The objective of this study is to evaluate, for the first time, the chemical composition and the antioxidant, enzyme inhibitory, photoprotective and antibacterial properties of the Tamarix boveana essential oil (EO) as well as its organic extracts. The analysis of the EO obtained from the aerial parts of T. boveana was carried out employing the technique of gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC-MS). Forty-four constituents were identified, constituting 91.18% of the oil, with the major compounds being γ-cadinene (9.41%), β-caryophyllene (6.71%), limonene (6.5%), p-cymene (6.16%), copaene (4.37%), terpinen-4-ol (4.23%), δ-cadinene (4.21%) and γ-terpinene (4.11%). The antioxidant activity of T. boveana essential oil and organic extracts (hydroalcoholic, CHCl₃, AcOEt, n-BuOH) was evaluated by different tests, including DPPH, ABTS, phenanthroline, SNP and ferric reducing power. The findings indicated that T. boveana essential oil possesses moderate antioxidant capacity, with IC₅₀ values of 223.59 ± 1.01 μg/mL according to the DPPH test. The extracts and essential oil also demonstrated notable inhibitory impacts against α-amylase and butyrylcholinesterase. Antimicrobial activity was determined regarding four bacterial strains, determining the minimum inhibitory concentrations (MICs) and bactericidal concentrations (MBCs). The geometry and electronic properties of the main EO compounds were determined using density functional theory (DFT) calculations. Furthermore, docking studies were conducted to investigate the interaction and binding affinity of these molecules with the active sites of BuChE and α-amylase enzymes. The results highlight the value of Tamarix boveana as a medicinal plant and indicate its effectiveness as an important source of bioactive compounds for many uses. Full article

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. Cefmetazole (CMZ) and flomoxef (FMOX) are parenteral antibiotics that are widely used in Japan and have emerged as potential carbapenem alternatives. Repositioning these agents effectively addresses the clinical need for carbapenem-sparing strategies and outpatient ESBL-E management. This review aims to reposition CMZ and FMOX for real-world clinical practice by synthesizing basic research, clinical studies, and pharmacokinetics/pharmacodynamics (PKs/PDs) analyses, which suggest that these agents may be effective in treating ESBL-E infections—particularly urinary tract infections, as evidenced by their minimum inhibitory concentration (MIC) values. The clinical outcomes of these interventions have been comparable to those of carbapenems, which support their role in antimicrobial stewardship. Their PK/PD characteristics emphasize the importance of dose optimization to ensure therapeutic efficacy, whereas recent insights into resistance mechanisms provide a foundation for appropriate use. As novel antibiotic development takes substantial time, revisiting existing options is increasingly important. Notably, the Infectious Diseases Society of America’s 2024 guidance on antimicrobial resistance has omitted CMZ and FMOX, owing to which clinicians have limited guidance on their use, particularly in regions like Japan where these antibiotics are widely employed. By addressing this knowledge gap, the present review offers a comprehensive evaluation of these drugs and highlights their potential as intravenous agents in ESBL-E management. Furthermore, it highlights the ongoing challenge of ensuring effective oral step-down therapy in an outpatient setting to reinforce the global relevance of CMZ and FMOX in a broader treatment framework, underscoring their potential for outpatient administration where clinically appropriate. Full article

