Search Results (96)

Tuberculosis (TB) continues to be the world’s deadliest infectious disease, with an estimated 10.8 million new cases reported in 2023, of which India alone accounted for 28% of the global burden. This study aims to evaluate the impact of tuberculosis on pulmonary function and exercise tolerance, and to examine how these impairments affect health-related quality of life (HRQoL). In a cross-sectional design, 96 bacteriologically confirmed TB patients and 96 age- and sex-matched community controls underwent spirometry, six-minute-walk test (6 MWT), and HRQoL evaluation. DR-TB was detected in 27 patients (28.1%): Isoniazid monoresistance 59.3%, rifampicin monoresistance 11.1%, and XDR-TB 29.6%. Dyspnoea (70.8%) and cough (37.5%) were the most commonly reported symptoms among TB patients. Mean values of FEV₁, FVC, and FEV₁/FVC were significantly lower in TB patients compared to controls (62.8%, 65.97%, and 70.08% vs. 82.55%, 80.09%, and 78.08%, respectively; p < 0.001). Recurrent or DR-TB was associated with reduced spirometric indices and 6 MWT distances (241 m vs. 358 m in drug-sensitive TB). St. George’s respiratory questionnaire (SGRQ) scores indicated significantly poorer health-related quality of life (HRQoL) in patients compared to controls across all domains—symptoms (23.7 vs. 10.7), activity (33.3 vs. 14.2), and impact (20.6 vs. 9.4; p < 0.05). SGRQ scores were inversely correlated with lung function parameters (r = −0.42 to −0.56). These findings underscore the persistent health burden TB poses post-therapy, highlighting the need for routine post-TB functional screening and robust DR-TB control to achieve End-TB goals. Full article

Background/Objectives: Drug-resistant tuberculosis (DR-TB) presents significant challenges to public health, particularly in rural South Africa, where limited infrastructure, high HIV co-infection rates, and weak clinical governance contribute to poor treatment outcomes. This study evaluates treatment trajectories and the impact of clinical governance and public health interventions on DR-TB outcomes in the rural Eastern Cape. Methods: A retrospective cohort study was conducted among 323 laboratory-confirmed DR-TB patients treated between 2018 and 2021. Kaplan–Meier curves and Cox proportional hazards analysis identified predictors of unfavorable outcomes. Logistic regression analysis simulated the impact of enhanced clinical governance scenarios on treatment success. Results: Treatment outcomes included cure (36.2%), completion (26.0%), loss to follow up (LTFU) (9.0%), death (9.3%), failure (2.2%), and transfer (9.3%). The median treatment duration was 10 months (IQR: 9–11). Survival analysis indicates the highest risk of death and LTFU occurred in the first 6–8 months of treatment. Multivariate Cox regression revealed that primary (HR = 0.39; 95% CI: 0.23–0.68; p = 0.0017) and secondary education (HR = 0.50; 95% CI: 0.31–0.85; p = 0.0103) were significantly protective. Paradoxically, patients with pre-XDR (HR = 0.13; p = 0.034) and XDR TB (HR = 0.16; p = 0.043) showed lower hazard of poor outcomes, likely due to early mortality or referral. HIV-negative status was associated with higher risk of poor outcomes (HR = 1.74; p = 0.010). Simulations suggested that improved clinical governance via better follow-up, TB/HIV integration, and adherence support could improve treatment success by up to 20 percentage points in high-impact scenarios. Conclusions: Strengthening clinical governance through targeted interventions could substantially reduce LTFU and mortality, especially in vulnerable subgroups. A coordinated, patient-centered approach is critical for improving DR-TB outcomes in rural, high-burden settings. Full article

