Search Results (695)

Metronidazole (MTZ), a widely used antiamoebic and antibacterial drug, has been linked to male reproductive damage. The aim of this study was to investigate Olea europaea L. and Equisetum arvense L. ethanol extracts for the protection against testicular toxicity and male infertility caused by MTZ, and to characterize the underlying mechanisms. Forty-two male rats were divided into six groups. The animals in group 1 served as the controls and received a daily oral dose (1 mL) of the vehicle. The animals in group 2 received metronidazole at doses of 400 mg/kg. Group 3 was treated with E. arvense extract at doses of 100 mg/kg. Group 4 was treated with O. europaea leaf extract at doses of 400 mg/kg. Group 5 was treated with metronidazole and E. arvense extract at doses of 400 and 100 mg/kg, respectively. Group 6 was treated with metronidazole with O. europaea leaf extract at doses of 400 and 400 mg/kg, respectively. The rats were given a daily oral dose of different treatments for 60 days, after which the animals were euthanized to study the histopathological and molecular changes in the testis and the sperm count in the epididymis. The testosterone levels, MDA levels, and GSH contents were also assessed in the rats in all groups. The findings revealed that the MTZ treatment caused a substantial increase in MDA levels and upregulated the NBN gene expression relative to the control. Moreover, the MTZ treatment produced significant reductions in the sperm count and viability, testosterone levels, and GSH content, and downregulated the INSL-3, STAR, HSD-3β, and CYP11A1 gene expression compared to the control. The adverse effects in testicular tissue were significantly reduced in rats given the O. europaea leaves and E. arvense treatment. The findings may show that MTZ can enhance testicular toxicity and infertility, but both plant extracts can prevent these harmful consequences. Full article

Tetanus is a life-threatening neurological disease affecting vertebrate species, including primates. Here, we present a case of severe generalized tetanus in a juvenile male chimpanzee (Pan troglodytes) that was rescued from the illegal wildlife trade and admitted to a rehabilitation center in the Republic of Congo. Upon arrival, the chimpanzee presented with deep, contaminated constrictive wounds, trismus, generalized rigidity, and stimulus-induced tonic spasms accompanied by transient apnea, while remaining conscious. A presumptive clinical diagnosis was made, after which integrated care began immediately. This included meticulous wound debridement and irrigation, passive immunization with antitoxin, initiation of active immunization, metronidazole with adjunctive penicillin G, diazepam-based spasm control, multimodal analgesia, and low-stimulation nursing with oxygen supplementation, enteral nutrition, and temporary urinary catheterization. Aerobic wound culture yielded mixed flora, and a Gram stain of the feces showed large Gram-positive rods with terminal spores. Hematology tests revealed leucopenia with neutropenia and severe thrombocytopenia. The spasms ceased by day 5, at which point the diazepam dose was reduced and oral intake was increased. By week 8, he had made a full clinical recovery and was successfully reintegrated into his group. This case supports the use of pragmatic, sanctuary-adapted protocols and systematic vaccination. Full article

Background and Clinical Significance: Henoch–Schönlein purpura (HSP), also known as Immunoglobulin A (IgA) vasculitis (IgAV), is a common systemic vasculitis in children characterized by palpable purpura, abdominal pain, and joint and kidney involvement. While respiratory tract viral or bacterial infections are the most common causes of HSP, parasitic infections, such as giardiasis, are occasionally reported. Giardia lamblia is the most common parasite infecting humans and a major cause of infectious diarrhea, which can lead to post-infection complications. To our knowledge, this is the first report in Greece describing a pediatric patient with HSP secondary to giardiasis. A review of pediatric HSP cases caused by parasitic infections is also included. Case presentation: An 8-year-old girl presented with a purpuric rash, joint tenderness, severe abdominal pain, and bloody diarrhea, raising suspicion of HSP. Laboratory tests revealed elevated IgA levels, and stool analysis tested positive for Giardia lamblia antigen. The diagnosis of HSP secondary to giardiasis was confirmed, and the patient was successfully treated with supportive care, metronidazole, and corticosteroids. Conclusion: This case report and literature review highlight parasitic infections as an underrecognized but important trigger of pediatric HSP. Although giardiasis is linked to various post-infectious complications, its association with HSP is rarely reported. Pediatricians should maintain a high level of suspicion for underlying infectious diarrhea, such as giardiasis, in patients with HSP, especially in children with prominent gastrointestinal symptoms. Early recognition can reduce complications and facilitate faster recovery. Further research is needed for the immunopathogenic mechanisms linking parasitic infections and HSP in children. Full article

Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been linked to atherosclerosis development. The clinical failure of antibiotics to improve cardiovascular outcomes necessitates alternative explanations. This study examines how sub-inhibitory concentrations of metronidazole affect the biogenesis and pathogenic potential of P. gingivalis extracellular vesicles (EVs) on human umbilical vein endothelial cells (HUVECs). EVs were isolated from both untreated bacteria (N-EVs) and those treated with sub-inhibitory concentrations of metronidazole (M-EVs) through ultracentrifugation. Characterization included transmission electron microscopy (TEM), nanoparticle tracking analysis, and Western blotting for virulence factors. HUVECs were evaluated using viability, migration, cell death assays, ROS detection, NF-κB activation imaging, and cytokine measurement. Sub-inhibitory concentrations of metronidazole increased EV production by 2.3-fold and enriched M-EVs with virulence factors (lipid A LPS, Kgp, RgpA). M-EVs demonstrated significantly stronger cytotoxicity, causing greater impairment of HUVEC viability and migration, alongside increased cell death. Mechanistically, M-EVs induced elevated mitochondrial and cellular ROS, promoting NF-κB activation and enhancing secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Sub-inhibitory concentrations of metronidazole exacerbate endothelial injury by amplifying EV production and virulence factor loading in P. gingivalis, offering a mechanistic explanation for the limited cardiovascular benefits of antibiotic therapy in periodontitis patients. Full article

Background/Objectives: In surgical antibiotic prophylaxis (SAP), most studies continue to report the number of prescriptions aggregated at the hospital level, rarely integrating the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) classes with standardized volume indicators. This study aimed to evaluate the utilization of antibiotics for SAP in a large Italian teaching hospital using both the number of prescriptions and defined daily doses (DDDs) and mapped the AWaRe models across different surgical specialties to highlight differences relevant to management. Methods: We conducted a prospective hospital-wide surveillance of all consecutive patients undergoing surgical procedures between March and May 2023 at the Azienda Ospedaliero-Universitaria delle Marche. Data included demographics, surgical specialty, and all antibiotic administrations with indication. For SAP, each prescription was classified according to the 2023 WHO AWaRe framework, and consumption was quantified using the WHO ATC/DDD methodology. Results: A total of 914 patients were monitored, with complete antibiotic data for 793 (86.8%). Among 433 SAP prescriptions, the most frequently used agent was cefazolin (82%), followed by amoxicillin/β-lactamase inhibitor (5%) and metronidazole (5%). According to AWaRe, 93% of SAP prescriptions were Access agents and 7% were Watch agents; no Reserve antibiotics were used. When expressed in DDDs (total: 443.5), 87.8% were Access and 12.2% Watch. Cefazolin accounted for over 85% of Access DDDs. Conclusions: By combining AWaRe classes with DDDs and resolving results by surgical specialty, this study extends hospital-level metrics and provides a pragmatic framework for SAP benchmarking. The predominance of Access agents is consistent with management objectives, while differences across specialties identify concrete tools for local quality improvement. Full article

Background/Objectives: Although several studies have reported antibiotic protocols for the prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive and/or antiangiogenic therapy following tooth extraction, it remains unclear which protocol is the most effective. Accordingly, this scoping review analyzed antibiotic use in dental extractions in these patients, focusing on whether antibiotic duration influences MRONJ occurrence. Methods: Two authors independently searched PubMed, Scopus, and Web of Science (2003–2025). Out of the 770 studies screened, 36 were included. Descriptive statistics, a meta-analysis comparing MRONJ incidence in patients treated with high-dose (HD) and low-dose (LD) antiresorptive treatment according to the therapeutic indication and generalized linear mixed models on antibiotic duration were obtained (α = 0.05). Results: Amoxicillin, alone or with clavulanic acid, was the most used antibiotic, and in 8 studies it was combined with metronidazole. Seven studies reported parenteral antibiotic administration. Median antibiotic duration was 1.5 days pre-extraction, 5.5 days post-extraction, and 7 days overall. MRONJ risk was significantly higher in HD than LD patients (95% CI: 1.46–5.43; p = 0.002), and antibiotic duration was positively associated with reduced MRONJ risk in HD patients (β = –0.15, p = 0.026; OR = 0.86, 95% CI: 0.75–0.98). Conclusions: The literature shows heterogeneous antibiotic protocols for MRONJ prevention. The increased MRONJ risk and greater protective effect of antibiotics in HD patients suggest that patient risk profile may be more relevant than the antibiotic regimen. Full article