Increased bacterial resistance to current antibiotics leads to a depletion of therapeutic options in medicine. One of the problems of current therapy is methicillin-resistant Staphylococcus aureus (MRSA), which, in addition to resistance to β-lactam antibiotics, is multidrug-resistant. Some strains can also produce biofilms, a multicellular structure that is resistant or tolerant to various antibiotics. In hospitals worldwide, about 15% of invasive infections are caused by MRSA. Extracts of Rubus caesius (dewberry) contain high concentrations of compounds such as phenolic acids, flavonoids, tannins, and anthocyanins, which have potential antibacterial properties. This study is the first to demonstrate the activity of aqueous and ethanolic extracts of dewberry leaves (L_H2O, L_EtOH) and stems (S_H2O, S_EtOH) against S. aureus and Staphylococcus epidermidis. The most active extracts were L_EtOH (MIC 0.16 ± 0.40–1.56 ± 0.23 mg/mL) and L_H2O (MIC 0.16 ± 0.20–10 mg/mL). The study showed that L_EtOH, S_EtOH and L_H2O extracts inhibited biofilm formation by clinical strains MRCN (methicillin-resistant coagulase-negative staphylococci) and MRSA (biofilm biomass reduction from 40 to 100%). Furthermore, 3,3′—dipropylthiacarbocyanine (DiSC₃(5)) and N-phenyl-naphthylamine (NPN) were used to show that L_EtOH and S_EtOH caused the membrane depolarization of the strains studied. We also showed that the extracts acted synergistically and additively with cefoxitin and amikacin, reducing the MIC values of the antibiotics used by 8- to 16-fold and of the extracts tested by 4- to 8-fold. This study provides new data on potential antibacterial drugs of therapeutic importance. Full article

Achillea nobilis represents a species of considerable medicinal importance within the Asteraceae family, historically employed in Central Asia and various Eurasian territories for the management of inflammatory, microbial, and gastrointestinal ailments. Notwithstanding its extensive ethnopharmacological significance, the phytochemical profile and pharmacological attributes of its various anatomical components have not been comprehensively investigated. This research endeavor sought to delineate the phytochemical constituents and evaluate the antimicrobial efficacy of ethanol extracts derived from both the aerial and root segments of A. nobilis. Qualitative phytochemical analysis and GC–MS characterization unveiled a diverse array of bioactive compounds, encompassing flavonoids, phenolic compounds, organic acids, lactones, alcohols, and heterocyclic derivatives. In particular, the aerial oil extract exhibited the presence of terpenoids, fatty acids and their esters, sterols, hydrocarbons, and minor organosilicon and cyclobutanone derivatives, with notable compounds such as linoleic acid (8.08%), 6-tetradecyne (14.99%), isopropyl linoleate (14.64%), and E,Z-1,3,12-nonadecatriene (22.25%). In vitro antimicrobial activity was assessed against eight clinically relevant microbial strains employing the broth microdilution technique. The aerial ethanol extract exhibited pronounced antimicrobial properties, particularly against MRSA and C. albicans, with MICs ranging from 0.5 to 2 mg/mL, whereas the root ethanol extract displayed MICs of 1 to 3 mg/mL. Additionally, the aerial oil extract showed moderate inhibitory activity, with MIC values ranging from 1.5 to 3 mg/mL, demonstrating effectiveness particularly against C. albicans, C. neoformans, and MRSA. These findings underscore the therapeutic potential of A. nobilis, particularly its aerial component, as a viable natural source of antimicrobial agents. Full article

Antimicrobial resistance is a threat to probiotic microorganisms due to their potential role in harboring and transmitting resistance genes. This study focuses on two Bifidobacterium species (B. animalis subsp. lactis and B. longum) by analyzing 657 Minimal Inhibitory Concentration (MIC) values extracted from research articles indexed in Scopus, PubMed, and Web of Science, published since 2014, and considering 17 different antibiotics. MIC values were used for descriptive statistical analysis (boxplots and violin plots) to evaluate both inter- and intraspecies distributions. The results showed an overall increase in MIC values compared to historical data, with B. longum exhibiting high resistance to tetracyclines and streptomycin—approximately 25% to 50% of the strains had MIC values > EFSA cut-offs. The violin plots revealed the presence of resistant subpopulations, particularly within B. longum. These findings support the relevance of longitudinal MIC analysis as a tool for detecting early shifts in antimicrobial susceptibility and highlight the importance of data-driven approaches for microbiological risk assessment in probiotic applications. Full article

