Search Results (84)

Excess mortality due to heat is a major public health concern globally. In this study, we investigated the association between extreme heat and mortality in three distinct locations in São Paulo state, Brazil—São Paulo city (the capital), Campinas (a large countryside city), and Marília (a typical medium-sized rural city)—from 2004 to 2018. We applied a generalized linear model (GLM) with a Poisson distribution and a logarithmic link function for each city, using the excess heat factor (EHF) as the exposure metric. The results showed that increases in the EHF were associated with relative risks of 1.0018 (95% CI: 1.0015–1.0022) in São Paulo, 1.0029 (95% CI: 1.0023–1.0036) in Campinas, and 1.0033 (95% CI: 1.0025–1.0041) in Marília. Altogether, 2319 heat-attributable deaths were estimated, representing an economic burden of USD 6.03 billion based on the value of a statistical life. By integrating economic valuation with mortality risk estimates, our study offers a broader perspective on the consequences of extreme heat, reinforcing the need for public health and policy interventions. Full article

(1) Background: The larvae of Dioryctria sylvestrella typically bore into the shoots and cones of Pinus koraiensis, increasing tree breakage risk and reducing cone yield. (2) Methods: Five Beauveria bassiana strains were evaluated for virulence against fourth-instar larvae. And the levels of T-AOC and MDA in the larvae infected by each strain were measured. To assess larval responses to different strains, we measured the activities of six enzymes (SOD, CAT, POD, PPO, CarE, GST) and the levels of GSH and H₂O₂ in larvae treated with each strain. Additionally, the infection process of highly pathogenic B. bassiana in larvae was explored using scanning electron microscopy (SEM). (3) Results: Strain CGMCC3.2055 demonstrated the highest toxicity to larvae, achieving a cumulative corrected mortality of 80.56% on the 4th day and an LT₅₀ of 3.248 days. The T-AOC of larvae treated with strain CGMCC3.2055 was inhibited within 48 h. The relative MDA content in this group was significantly higher than that in other strain-treated groups at 6, 12, and 24 h. In Bb01-treated larvae, H₂O₂ accumulation at 6 and 24 h post-infection was influenced by POD activity rather than GSH levels; in BbZ1-treated larvae, the activities of CAT and POD were upregulated at 6 and 36 h, while the activity of SOD was downregulated, but the content of H₂O₂ increased significantly, resulting in accumulation; in CFCC81428-treated larvae, a decline in T-AOC coincided with substantial H₂O₂ accumulation over 48 h, while a concomitant increase in GSH content bolstered tolerance to lethal oxidative damage; in CGMCC3.2055-treated larvae, H₂O₂ only accumulated significantly at 24 and 48 h, yet upregulated CAT and POD were insufficient to effectively scavenge the excess H₂O₂; and in bio-21738-treated larvae, SOD-driven dismutation generated substantial H₂O₂ from 12 to 48 h, leading to pronounced accumulation from 6 to 48 h, yet limited upregulation of POD (only at 6 and 12 h) and CAT (only at 12 and 48 h) were insufficient to mitigate H₂O₂ buildup. PPO activity was upregulated within 48 h in all treatment groups except for BbZ1, where no upregulation was observed at 12 and 48 h. GST activity was upregulated in all treatment groups except for CGMCC3.2055, where a downregulation was observed at 12 h post-infection. CarE activity was significantly upregulated within 48 h in both CFCC81428 and CGMCC3.2055 groups; in the Bb01 group, CarE was upregulated only at 6 and 48 h; in the BbZ1 group, CarE was downregulated only at 48 h; and in the bio-21738 group, CarE showed no upregulation at 24 and 48 h. Through SEM, the infection process of the strain CGMCC3.2055 on the surface of the larvae was further determined, which mainly included adhesion, the appearance of bud-like protrusions, the growth of germ tubes along the epidermis and penetration of the epidermis, as well as the colonization of the strain and its emergence from the surface of the larvae. (4) Conclusions: This study first screened the highly pathogenic B. bassiana strain CGMCC3.2055 by evaluating its virulence to larvae and post-infection T-AOC and MDA levels. It also clarified the strain’s infection process and the larvae’s immune responses to various strains. Full article