Background: Accurate and rapid diagnosis of drug-resistant tuberculosis is essential for initiating appropriate treatment and preventing the transmission of these strains. This study compares phenotypic and genotypic methods of drug susceptibility testing for Mycobacterium tuberculosis (M. tuberculosis). Methods: Resistance to first-line drugs, as well as resistance to second-line drugs (fluoroquinolones and aminoglycosides), was assessed using the Löwenstein–Jensen medium phenotypic method and the GenoType MTBDRplus genotypic method and analyzed. Results: The phenotypic resistance rate was 84.85% for INH (n = 56), 46.97% for RIF (n = 31), 48.48% for STR (n = 32), and 30.30% for EMB (n = 20). Of the MDR-TB isolates (n = 29), 41.37% were resistant to fluoroquinolones (n = 12) and 31.03% were resistant to both fluoroquinolones and injectable aminoglycosides, being classified as XDR-TB (n = 9). In addition, 22.73% of the MDR-TB isolates were resistant to all four first-line drugs (n = 15). The overall concordance between the line probe assay method and phenotypic testing was 94.74% for RIF and 95.16% for INH. Discordances were identified in three cases for RIF and two cases for INH, where isolates were reported as susceptible by GenoType MTBDRplus, but phenotypically resistant. Conclusions: Genotypic testing using GenoType MTBDRplus provides rapid and accurate results, but some cases of phenotypic resistance are not detected by this method. The results highlight the importance of using combined phenotypic and genotypic methods for accurate diagnosis of MDR-TB, as well as the need to integrate genomic sequencing to improve diagnostic accuracy. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis complex (MTBC), remains a global health challenge and can lead to severe pulmonary and extrapulmonary complications. Multidrug-resistant TB (MDR-TB) poses additional challenges, requiring advanced diagnostic and treatment strategies. This study evaluates the BD MAX MDR-TB molecular test for a rapid diagnosis of MDR-TB, detecting resistance to rifampicin (RIF) and isoniazid (INH). The BD MAX MDR-TB test, utilizing real-time PCR, was used to analyze specimens collected from TB-suspected patients, identifying MTB DNA and mutations associated with rifampicin and isoniazid resistance. Results were compared with traditional drug susceptibility testing, and 79 out of 638 samples tested were positive for MTB DNA, with 65 showing a sufficient amount of genetic material for resistance gene identification. The BD MAX test showed a 100% correlation with phenotypic rifampicin resistance, though discrepancies were noted for isoniazid resistance, with a 93% concordance. The BD MAX MDR-TB test is an effective tool for a rapid diagnosis of MDR-TB, especially for rifampicin resistance. However, it may not detect certain mutations related to isoniazid resistance. Complementary tests like Xpert MTB/XDR or whole-genome sequencing could improve diagnostic accuracy and support more effective TB control strategies. Full article

Hearing loss (HL) is a major global health concern, with drug-induced ototoxicity contributing significantly, particularly in patients undergoing treatment for drug-resistant tuberculosis (DR-TB). In South Africa, where both TB and HIV are prevalent, the risk of treatment-related auditory damage is especially high. This study aimed to assess the prevalence and predictors of hearing impairment among DR-TB patients in rural Eastern Cape, South Africa. A retrospective analysis was conducted on 438 DR-TB patients treated between 2018 and 2020, using pure tone audiometry (PTA) to assess hearing status post-treatment. Demographic, clinical, and lifestyle data were extracted from patient records and analyzed using logistic regression. The overall prevalence of hearing loss was 37.2%. Risk was significantly associated with an older age, a male gender, DR-TB classification (MDR, pre-XDR, and XDR), unsuccessful treatment outcomes, and substance use. Prevalence of HL increased notably in patients aged 70 and older. Lifestyle factors, particularly combined use of tobacco, alcohol, and drugs, were linked to higher odds of HL. These findings underscore the need for routine audiometric screening and personalized treatment monitoring in DR-TB care, especially for high-risk populations. Early identification of ototoxicity risk factors can inform safer treatment regimens and improve patient outcomes in resource-limited settings. Full article

Tuberculosis (TB) remains one of the leading causes of mortality worldwide, exacerbated by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains. In the pursuit of novel therapeutic strategies, thiazolidin-4-one derivatives have gained significant attention due to their structural diversity and broad-spectrum biological activities. This review provides a comprehensive summary of recent advances (2021–present) in the synthesis, structure–activity relationship (SAR), and mechanisms of action of thiazolidin-4-one derivatives as promising antitubercular agents. A detailed discussion of synthetic pathways is presented, including classical and multi-component reactions leading to various subclasses such as thiazolidine-2,4-diones, rhodanines, and pseudothiohydantoins. The SAR analysis highlights key functional groups that enhance antimycobacterial activity, such as halogen substitutions and heterocyclic linkers, while molecular docking and in vitro studies elucidate interactions with key Mtb targets including InhA, MmpL3, and DNA gyrase. Several compounds demonstrate potent inhibitory effects with MIC values lower than or comparable to first-line TB drugs, alongside favorable cytotoxicity profiles. These findings underscore the potential of thiazolidin-4-one scaffolds as a valuable platform for the development of next-generation antitubercular therapeutics. Full article