The objectives of this study were to design, synthesize, and evaluate the antibacterial activity of a series of novel aminoguanidine-tetralone derivatives. Thirty-four new compounds were effectively synthesized through nucleophilic substitution reaction and guanidinylation reaction. Chemical structures of all the desired compounds were identified by NMR and HR-MS spectroscopy. Most of the synthesized compounds showed significant antibacterial activity against ESKAPE pathogens and clinically resistant Staphylococcus aureus (S. aureus) isolates. S. aureus is an important pathogen that has the capacity to cause a variety of diseases, including skin infections, pneumonia, and sepsis. The most active compound, 2D, showed rapid bactericidal activity against S. aureus ATCC 29213 and MRSA-2 with MIC/MBC values of 0.5/4 µg/mL and 1/4 µg/mL, respectively. The hemolytic activity and cytotoxicity of 2D was low, with HC₅₀ and IC_{50(HEK 293-T)} values of 50.65 µg/mL and 13.09 µg/mL, respectively. Compound 2D induced the depolarization of the bacterial membrane and disrupted bacterial membrane integrity, ultimately leading to death. Molecular docking revealed that dihydrofolate reductase (DHFR) may be a potential target for 2D. In the mouse skin abscess model caused by MRSA-2, 2D reduced the abscess volume, decreased bacterial load, and alleviated tissue pathological damage at doses of 5 and 10 mg/kg. Therefore, compound 2D may be a promising drug candidate for antibacterial purposes against S. aureus. Full article

Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assessed their synergistic effects with amphotericin B (AmB). Methods: In this study, five selected naphthoquinones were evaluated for their antifungal activity against Cryptococcus spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. Results: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. Conclusions: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against Cryptococcus spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis. Full article

Background: Antimicrobial resistance (AMR) is an escalating concern in both human and veterinary medicine, particularly in the poultry sector, where antibiotic usage is substantial. Streptococcus spp. and Staphylococcus aureus are important pathogens in waterfowl, causing systemic infections. However, there is a significant lack of data regarding their antimicrobial susceptibility patterns in waterfowl populations. This study aims to address this gap by determining the minimum inhibitory concentrations (MICs) of isolates from Hungarian waterfowl farms and evaluating resistance patterns in clinical isolates. Methods: A total of eight S. aureus and 19 Streptococcus isolates were collected from ducks and geese between 2022 and 2023. Antimicrobial susceptibility testing was performed for 15 antimicrobials using the broth microdilution method. Potential associations between MIC values were analyzed using Spearman’s rank correlation test. Results: High MIC values were observed for tetracyclines, phenicols, and fluoroquinolones, in the case of Streptococcus, with 89.5% of isolates exhibiting resistance to doxycycline, 63.2% to florfenicol, and in the case of S. aureus, 25.0% to enrofloxacin. In the case of Streptococcus, a strong positive correlation was identified between tylosin and tiamulin (0.88, p < 0.001), as well as between tylosin and lincomycin (0.75, p < 0.001). A moderate correlation was observed between doxycycline and spectinomycin (0.72, p = 0.03), suggesting potential co-selection mechanisms. Conclusions: Our findings emphasize the necessity of continuous AMR surveillance in the waterfowl industry, particularly for multidrug-resistant strains. Understanding cross-resistance patterns is crucial for developing targeted control measures, and future studies should incorporate whole-genome sequencing to elucidate resistance determinants and co-selection mechanisms. This study highlights the potential public health and veterinary risks associated with AMR in waterfowl and reinforces the importance of responsible antibiotic use and the development of alternative therapeutic strategies in veterinary practice. Full article

Background:Riemerella anatipestifer and Erysipelothrix rhusiopathiae remain clinically significant pathogens in the waterfowl industry, causing substantial economic losses and posing potential zoonotic risks. Antimicrobial resistance (AMR) continues to spread in the poultry sector, making regular surveillance of bacterial isolates essential. Methods: In this study, eight R. anatipestifer and eighteen E. rhusiopathiae strains were isolated from clinical cases in Hungarian waterfowl between 2022 and 2023. Minimum inhibitory concentration (MIC) values were determined for antibiotics of veterinary and public health significance. Results: For R. anatipestifer, high resistance rates were observed for spectinomycin, lincomycin, and tiamulin, while beta-lactam antibiotics (amoxicillin, ceftriaxone, and imipenem) demonstrated strong efficacy. Among the E. rhusiopathiae isolates, resistance to amoxicillin (89%) and enrofloxacin (61%) was notable, whereas ceftriaxone and doxycycline exhibited moderate antibacterial effects. Conclusions: Our findings underscore the importance of targeted antimicrobial use in the waterfowl industry. Beta-lactam antibiotics remain effective, whereas rising resistance to fluoroquinolones and aminoglycosides raise serious concerns. Routine AMR surveillance and the adoption of alternative strategies are crucial for controlling infections and maintaining flock health. Full article