Background: Antimicrobial resistance (AMR) is now a critical issue in South Africa, enhanced by considerable inappropriate prescribing of antibiotics. There is currently variable dispensing of antibiotics without a prescription. Where this occurs, it is principally for urinary tract infections (UTIs) and sexually transmitted infections (STIs). Consequently, there is a need to comprehensively evaluate antibiotic dispensing patterns and factors influencing this to reduce AMR. Methods: A previously piloted questionnaire was administered to patients exiting three different categories of community pharmacies in a rural province. The questionnaire included data on the prevalence of antibiotics dispensed, whether without a prescription, and the rationale for this. Results: A total of 465 patients leaving community pharmacies with a medicine were interviewed. 54.4% of interviewed patients were dispensed at least one antibiotic, with 78.7% dispensed these without a prescription from either independent or franchise pharmacies. Metronidazole (36.1%) and azithromycin (32.7%) were the most dispensed antibiotics. STIs were the most common infectious disease for which an antibiotic was dispensed (60.1%), with 99.6% dispensed without a prescription. Upper respiratory tract infections (URTIs) were the most common infection where antibiotics were dispensed with a prescription (60.0%), with little dispensing without a prescription (7.1%). The most frequently cited reasons for obtaining antibiotics without a prescription were prior use (56.8%), long waiting times at PHC clinics (15.6%), and financial constraints (6.0%). Conclusions: There is an urgent need to review community pharmacists’ scope of practice, including allowing them to prescribe antibiotics for infectious diseases such as UTIs, similar to other countries. Concomitantly, utilise trained community pharmacists to engage with prescribers to improve future antibiotic use, especially for URTIs. Full article

Background: Acute pancreatitis is a significant global disease. This study investigated the phytochemical composition and potential protective effects of Equisetum arvense L. (horsetail) ethanol extract and Olea europaea L. (olive leaves) aqueous extract against metronidazole (MTZ)-induced pancreatic damage in rats. Materials and Methods: Rats were randomly divided into six groups: Group I (control) received saline; Group II (Metronidazole) received only MTZ (400 mg/kg). Group III (Equisetum arvense group) received E. arvense 100 mg/kg. Group IV (Olea europaea) received 400 mg/kg of O. europaea. Group V (MTZ + E. arvense) received both MTZ (400 mg/kg) and E. arvense (100 mg/kg). Group VI (MTZ + O. europaea) received MTZ (400 mg/kg) and O. europaea (400 mg/kg). All treatments were delivered daily via the oral route. After 60 days, serum amylase, lipase, protease, and glucose levels, oxidative parameters “malondialdehyde (MDA), catalase (CAT), mRNA relative expression of pancreatic Pik3ca (phosphatidylinosi-tol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), AKT (AKT Serine/Threonine Kinase 1), Nrf-2 (Nuclear factor, erythroid 2-like 2), TNFα (tumor necrosis factor alpha), and IL-1β (interleukin-1 beta genes, an apoptotic marker “caspase-3,” and histopathological changes were estimated. Results: HPLC analysis revealed that horsetail extract contained caffeic acid, catechin, rutin, and kaempferol, while olive leaf extract was dominated by oleuropein. MTZ administration significantly elevated serum levels of pancreatic enzymes (lipase, amylase, and protease) and glucose and increased oxidative stress markers, such as MDA, while reducing catalase (CAT) activity. Co-treatment with MTZ and horsetail, or MTZ and olive extracts, mitigated these effects, especially horsetail, which restored CAT levels and reduced MDA concentrations. qPCR analysis showed MTZ upregulated inflammatory genes (TNFα, IL-1β) and downregulated antioxidant and survival-related genes (Pik3ca, AKT, Nrf-2). Horsetail co-treatment significantly reversed these gene expression patterns. Histopathological and immunohistochemical analyses confirmed MTZ-induced pancreatic tissue degeneration and increased cleaved caspase-3 expression, both of which were notably alleviated by horsetail extract. Conclusions: These findings highlight the superior protective efficacy of Equisetum arvense over Olea europaea in ameliorating MTZ-induced pancreatic toxicity, potentially through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. Full article