Background: Extrapulmonary tuberculosis (TB) presents significant diagnostic challenges, particularly in the context of multidrug-resistant (MDR) strains. This study assessed the utility of the WHO-recommended rapid molecular assays, originally validated for pulmonary TB, in diagnosing extrapulmonary TB and detecting the MDR Mycobacterium tuberculosis complex (MTBC). Materials and Methods: A total of 6274 clinical samples, including 4891 pulmonary and 1383 extrapulmonary samples, were analyzed between 2019 and 2022 using the BD MAX™ MDR-TB assay (BD MAX), the Xpert^® MTB/RIF assay (Xpert MTB/RIF), the Xpert^® MTB/XDR assay (Xpert MTB/XDR), FluoroType MTB, and phenotypic drug susceptibility testing (DST). Results: MTBC was detected in 426 samples using BD MAX (376 pulmonary and 50 extrapulmonary), of which 277 were culture-confirmed. Phenotypic testing confirmed 299 positive cultures on Löwenstein–Jensen (LJ) medium and 347 in BD BACTEC™ MGIT™ (BACTEC MGIT) mycobacterial growth indicator tube (BBL) liquid culture. BD MAX showed high sensitivity and specificity for extrapulmonary TB detection (93.1% and 98.4%, respectively). Resistance to isoniazid or rifampicin was identified in 11% of MTBC-positive cases, whereas 3.69% were confirmed as MDR-TB. The molecular assays effectively detected resistance-associated mutations (katG, inhA, and rpoB), with high concordance to phenotypic tests (DST) (κ = 0.69–0.89). Conclusions: This study demonstrates that molecular assays, although validated for pulmonary TB, are also reliable for extrapulmonary TB detection and drug resistance profiling. Their rapid turnaround and robust accuracy support broader implementation in routine diagnostics, especially for challenging extrapulmonary specimens where early detection is critical for targeted therapy. Full article

Tuberculosis (TB) is an infectious disease caused by bacteria that primarily target the lungs. The transmission of this disease occurs through the air in the form of droplet nuclei. Unfortunately, there has been an emergence of resistance to strains of such infections, such as multidrug- as well as extensively drug-resistant strains. Healthcare workers (HCWs) are particularly vulnerable to contracting TB due to their direct contact with patients. This study aims to evaluate the knowledge, attitude, and practices among Lebanese healthcare workers towards TB and its resistant forms, particularly multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). This study is a cross-sectional, descriptive, questionnaire-based research study that was conducted on HCWs in Lebanon. A total of 517 HCWs were included in this study. The findings displayed that 48.52% of HCWs had good knowledge of TB and MDR-TB/XDR-TB, 49.52% had average knowledge, and 2.13% had bad knowledge. Moreover, only 16.25% had a good attitude, 71.92% had an average attitude, and 11.8% had a bad attitude. Furthermore, only 14.7% had good practices, 54.74% had average practices, and 30.56% had bad practices. Having a history of testing for TB was found to be related to increased attitude. Also, the history of having TB-infected family members was found to be linked to both increased attitude and practice scores. Moreover, this study highlights the idea that high knowledge scores do not mean high attitude or high practices scores. On the same note, acceptable attitude scores do not inflict acceptable practice scores. The findings of this study showed that there is an overall good knowledge regarding TB, MDR-TB, and XDR-TB, average attitude, and average-to-bad practices. Gaps are seen in all sectors, even knowledge, especially with matters related to the diagnosis of MDR-TB/XDR-TB and its treatment duration. Also, the attitude section revealed a gap in the understanding of the modes of transmission of such an infection. Full article