Background: Dietary factors, such as vegetable, fruit, and red meat consumption, have varying effects on the disease burden of diabetes, the world’s third leading health concern. This study aims to evaluate the global impact of vegetable/fruit/red meat consumption on disease burdens. Methods: Diabetes disease burden, vegetable/fruit/red meat consumption, and covariates data were obtained from the Global Burden of Disease Study (GBD) 2021, Food and Agriculture Organization (FAO), and WHO, respectively, and matched by country/region and year. Global vector maps assessed the status of diabetes disease burden and the consumption of three dietary factors in 2021, and their trends from 2010 to 2021 were illustrated through local regression curves. Generalized additive mixed models (GAMMs) were used to analyze relationships, with weights assigned based on log-transformed values relative to the mean population of each country. Results: A comprehensive dataset spanning 2010–2021, encompassing 175 countries/regions, was successfully matched and utilized in the analysis. In 2021, Oceania had the highest diabetes burden, whereas East Asia had a lower one. Globally, the disease burden increased from 2010 to 2021, accompanied by rising per capita vegetable and fruit consumption but declining red meat consumption. Vegetable consumption was inversely correlated with the age-standardized incidence rate (ASIR) and exhibited a “J-shaped” curve with the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year (DALY) rate (ASDR) (nadir at approximately 80 kcal/capita/day (kcal/cap/day). Fruit consumption had a “U-shaped” relationship with ASDR (nadir at approximately 100 kcal/cap/day). Red meat consumption was negatively correlated to ASIR and had a “U-shaped” relationship with ASMR and ASDR (nadir at 200 kcal/cap/day). Conclusions: The global diabetes disease burden is heavy, and dietary consumption varies widely. Vegetable-related risks differ between diabetics and non-diabetics. Proper fruit consumption decreases ASDR. Moderate red meat increases can reduce the disease burden, but excessive consumption increases ASMR and ASDR. Full article

Janus kinase inhibitors (JAKis) represent a relatively new class of immunomodulatory drugs with potent effects on various cytokine signalling pathways. They have revolutionized the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. However, their ability to modulate immune responses presents a dual-edged nature, influencing both protective immunity and pathological inflammation. This review explores the complex role of JAKis in infectious settings, highlighting both beneficial and detrimental effects. On the one hand, experimental models suggest that JAK inhibition can impair host defence mechanisms, increasing susceptibility to certain bacterial and viral infections. For example, tofacitinib-treated mice exhibited more severe joint erosions in Staphylococcus aureus (S. aureus) septic arthritis and showed impaired viral clearance in herpes simplex encephalitis. Additionally, clinical data confirm an increased risk of herpes zoster in patients receiving JAKis, underscoring the need for rigorous monitoring. On the other hand, JAK inhibition has demonstrated protective effects in certain infectious and hyperinflammatory conditions. In sepsis models, including cecal ligation and puncture (CLP) and S. aureus bacteraemia, tofacitinib improved survival by attenuating excessive inflammation. Furthermore, JAKis, particularly baricitinib, have shown substantial efficacy in mitigating cytokine storms during severe COVID-19 infections, leading to improved clinical outcomes and reduced mortality. These observations suggest that JAKis have a role in modulating hyperinflammatory responses in select infectious contexts. In conclusion, JAKis present a complex interplay between immunosuppression and immunomodulation. While they increase the risk of certain infections, they also show potential in managing hyperinflammatory conditions such as cytokine storms. The key challenge is determining which patients and situations benefit most from JAKis while minimizing risks, requiring a careful and personalized treatment approach. Full article