Background/Objectives: Helicobacter pylori infection remains a significant health concern, as increasing antimicrobial resistance compromises the efficacy of eradication. Understanding regional antimicrobial resistance profiles is crucial for optimizing eradication strategies. In this study, we aimed to evaluate the antimicrobial susceptibility patterns and identify the factors influencing H. pylori culture success. Methods: In this prospective study, 697 gastric tissue samples were collected from consecutive patients who underwent upper endoscopy between November 2023 and May 2025. Tissue samples obtained by forceps biopsy or recovered from rapid urease test kits were cultured for H. pylori. Antimicrobial susceptibility testing was performed using the agar dilution method; factors associated with successful culture were analyzed using logistic regression. Results: Among 488 patients with H. pylori infection, culture and antimicrobial susceptibility testing were successful in 387 (79.3%). The overall antimicrobial resistance rates were 17.8%, 27.1%, 29.5%, 0.3%, and 32.8% for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin, respectively. Notably, 27.6% (107/387) of the isolates were resistant to two or more antibiotics. Using multivariate analysis, the use of fresh biopsy tissue (odds ratio [OR]: 1.646, 95% confidence interval [CI]: 1.046–2.591, p = 0.031), transport interval (OR: 0.911, 95% CI: 0.853–0.973, p = 0.005), and presence of prior eradication therapy (OR: 0.318, 95% CI: 0.156–0.648, p = 0.002) were identified as significant predictors of culture success. Conclusions: The high rate of clarithromycin resistance underscores the need for susceptibility-guided eradication strategies in this region. Optimizing sample handling, particularly by minimizing transport time and using fresh biopsy tissue, may improve culture yields. Full article

In September 2024, an acute hemorrhagic diarrhea occurred in a colony of captive ring-tailed lemurs (Lemur catta) housed adjacent to an enclosure of squirrel monkeys in Henan Province, China. Three of the ring-tailed lemurs (1-year-old females) died, and necropsy revealed severe cecal hemorrhage. Histopathology demonstrated extensive mucosal necrosis, hemorrhage, and inflammatory cell infiltration in the cecum, with parasite adhesion and invasion into the crypts. Microscopic examination and PCR targeting the ITS1-5.8S-ITS2 region (347 bp) confirmed the presence of T. mobilensis in the deceased lemurs’ intestinal contents and in feces from 40.0% (4/10) of the squirrel monkeys. Ultrastructural analysis (SEM/TEM) confirmed that the isolated parasites exhibited the morphology and key features of T. mobilensis, including prominent peripheral hydrogenosomal vesicles. Treatment with metronidazole and supportive care led to the recovery of the surviving lemurs. Post-treatment fecal exams of ring-tailed lemur were negative for T. mobilensis. This report provides the first evidence of T. mobilensis infection in ring-tailed lemurs, indicating cross-species transmission from squirrel monkeys to lemurs, likely facilitated by keeper-mediated mechanical transmission via tools and footwear that were used in both enclosures. Full article