Oxazolidinones, novel synthetic antibacterials, inhibit protein biosynthesis and show potent activity against Gram-positive bacteria, including Mycobacterium tuberculosis (MTB). In this study, we aimed to compare the in vitro activity of linezolid (LZD) and four oxazolidinones, including tedizolid (TZD), contezolid (CZD), sutezolid (SZD), and delpazolid (DZD), against multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) isolates from Hainan. We established their epidemiological cut-off values (ECOFFs) using ECOFFinder software and analyzed mutations in rrl (23S rRNA), rplC, rplD, mce3R, tsnR, Rv0545c, Rv0930, Rv3331, and Rv0890c genes to uncover potential mechanisms of oxazolidinone resistance. This study included 177 MTB isolates, comprising 67 MDR and 110 pre-XDR-TB isolates. Overall, SZD exhibited the strongest antibacterial activity against clinical MTB isolates, followed by TZD and LZD, with CZD and DZD showing equivalent but weaker activity (SZD_MIC50 = TZD_MIC50 < LZD_MIC50 < CZD_MIC50 = DZD_MIC50; SZD_MIC90 < TZD_MIC90 = LZD_MIC90 < CZD_MIC90 = DZD_MIC90). Significant differences in MIC distribution were observed for TZD (p < 0.0001), CZD (p < 0.01), SZD (p < 0.0001), and DZD (p < 0.0001) compared to LZD but not between MDR-TB and pre-XDR-TB isolates. We propose the following ECOFFs: SZD, 0.5 µg/mL; LZD, TZD, and CZD, 1.0 µg/mL; DZD, 2.0 µg/mL. No statistically significant differences in resistance rates were observed among these five drugs (p > 0.05). We found that eight MTB isolates (4.52% [8/177]) resisted these five oxazolidinones. Among these, only one isolate, M26, showed an amino acid substitution (Arg79His) in the protein encoded by the rplD gene, which conferred cross-resistance to TZD and CZD. Three distinct mutations were identified in the mce3R gene; notably, isolate P604 displayed two insertions that contributed to resistance against all five oxazolidinones. However, no significant correlation was observed between mutations in the rrl, rplC, rplD, mce3R, tsnR, Rv0545c, Rv0930, Rv3331, and Rv0890c genes with oxazolidinone resistance in the clinical MTB isolates tested. In summary, this study provides the first report on the resistance of MTB in Hainan to the five oxazolidinones (LZD, TZD, CZD, SZD, and DZD). In vitro susceptibility testing indicated that SZD exhibited the strongest antibacterial activity, followed by TZD and LZD, while CZD and DZD demonstrated comparable but weaker effectiveness. Mutations in rplD and mce3R were discovered, but further research is needed to clarify their role in conferring oxazolidinone resistance in MTB. Full article

Extensively drug-resistant tuberculosis (XDR-TB) is a public health concern as drug resistance is outpacing the drug development pipeline. Alternative immunotherapeutic approaches are needed. Peripheral blood mononuclear cells (PBMCs) were isolated from pre-XDR/XDR-TB (n = 25) patients and LTBI (n = 18) participants. Thereafter, monocytic-derived dendritic cells (mo-DCs) were co-cultured with M. tb antigens, with/without a maturation cocktail (interferon-γ, interferon-α, CD40L, IL-1β, and TLR3 and TLR7/8 agonists). Two peptide pools were evaluated: (i) an ECAT peptide pool (ESAT6, CFP10, Ag85B, and TB10.4 peptides) and (ii) a PE/PPE peptide pool. Sonicated lysate of the M. tb HN878 strain served as a control. Mo-DCs were assessed for DC maturation markers, Th1 cytokines, and the ability of the DC-primed PBMCs to restrict the growth of M. tb-infected monocyte-derived macrophages. In pre-XDR/XDR-TB, mo-DCs matured with M. tb antigens (ECAT or PE/PPE peptide pool, or HN878 lysate) + cocktail, compared to mo-DCs matured with M. tb antigens only, showed higher upregulation of co-stimulatory molecules and IL-12p70 (p < 0.001 for both comparisons). The matured mo-DCs had enhanced antigen-specific CD8⁺ T-cell responses to ESAT-6 (p = 0.05) and Ag85B (p = 0.03). Containment was higher with mo-DCs matured with the PE/PPE peptide pool cocktail versus mo-DCs matured with the PE/PPE peptide pool (p = 0.0002). Mo-DCs matured with the PE/PPE peptide pool + cocktail achieved better containment than the ECAT peptide pool + cocktail [50%, (IQR:39–75) versus 46%, (IQR:15–62); p = 0.02]. In patients with pre-XDR/XDR-TB, an effector response primed by mo-DCs matured with an ECAT or PE/PPE peptide pool + cocktail was capable of restricting the growth of M. tb in vitro. Full article