The extensive utilization of nano-zero-valent iron (nZVI) and its engineered derivatives has prompted significant environmental concerns, particularly regarding their phytotoxicological impacts, which remain inadequately characterized. This investigation systematically evaluated the phytotoxicological responses induced by nZVI, Chlorella vulgaris biochar (BC), and Chlorella vulgaris biochar loaded with nano-zero-valent iron (BC/nZVI) on mung bean seed germination and subsequent seedling development. The experimental data revealed that both the nZVI and BC/nZVI treatments significantly suppressed the germination indices, including germination rate, radicle and plumule elongation, and biomass accumulation, with nZVI demonstrating the most pronounced inhibitory effects. During the vegetative growth phases, nZVI exposure substantially impaired plant morphogenesis, manifested through reduced vertical growth, diminished fresh and dry biomass production, and the onset of premature foliar chlorosis, necrosis, desiccation, and, ultimately, plant mortality. A comparative analysis indicated that the BC/nZVI composites exhibited less severe photosynthetic inhibition relative to pristine nZVI. Biochemical assays demonstrated that nZVI exposure elicited the substantial upregulation in antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), concomitant with abnormal ferric ion accumulation in root tissues. Notably, BC/nZVI composites demonstrated the partial mitigation of these physiological disturbances. These empirical findings underscore that excessive iron bioavailability from nZVI induces substantial phytotoxicological stress, while BC matrix incorporation provides the partial amelioration of these adverse effects on seedling ontogeny. Full article

Background: Lower socioeconomic status (SES) has been associated with increased mortality from coronary heart disease. This excess risk, relative to affluent patients, may be due to a combination of more adverse cardiovascular-risk factors, inequalities in access to cardiac investigations, longer waiting times for cardiac revascularisation and lower use of secondary prevention drugs. We sought to investigate whether socio-economic status influenced long-term all-cause mortality after PCI in a large metropolitan city (London), which serves a population of 11 million people with a mixed social background over a 10-year period. Methods: We conducted an observational cohort study of 123,780 consecutive PCI procedures from the Pan-London (United Kingdom) PCI registry. This data set is collected prospectively and includes all patients treated between January 2005 and December 2015. The database includes PCI performed for stable angina and ACS (ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina). Patient socio-economic status was defined by the English Index of Multiple Deprivation (IMD) score, according to residential postcode. Patients were analysed by quintile of IMD score (Q1, least deprived; Q5, most deprived). Median follow-up was 3.7 (IQR: 2.0–5.1) years and the primary outcome was all-cause mortality. Results: The mean age of the patients was 64.3 ± 12.1 years and 25.2% were female. A total of 22.4% of patients were diabetic and 27.3% had a history of previous myocardial infarction. The rates of long-term all-cause mortality increased progressively across quintiles of IMD score, with patients in Q5 showing significantly higher long-term mortality rates compared with patients in Q1 (p = 0.0044). This persisted following the inclusion of a propensity score in the proportional hazard model as a covariate (HR for Q5 compared to Q1: 1.15 [95% CI: 1.10–1.42]). Conclusions: This study has demonstrated that low SES is an independent predictor of adverse clinical outcomes following PCI in the large, diverse metropolitan city of London. There clearly are inequalities in cardio-vascular risk factors, time to access to medical treatment/PCI, access to complex imaging and devices during PCI, access to secondary prevention after PCI, and even race differences. Hence, attention to reducing the burden of cardiovascular risk factors and improving primary prevention, particularly in patients with lower SES, is required. Full article

Background: The association between essential tremor (ET) and mortality risk remains uncertain. This study investigated the impact of episodic memory performance, measured through a word recall task, on mortality risk in ET within the Neurological Disorders in Central Spain (NEDICES) cohort, a population-based study of older adults. Methods: Participants were followed until death or 31 December 2017, and divided into four groups based on ET status and memory performance (errors in the 37-Minimental Examination’s three-word recall task). Cox proportional hazards models estimated mortality hazard ratios (HRs), and the Relative Excess Risk due to Interaction (RERI) assessed additive interactions. Results: Among 3998 participants, 3432 (85.8%) died over a median follow-up of 11.2 years. ET patients with episodic memory impairments had a higher mortality risk (HR = 1.25, 95% CI: 1.06–1.46) compared with controls with similar deficits (HR = 1.19, 95% CI: 1.09–1.28), whereas no significant increase was observed for ET patients without memory impairments (HR = 0.95, 95% CI: 0.74–1.21). RERI analysis revealed no significant additive interaction between ET and memory impairment (fully adjusted RERI: 0.11 [95% CI: −0.19–0.41]). Episodic memory impairments, regardless of ET status, were strongly associated with Alzheimer’s disease as a primary cause of death. Conclusions: These findings highlight the independent contribution of episodic memory impairment to increased mortality risk, with ET modestly amplifying this effect without significant interaction. Further research is needed to explore shared pathophysiological mechanisms between ET and neurodegenerative conditions. Full article