Staphylococcus aureus and coagulase-negative staphylococci (CNS) are the main causative agents of mastitis in sheep. Their ability to form biofilms in vivo is considered an important virulence factor underlying mastitis outbreaks refractory to antibiotic treatments. Furthermore, pre- and postdipping immersion during milking in iodine substances could determine the presence of residues in milk and therefore represent a health risk factor for consumers. The aim of this study was to evaluate the antibacterial and biofilm inhibitory activity of Thymus vulgaris L. essential oil (TEO) against staphylococci strains isolated from ovine clinical mastitis. In particular, 3 reference strains (S. aureus 25923 and 11623 and S. epidermidis 12228) and 12 clinical isolates (6 S. aureus and 6 CNS) were used. TEO solutions, from a concentration of 1% (v/v) to 1.25% (v/v), corresponding to 9.28–2.32 mg/mL, were obtained after solubilization in 10% dimethyl sulfoxide (DMSO) and used to evaluate the bacterial time-kill compared to that of an iodine-based solution. Antibacterial efficacy was then assessed by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), while biofilm inhibition was assessed by minimum biofilm inhibitory concentration (MBIC) using a spectrophotometer at a wavelength of 570 nm. Additionally, biofilm-associated genes (icaA and icaD) were evaluated in all tested strains by PCR. The tested TEO concentrations were able to significantly and prominently reduce bacterial growth compared to controls, as demonstrated by bacterial time-kills. The MIC value was obtained at a concentration of 0.50% (v/v) for a single coagulation-positive isolate (S. aureus (f)) and at a concentration of 0.25% (v/v) for all other isolates. TEO showed effective bactericidal action with a 99.9% reduction in CFU/mL of all isolates in the MBC test at a concentration of 0.25% (v/v) for most of the tested strains. Furthermore, a marked inhibition in biofilm formation at all tested concentrations was observed, with MBIC value of 0.25%. All S. aureus tested were biofilm-producing strains and positive for icaA and icaD genes, while two CNS biofilm-producing strains were negative for both genes. These preliminary results suggest that TEO could be a promising alternative as an udder disinfectant during milking practices. Although in vivo studies are needed to confirm the efficacy and safety of TEO as an adjuvant in the prevention and treatment of udder infections, TEO could help counteract the emergence of antimicrobial resistance and reduce the potential risk of iodine residues in milk. Full article

Background: The global spread of antimicrobial resistance is one of the defining challenges of our time. Preserving the efficacy of antibiotics is a shared responsibility, which includes conducting regular surveillance studies. The poultry industry, which produces the highest quantity of animal-derived protein in the shortest time, faces significant challenges from Escherichia coli, a bacterium frequently responsible for clinical disease. Methods: This study aimed to assess the susceptibility of E. coli isolates collected from clinical cases in turkeys across Hungary to antibiotics of veterinary and public health importance using minimum inhibitory concentration (MIC) determination. Results: Over the course of one year, we analyzed a total of 70 clinical isolates. Most isolates (64.3%) were resistant to amoxicillin, and the observed 25.7% resistance to amoxicillin–clavulanic acid suggests that the majority of strains are beta-lactamase producers. The highest resistance level was observed against neomycin (74.3%). Resistance to critically important antibiotics, including enrofloxacin (28.6%), ceftriaxone (8.6%), and colistin (7.1%) raises significant public health concerns. When comparing our results with human hospital resistance data from Hungary, most findings showed comparable values, with the exception of neomycin, which exhibited markedly higher resistance in the isolates from poultry. Conclusions: Our findings underscore the necessity of regular surveillance studies, which should be periodically repeated in the future to observe temporal trends. These results should also be linked to antibiotic usage patterns, and the genetic background of multidrug-resistant strains should be further examined using next-generation sequencing techniques. This study provides critical insights into the current antimicrobial resistance landscape in the Hungarian poultry industry and highlights the urgent need for targeted interventions to prevent the dissemination of resistant strains to humans. The findings contribute valuable data for developing future AMR management strategies in veterinary and public health contexts. Full article