Background: Tuberculosis (TB) is the second leading cause of death from infectious diseases, with 10.6 million cases and 1.3 million deaths. Conventional treatment faces difficulties due to the emergence of resistant strains, such as MDR and XDR-TB. M. tuberculosis uses host cholesterol as an energy source, via the CYP125A1 protein, which catalyses cholesterol oxidation, a process critical for the survival of the bacterium. Methods: This study used computational methods to identify selective inhibitors of the CYP125A1 enzyme. A total of 5968 structure-like compounds from the ASINEX database were evaluated for protein-binding affinity. In addition, docking tests were performed to verify whether the identified compounds could interact with other M. tuberculosis proteins, such as InhA and the human CYP3A4 protein to assess possible off-target effects. Results: The top ten compounds showed a good pharmacological profile and favourable binding energies. Compounds LAS 52160899 and LAS 7298627 served as a basis to search for others with known biological activity, with DB07463 and DB01081 selected as candidates. Conclusions: Potential new inhibitors of the CYP125A1 enzyme were identified. These findings highlight the importance of further research to develop new treatments against M. tuberculosis, especially to combat resistant strains. Full article

Ototoxicity is a significant adverse effect associated with second-line anti-tuberculosis (TB) medications, particularly in treating extensively drug-resistant TB (XDR-TB). This study investigated the awareness of ototoxic effects among adults with XDR-TB undergoing treatment in South Africa, specifically exploring the role of information counselling on ototoxic symptoms, the timing of counselling, the content covered, and the management pathways available. This cross-sectional, descriptive qualitative study was conducted at Brooklyn Chest Hospital in the Western Cape. Ten adults with XDR-TB were purposively sampled and participated in semi-structured in-depth interviews. Data were thematically analyzed and the results revealed variability in information counselling on ototoxicity, with only 30% of participants receiving comprehensive counselling that specifically addressed ototoxic symptoms. The timing of counselling was inconsistent: while 70% of participants received some information before treatment, the remainder received counselling only after treatment initiation, which may have impacted early symptom recognition. Participants’ awareness of ototoxic symptoms was generally limited, with most identifying hearing loss but few recognizing other symptoms such as tinnitus or dizziness. Furthermore, only 20% of participants were provided with clear referral pathways for symptom management. These findings highlight a gap in the depth, timing, and specificity of information counselling on ototoxic effects for XDR-TB in this context. Several interventions can be implemented to address this gap. Full article

Background/Objectives: Tuberculosis (TB) is preventable and curable, but multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose significant challenges worldwide due to the limited treatment options, lengths of therapies, and high rates of treatment failure. The management of MDR-TB has been revolutionized by all oral anti-TB drug regimens that are likely to improve adherence and treatment outcomes. These regimes include bedaquiline (B), pretomanid (P), and linezolid (L) (BPaL), and moxifloxacin if resistance to fluoroquinolones is not detected (BPaLM). Based on the evidence generated by the TB-PRACTECAL and ZeNix randomized controlled trials, BPaL/BPaLM regimens are recommended over the currently recommended longer regimens in patients with MDR-TB or monoresistance to rifampin (RR). To our knowledge, no data are currently available on the implementation of BPaL/BPaLM regimens in Italy. Results: Seventeen patients completed the BPaL/BPaLM regimen, with a treatment success rate of 90% (17/19), consistent with the literature data. Eleven patients out of the nineteen retained in care (58%) complained about symptoms consistent with adverse events (AEs). No treatment interruption was necessary due to AEs. Methods: Here, we report the real-world experience of a tertiary referral hospital for TB in Italy, from 2022 to 2024, in the management, outcomes, and adverse drug reactions of a cohort of twenty-two MDR/RR patients treated with BPaL and BPaLM regimens. Conclusions: BPaL-containing regimens also serve as promising options for patients with RR/MDR-TB in terms of real-life experience, but further multicentric studies are required in Europe to confirm the efficacy of shorter regimens to eliminate MDR TB. Full article