Background: Surgical resection for ampullary lesions lacks clear guidelines. Pancreaticoduodenectomy (PD) is the standard treatment for malignant ampullary tumors but is often excessive for ampullary adenomas (AAs) due to its high morbidity and mortality. Transduodenal ampullectomy (TDA) is generally reserved for small benign lesions where endoscopic treatment fails, but its role in early ampullary cancers is debatable. This study presents our 25-year outcomes with TDA for benign ampullary tumors. Methods: We conducted a retrospective cohort study with prospectively collected data from patients with benign ampullary lesions who underwent TDA between January 1996 and November 2023. Primary outcomes were the 30-day overall and severe (Clavien–Dindo ≥ IIIa) morbidity rates and the 90-day mortality rate. Categoric variables were presented as absolute and relative frequencies, and quantitative variables were presented as means (standard deviation, SD) or medians (range or interquartile range, IQR). Results: Fifty-three patients (29 male; mean [SD] age 62.5 [14.6] years) underwent TDA. The 30-day morbidity rate was 32.1% (17/53 patients), with five (9.4%) cases being severe. The 90-day mortality rate was 1.9%. Definitive histopathology identified 38 (71.7%) AAs and five (9.4%) infiltrating ampullary adenocarcinomas, two (40.0%) of which required subsequent PD. Six (11.3%) patients experienced recurrence. Overall, nine (16.9%) patients died. Conclusions: TDA is a safe and effective technique with acceptable morbidity for non-infiltrating lesions, especially in patients with poor clinical status. Choosing between TDA and PD depends on tumor size, dysplasia grade, and institutional expertise. Lifelong endoscopic surveillance post-TDA is essential for timely recurrence detection. Full article

Portugal is the country in Europe where the death rate in winter and summer has the highest correlation with outdoor temperatures. The Portuguese National Institute of Public Health Ricardo Jorge has developed a national warning system for heat waves called ICARO, which has been in place since 1999 (and is the oldest in Europe). However, it presents some limitations, namely, the low spatial resolution (five regions in Portugal’s mainland), the low temporal forecasting period (one day), and the fact that it was only accessible to health authorities until very recently. This work describes the development of a new public dashboard that uses a new early warning index for extreme weather events, the CLIMAEXTREMO index, which extends the current warning system by improving the current forecasting models for risk by integrating new sources of public data and increasing the spatial and time resolution of the warnings to the municipality or the parish level. The new index is a combination of a new model to estimate the relative mortality increase (updating the model used in ICARO) together with a model of the indoor temperature of building archetypes for all municipalities and a vulnerability index that considers socio-demographic economic indicators. This work discusses the results of the new risk indicator for the heat waves that occurred in Portugal at the end of June and mid-August 2023, and it shows that the index was able to indicate a high risk for the municipalities that had an increase in the number of deaths during that period. Full article

Background: To date, only a few population-representative studies have been carried out on the rare Merkel cell carcinoma (MCC). We provide incidence and survival estimates of MCC, including the conditional relative survival. Methods: We analyzed data from the cancer registry of North Rhine-Westphalia, Germany, 2008–2021, covering a population of 18 million. We included all newly diagnosed MCCs and calculated age-standardized (old European Standard population) incidence rates and unconditional and conditional relative survival. Results: Our analysis included 2164 MCC patients. The age-standardized incidence of MCC was 5.2 (men) and 3.8 (women) per million person-years. The 5-year relative survival was 58.8% (men) and 70.7% (women). Survival was lower among men than women in all age–sex groups and was highest for MCC of the upper extremity in both men (68.2%) and women (79.3%). The sex difference in survival is particularly due to the better survival of women with MCC of the head and neck. In terms of survival, the first two years are particularly critical. Conclusions: Our data validate the worse survival among men and highlights a more favorable prognosis for MCCs located on the limbs. The first two years after diagnosis of MCC are the years with the highest excess mortality. Full article