Background/Objectives: Guidelines recommend combination therapy with oral vancomycin and intravenous (IV) metronidazole for fulminant Clostridioides difficile infection (CDI). Although patients with severe CDI are often managed with combination therapy, evidence supporting this practice remains limited. This study was performed to compare the clinical outcomes of vancomycin monotherapy versus combination therapy in patients with severe CDI. Methods: We conducted a multicenter, retrospective, observational cohort study including adult patients with severe CDI who received oral vancomycin between January 2017 and May 2021. Patients were classified as receiving combination therapy if IV metronidazole was administered for at least 72 h within 48 h of initiating oral vancomycin; otherwise, they were classified as receiving vancomycin monotherapy. The primary outcome was a composite of inpatient all-cause death or colectomy within 60 days after CDI diagnosis. The secondary outcomes were the clinical cure rate, CDI recurrence rate, time to discharge after CDI diagnosis, and duration of ICU admission. Results: In total, 215 patients were included, with 100 (46.5%) receiving combination therapy. There were no significant differences in in-hospital mortality or colectomy between the monotherapy and combination therapy groups (25.2% vs. 26.0%, p = 1.00). Recurrence rates (19.1% vs. 16.8%, p = 0.81), total length of stay (31.0 vs. 23.0 days, p = 0.16), and ICU stay duration (35.0 vs. 32.0 days, p = 0.89) were also similar. However, the clinical cure rate was significantly higher in the monotherapy group than in the combination therapy group (79.1% vs. 65.0%, p = 0.03). Conclusions: Combination therapy with oral vancomycin and IV metronidazole was not associated with improved clinical outcomes in patients with severe CDI. Prospective randomized studies are needed to clarify optimal management strategies for severe CDI. Full article

The use of chitosan nanoparticles (CH-NPs) loaded with antibiotics as irrigants in endodontics offers a unique combination, demonstrating effective antibacterial activity and low toxicity. Therefore, the aim of this study was to develop chitosan nanoparticles loaded with metronidazole, ciprofloxacin, and minocycline for use as endodontic irrigants to improve antibacterial activity against Enterococcus faecalis and to evaluate their cytotoxicity in human dental pulp stem cells (hDPSCs). Methods: The CH-NPs loaded with antibiotics were synthesized and analyzed using Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet-visible spectroscopy (UV-Vis). Agar diffusion and microdilution assays were performed to determine the minimum inhibitory concentration (MIC), and a cytotoxicity assay was conducted to establish the median cytotoxic dose. Results: Peaks corresponding to the functional groups of the chitosan-antibiotic complex’s chemical structure were identified. A one-way ANOVA (p ≤ 0.05) with Tukey’s post hoc test was used to analyze the antibacterial effect. CH-NPs-ciprofloxacin showed the greatest antibacterial activity against E. faecalis in both agar diffusion and microdilution assays. CH-NPs-metronidazole demonstrated lower cytotoxicity against hDPSCs. CH-NPs-minocycline showed superior antibacterial effects compared to plain chitosan in microdilution assays, although they exhibited greater cytotoxicity. Conclusions: The ongoing search for an irrigating solution with effective antibacterial properties and low cytotoxicity could transform traditional techniques. However, this field is still developing and underexplored. It is essential to reevaluate decisions about irrigation solutions, as evidence on the use of chitosan nanoparticles with antibiotics is limited. This study provides valuable data for endodontics and is a crucial step for future research. Full article

The development of advanced semiconductor-based catalysts for the rapid degradation of emerging pharmaceutical pollutants in water remains a critical challenge in environmental science. In this study, we present the synthesis, characterization, and catalytic performance of zinc oxide (ZnO) microtetrapods decorated with plasmonic Ag nanoparticles. These microtetrapods have been designed to enhance piezo-, photo-, and piezo-photocatalytic degradation of metronidazole (MNZ), a persistent antibiotic contaminant. ZnO microtetrapods were synthesized by high-temperature pyrolysis and using atmospheric-pressure microwave nitrogen plasma, followed by photochemical deposition of Ag nanoparticles at various precursor concentrations (0–1 mmol AgNO₃). The structural integrity of the samples was confirmed through X-ray diffraction (XRD) analysis, while the morphology was examined using scanning electron microscopy with energy-dispersive X-ray analysis (SEM-EDX). Additionally, spectroscopic analysis, including Raman, electron paramagnetic resonance (EPR), and photoluminescence (PL) spectroscopy, was conducted to verify the successful formation of heterostructures with adjustable surface loading of Ag. It has been shown that ZnO microtetrapods decorated with plasmonic Ag nanoparticles exhibit Raman-active properties. A systematic evaluation under photocatalytic, piezocatalytic, and combined piezo-photocatalytic conditions revealed a pronounced volcano-type dependence of catalytic activity on Ag content, with the 0.75 mmol composition exhibiting optimal performance. In the presence of both light irradiation and ultrasonication, the optimized Ag/ZnO composite exhibited 93% degradation of MNZ within a span of 5 min, accompanied by an apparent rate constant of 0.56 min⁻¹. This value stands as a significant improvement, surpassing the degradation rate of pristine ZnO by over 24-fold. The collective identification of defect modulation, plasmon-induced charge separation, and piezoelectric polarization as the predominant mechanisms driving enhanced reactive oxygen species (ROS) generation is a significant advancement in the field. These findings underscore the synergistic interplay between plasmonic and piezoelectric effects in oxide-based heterostructures and present a promising strategy for the efficient removal of recalcitrant water pollutants using multi-field activated catalysis. Full article