Background/Objectives: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an important pathogen associated with high mortality and treatment failure rates. We aimed to assess the susceptibility of CRPA to antipseudomonal agents, identify its resistance mechanisms, and evaluate clinical outcomes in a sample of CRPA isolates. Methods: This was an in vitro study of a clinical isolate of CRPA from hospitalized patients with CRPA infection and a retrospective observational study of these patients, who were diagnosed between 14 February 2021 and 10 August 2023 at Songklanagarind Hospital in Songkhla, Thailand. In vitro experiments were conducted to determine the minimum inhibitory concentrations (MICs) of the antipseudomonal agents using the broth microdilution method. Resistance mechanisms were assessed using the modified carbapenem inactivation method, combined disk tests, and quantitative real-time reverse transcription polymerase chain reaction. Results: A total of 140 CRPA isolates were analyzed. Both traditional and novel β-lactams had high MICs. The most common resistance mechanism was the upregulation of the MexAB-OprM efflux pump (81.3%), followed by the downregulation of the OprD porin (48.9%) and metallo-β-lactamase (MBL) production (45.0%), and the overexpression of bla_AmpC (41.0%). The 30-day all-cause mortality rate was 30.5%. The risk factors associated with 30-day mortality included a Charlson Comorbidity Index of ≥5 (OR: 3.43; 95% CI: 1.07–10.99; p = 0.03), sepsis (OR: 10.62; 95% CI: 1.26–89.44; p = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67–11.55; p < 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04–0.74; p = 0.01). Conclusions: This study revealed higher MIC values of all β-lactams for CRPA, while colistin and amikacin remained effective. The resistance mechanisms included MexAB-OprM overexpression, OprD downregulation, MBL production, and bla_AmpC overexpression, with a higher prevalence of MBL than in other regions of Thailand. High 30-day mortality was associated with comorbidities, sepsis, and septic shock, but active therapy reduced mortality. Full article

Background/Objectives: Responsiveness and minimal important change (MIC) are key metrics that vary across conditions and should be determined for specific populations. However, these metrics have not yet been established for the Mini-Balance Evaluation Systems Test (Mini-BESTest) and Brief-BESTest in people with subacute traumatic incomplete cervical spinal cord injury (iCSCI). In this study, we aimed to determine the responsiveness and MIC of the Mini-BESTest and Brief-BESTest in people with subacute iCSCI. Methods: This study included people with iCSCI who could maintain the standing position for 30 s without assistance within 7 days of injury at the university hospital’s advanced critical care center. Responsiveness was assessed by correlating Mini-BESTest and Brief-BESTest change scores with the Berg Balance Scale (BBS). MIC values were determined using the global rating of change scale as an anchor, employing receiver operating characteristic curve methods (MIC_ROC) and predictive modeling methods adjusted for the proportion of improved participants (MIC_adjusted). Results: Fifty people with iCSCI were included in the analysis. Changes in BBS scores were moderately positively correlated with changes in Mini-BESTest and Brief-BESTest scores. MIC_adjusted values were 3.7 for the Mini-BESTest and 2.2 for the Brief-BESTest. The MIC_ROC, based on an improvement rate of 64%, was deemed less appropriate for interpreting meaningful changes due to the high proportion of improved participants. Conclusions: MIC_adjusted benchmarks can help clinicians measure significant improvements in dynamic balance, design effective interventions, and evaluate rehabilitation outcomes in people with iCSCI. Full article