Background: Studies have reported higher in-hospital mortality rates in patients living with dementia (PlwD) with limited evidence across age groups, clinical departments, and admission diagnoses. The aim of this study was to compare the in-hospital mortality rate of PlwD with patients without dementia across groups, clinical departments, and admission diagnoses. Methods: This case-control study included patients aged ≥ 60 years hospitalized in 1 of 14 German hospitals between January 2019 and July 2023. PlwD were matched to patients without dementia. The associations between dementia and in-hospital mortality across groups were assessed using univariable logistic regression analyses. Results: 15,956 patients with and 15,956 without dementia were included (mean age: 83.9 years, 60.7% female). PlwD had a significantly higher in-hospital mortality rate (14.0% vs. 11.7%; OR 1.24, 95% CI: 1.16–1.32) than non-dementia controls. The highest excess mortality rate was observed in the youngest age group (60–70 years: 10.9% vs. 5.7%; OR: 2.05, 95% CI: 1.30–3.24), decreased with age, and became non-significant in the oldest age group (≥90 years: 16.2% vs. 17.3%; OR: 0.93, 95% CI: 0.80–1.08). Significant differences were found for digestive system disorders (OR: 1.59; 95% CI: 1.15–1.89), cardiovascular and cerebrovascular disorders (OR: 1.51; 95% CI: 1.30–1.75), endocrine, nutritional, and metabolic diseases (OR: 1.42; 95% CI: 1.06–1.90), and pneumonia (OR: 1.20; 95% CI: 1.04–1.37), as well as for all clinic departments except for geriatric departments. Conclusion: The excess mortality rate was highest in younger age groups, where the general mortality and complication rate is relatively low in the general population. Appropriate approaches are needed, especially in non-geriatric wards. Full article

Background: Limited data exist on the prevalence of myosteatosis (i.e., excess accumulation of fat in skeletal muscles) in hepatocellular carcinoma (HCC) patients, and no systematic review or meta-analysis has been conducted in this context. Methods: We searched for articles published from inception until November 2023 to assess the prevalence of myosteatosis in patients with HCC. Results: Ten studies with 3316 patients focusing on myosteatosis and HCC were included. The overall prevalence of myosteatosis in HCC patients was 50% [95% Confidence Interval (CI): 35–65%]. Using the body mass index-based criteria (two studies), the prevalence was 34%, while gender-based criteria (eight studies) yielded 54% (p = 0.31). In Asian studies (n = 8), the prevalence was 45%, compared to 69% in non-Asian countries (two studies) (p = 0.02). For viral-associated HCC (eight studies), the prevalence was 49%, rising to 65% in non-alcoholic fatty liver disease-associated cases (three studies) and 86% in alcoholic liver disease-associated cases (three studies) (p < 0.01). The prevalence of myosteatosis was higher in Child–Pugh class C (3 studies, 91%) than in A (7 studies, 73%) or B (6 studies, 50%) (p = 0.02), but with no difference between Barcelona Clinic Liver Cancer stage A (3 studies, 66%), B (4 studies, 44%) and C (3 studies, 62%) (p = 0.80). Patients with myosteatosis had a significantly higher mortality (six studies) (Relative Risk: 1.35 (95%CI: 1.13–1.62, p < 0.01). Conclusion: The prevalence of myosteatosis is high in HCC patients and is associated with more severe liver disease and higher mortality rates. Full article

Purpose: Racial disparities in infant mortality in the United States persist after adjustment for known confounders of race and mortality association, as well as heterogeneity assessment. Epidemiologic and clinical data continue to show the survival disadvantages of Black/AA children: when Black/AAs are compared to whites, they are three times as likely to die from all-cause mortality. The persistent inability to remove the variance in race–mortality association is partly due to unobserved, unmeasured, and residual confounding, as well as implicit biases in public health and clinical medicine in health equity transformation. This current epidemiologic-perspective explanatory model study aimed to examine the possible explanation of racial differences in U.S. infant mortality using medical misadventures as errors and mistakes, and infants’ involvement in motor vehicular traffic accidents. Materials and Method: Using CDC WONDER ecologic data from 1968 to 2015, we assessed the infant mortality-rate ratio and percent change associated with medical misadventures as well as motor vehicular accidents or trauma. The rate ratio and percent change were estimated using stratification analysis and trend homogeneity, respectively. Results: There was a Black–white racial difference in medical misadventures during the study period. Relative to the years 1968–1978 (rate ratio [RR], 1.43), there was a steady increase in the mortality-rate ratio in 1979–1998 (52%, RR = 1.52), and mortality was more than two times as likely in 1999–2015 (RR = 2.37). However, with respect to motor vehicular accident/trauma mortality, the mortality ratio, although lower among Blacks in 1968–1978 (RR, 0.92), increased in 1979–1998 by 27% (RR = 1.27) but decreased in 1999–2015 (RR, 1.17), though there was still an excess of 17% mortality among Black/AAs. The percent change for medical misadventures indicated an increasing trend from 9.3% in 1998 to 52% in 2015. However, motor vehicular-related mortality indicated a positive trend in 1998 (38.5%) but a negative trend in 2015 (−8.4%). Conclusions: There were substantial race differentials or variances in infant mortality associated with medical misadventures compared to traffic accidents, and Black/AA children relative to whites experienced a survival disadvantage. These comparative findings are suggestive of medical misadventures and motor vehicular trauma as potential explanations for some of the persistent Black–white disparities in overall infant mortality in the U.S. From these findings, we recommend a national effort to address these issues, thus narrowing the observed disparities in the U.S. infant mortality burden among Black/AAs. Full article