Hemorrhagic septicemia (HS) is a fulminant bovine disease across Asia and Africa, yet Pasteurella multocida (P. multocida) isolated from yak is poorly reported. We isolated strain NQ01 from a fatal HS case in Xizang, China and identified it as P. multocida B:2 by morphology, Gram stain, and PCR (kmt1⁺, bcbD⁺, LPS L2). NQO1 formed smooth, non-hemolytic colonies. After Gram staining, the cells appeared as red rods with bipolar staining. Antimicrobial testing showed broad susceptibility to β-lactams, aminoglycosides, tetracyclines, fluoroquinolones, midecamycin, florfenicol, polymyxin, and vancomycin, with resistance to metronidazole, trimethoprim sulfamethoxazole, and clindamycin. Streptomycin and ofloxacin had intermediate activity. In mice, the intraperitoneal and intranasal LD₅₀ values were 40.64 CFU/mL and 9.53 × 10⁶ CFU/mL, respectively. The intranasal fatal cases were characterized by bacteremia with multifocal disseminated intravascular coagulation involving lung, liver, and spleen. The complete genome comprises a single 2.33 Mb chromosome (40.47% GC, 2115 CDS, no plasmids) with only one resistance gene (Eco_EFTu_PLV) and 28 virulence genes spanning adhesion (tadA, rcpA, ppdD, pilB, tuf/tufA, htpB, PM_RS00430, PM_RS00425, PM_RS08640), immune modulation (lpxB/C/D, msbB, manB, rfaE/F, gmhA/lpcA, kdsA, pgi, wecA, galE, bexD’, ABZJ_RS06285, ABD1_RS00310), and nutritional/metabolic factor (hgbA, hemR, hemN), plus a YadA-like factor. Phylogenetically, NQ01 clusters with regional B:2 bovine/yak isolates. Collectively, these data define NQ01 as a highly virulent, low-resistance yak isolate and a practical model for natural-route HS pathogenesis and targeted control in high-altitude pastoral settings yaks. Full article

Background/Objectives: The rising global prevalence of inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, has resulted in an increase in the number of affected patients requiring dental care. The heightened risk of Clostridioides difficile infection (CDI) in IBD patients, particularly when exposed to commonly used dental antibiotics, is attributable to their altered gut microbiota and frequent immunosuppressive therapy. The objective of this review is to evaluate current antibiotic strategies for dental management in IBD and to identify safe and effective alternatives that minimise CDI risk. Methods: A narrative review was conducted in accordance with the SANRA guidelines. A comprehensive analysis of literature sourced from PubMed, Embase, Scopus, and Google Scholar was conducted. Results: The available evidence suggests that first- and second-line dental antibiotics—amoxicillin, ampicillin, and clindamycin—carry the highest risk of CDI. In contrast, metronidazole, which exhibits a comparable antimicrobial spectrum, has been shown to possess significantly reduced CDI potential and minimal disruption of gut microbiota. The utilisation of emerging local delivery systems, such as platelet-rich fibrin (PRF), has the potential to further reduce systemic antibiotic exposure. The adjunctive use of probiotics, prebiotics and synbiotics has been demonstrated to have the capacity to maintain microbial balance during therapy. Conclusions: Tailored, microbiome-conscious antibiotic strategies are essential in dental management of IBD patients. Further clinical research is needed to develop evidence-based guidelines and validate promising adjunctive approaches. Full article