Background: The global push to eliminate tuberculosis (TB) as a public health threat is increasingly urgent, particularly in high-burden areas like the Oliver Reginald Tambo District Municipality, South Africa. Drug-resistant TB (DR-TB) poses a significant challenge to TB control efforts and is a leading cause of TB-related deaths. This study aimed to assess DR-TB transmission patterns and predict future cases using geospatial and predictive modeling techniques. Methods: A retrospective cross-sectional study was conducted across five decentralized DR-TB facilities in the O.R. Tambo District Municipality from January 2018 to December 2020. Data were obtained from Statistics South Africa, and patient GPS coordinates were used to identify clusters of DR-TB cases via DBSCAN clustering. Hotspot analysis (Getis-Ord Gi) was performed, and two predictive models (Linear Regression and Random Forest) were developed to estimate future DR-TB cases. Analyses were conducted using Python 3.8 and R 4.1.1, with significance set at p < 0.05. Results: A total of 456 patients with DR-TB were enrolled, with 56.1% males and 43.9% females. The mean age was 37.5 (±14.9) years. The incidence of DR-TB was 11.89 cases per 100,000 population, with males being disproportionately affected. Key risk factors included poverty, lack of education, and occupational exposure. The DR-TB types included RR-TB (60%), MDR-TB (30%), Pre-XDR-TB (5%), XDR-TB (3%), and INHR-TB (2%). Spatial analysis revealed significant clustering in socio-economically disadvantaged areas. A major cluster was identified, along with a distinct outlier. The analyses of DR-TB case trends using historical data (2018–2021) and projections (2022–2026) from Linear Regression and Random Forest models reveal historical data with a sharp decline in DR-TB case, from 186 in 2018 to 15 in 2021, highlighting substantial progress. The Linear Regression model predicts a continued decline to zero cases by 2026, with an R² = 0.865, a mean squared error (MSE) of 507.175, and a mean absolute error (MAE) of 18.65. Conversely, the Random Forest model forecasts stabilization to around 30–50 cases annually after 2021, achieving an R² = 0.882, an MSE of 443.226, and an MAE of 19.03. These models underscore the importance of adaptive strategies to sustain progress and avoid plateauing in DR-TB reduction efforts. Conclusions: This study highlights the need for targeted interventions in vulnerable populations to curb DR-TB transmission and improve treatment outcomes. Full article

This study investigated the characteristics and outcomes of drug-resistant tuberculosis patients in selected rural healthcare facilities in the Eastern Cape, South Africa. A retrospective review of clinical records from 456 patients, covering the period from January 2018 to December 2020, revealed a statistically significant relationship between DR-TB types and age groups (Chi-square statistic: 30.74, p-value: 0.015). Younger adults (19–35 years) and middle-aged adults (36–50 years) are more frequently affected by RR-TB and MDR-TB, which are the most prevalent forms of DR-TB. Less common types, including Pre-XDR, XDR, and INH TB, were observed in smaller numbers. The study suggests that DR-TB imposes a heavy burden on the working age population. Gender analysis shows that while the frequency of DR-TB differs between males and females, the percentage distribution of DR-TB types is relatively equal. Both genders are predominantly affected by RR-TB and MDR-TB, which together account for nearly 90% of cases. Pre-XDR, XDR, and INH-resistant TB are much less common, comprising only a small percentage of cases in both males and females. High-risk behaviors such as smoking and drinking are linked to a wider diversity of DR-TB types, while occupations like mining and prison work show higher rates of RR-TB and MDR-TB. In HIV-positive individuals, DR-TB is more common, but the distribution of DR-TB types between HIV-positive and negative groups shows no statistically significant difference. However, HIV-positive individuals have a 20% lower survival rate (65%) compared to HIV-negative patients (85%). Financial stability and comorbidities also significantly influence outcomes, with patients having stable income and fewer high-risk comorbidities experiencing better survival and treatment outcomes. The findings underscore the importance of addressing socioeconomic disparities and strengthening healthcare infrastructure to improve DR-TB treatment outcomes in rural Eastern Cape. Full article