This study presents a comprehensive assessment of indoor particulate matter (PM) concentrations, focusing on PM₁, PM_2.5, and PM₁₀ in five primary health centers (PHCs): Arakale (Urban), the Federal College of Agriculture (FECA) (Urban), Iju (semi-urban), Oba-Ile (semi-urban), and Owode (Rural) within Akure local government areas in Nigeria. The primary novelty of this research lies in its detailed exploration of the toxicity potential of these PM fractions, providing valuable insights into the local air quality and associated health risks. This study assesses the health implications by calculating the toxicity potential (TP), relative risk (RR), excess risk (ER), and attributable fractions (Afs) for cardiopulmonary and lung cancer mortality. The results reveal varying RR values for all-cause mortality, with Arakale showing a slight elevation (RR: 1.061), indicating potential health risks. ER values for cardiopulmonary mortality range from 14.728 ± 7.25 to 19.04 ± 0.38, emphasizing the substantial excess risk associated with long-term PM_2.5 exposure. The study also uncovers Afs for cardiopulmonary mortality ranging between 11.03 ± 0.31 and 19.22 ± 0.04, underscoring the significant contribution of PM to cardiovascular and respiratory health risks. Similarly, Afs for lung cancer mortality range from 10.03 ± 0.012 to 17.13 ± 0.10, highlighting the substantial association between PM_2.5 exposure and lung cancer risk. These findings underscore the urgent need for targeted air quality management strategies and public health interventions in the studied locations to mitigate the heightened health risks associated with particulate matter pollution. The calculated RR, ER, and AF values offer crucial insights into the complex relationship between PM exposure and adverse health outcomes, providing a foundation for informed decision-making and future research endeavors. Full article

The injudicious and excessive use of synthetic pesticides has deleterious effects on humans, ecosystems, and biodiversity. As an alternative to traditional crop-protection methods, botanical pesticides are gaining importance. In this research endeavor, we examined the contact toxicity, knockdown time, lethal time, and toxicity horizontal transmission of three natural pesticides from plants (azadirachtin, celangulin, and veratramine) on red imported fire ants (RIFA; Solenopsis invicta). Our research findings indicated that azadirachtin and celangulin exhibited relatively high toxicity, with median lethal dose (LD₅₀) values of 0.200 and 0.046 ng/ant, respectively, whereas veratramine exhibited an LD₅₀ value of 544.610 ng/ant for large workers of S. invicta at 24 h post-treatment. Upon treatment with 0.125 mg/L, the (median lethal time) LT₅₀ values of azadirachtin and celangulin were determined to be 60.410 and 9.905 h, respectively. For veratramine, an LT₅₀ value of 46.967 h was achieved after being tested with 200 mg/L. Remarkably, azadirachtin and celangulin were found to exhibit high horizontal transfer among RIFA, with high secondary mortality (100%) and tertiary mortalities (>61%) after 48 h of treatment with 250 mg/L, as well as with their dust formulations for 72 h. However, veratramine did not exhibit significant toxicity or horizontal transfer effects on RIFA, even at high concentrations. These findings suggest that azadirachtin and celangulin are likely to have a highly prominent potential in the management of S. invicta. Full article