Search Results (48)

The consumption of fresh fruit and vegetables is essential for a healthy diet as they contain a diverse composition of vitamins, minerals, fibre, and bioactive compounds. However, cross-contamination during harvest and post-harvest poses a high risk of microbial contamination. Therefore, handling fruit and vegetables during processing and contact with wet equipment and utensil surfaces is an ideal environment for microbial contamination and foodborne illness. Nevertheless, less attention has been paid to some emerging pathogens that are now increasingly recognised as transmissible to humans through contaminated fruit and vegetables, such as Arcobacter and Cronobacter species in various products, which are the main risk in fruit and vegetables. Cronobacter and Arcobacter spp. are recognised food-safety hazards because they pose a risk of foodborne disease, especially in vulnerable groups such as newborns and immunocompromised individuals. Cronobacter spp. have been linked to severe infant conditions—notably meningitis and sepsis—most often traced to contaminated powdered infant formula. Although Arcobacter spp. have been less extensively studied, they have also been associated with foodborne disease, chiefly from dairy products and meat. With this in mind, this review provides an overview of the main chemical and physical sanitisation methods in terms of their ability to reduce the contamination of fresh fruit and vegetable products caused by two emerging pathogens: Arcobacter and Cronobacter. Emerging chemical (organic acid compounds, extracts, and essential oils) and physical methods (combination of UV-C with electrolysed water, ultrasound, and cold atmospheric plasma) offer innovative and environmentally friendly alternatives to traditional approaches. These methods often utilise natural materials, less toxic solvents, and novel techniques, resulting in more sustainable processes compared with traditional methods that may use harsh chemicals and environmentally harmful processes. This review provides the fruit and vegetable industry with a general overview of possible decontamination alternatives to develop optimal and efficient processes that ensure food safety. Full article

Background: Asymptomatic congenital cytomegalovirus (acCMV) infections represent 85–90% of all congenital CMV infection. The incidence of late-onset sequelae in these cases significantly contribute to the burden of CMV disease. The timing of maternal infection (TMI) has been identified as the main predictor of late-onset sequelae in acCMV infants, and follow-up programs in Europe are currently calibrated according to the TMI. Our aim was to evaluate neonatal viremia as a possible predictor of the TMI in acCMV infections. Methods: Plasma viral loads (PVLs) were assessed in the first month of life in a population of acCMV-infected newborns delivered by women who suffer a primary CMV infection during pregnancy. TMI was assigned to a trimester of pregnancy according to the maternal serological screening. PVLs were evaluated in relation to the TMI and gestational age (GA) at birth. Results: One hundred and ten newborns were, respectively, assigned to preconceptional (6.4%), 1st (27.3%), 2nd (38.2%), and 3rd (28.2%) trimester infections. Median neonatal PVLs values were significantly different between groups (p < 0.001). First-trimester infections exhibited significantly higher PVLs when compared with third-trimester ones (p < 0.001). Overall, PVLs showed an inverse correlation with GA at birth (p = 0.003). Conclusions: Median neonatal PVLs are significantly higher in 1st trimester infections if compared with 3rd trimester ones, but a wide overlap between PVL values prevent their possible use as a predictor of the TMI. In our population, a significant inverse relationship, mainly dependent on 1st and 2nd trimester infections, is demonstrated between PVLs and GA. Overall, fetal viremia is already decreasing weeks before the term of pregnancy. Full article

Background: Patent ductus arteriosus (PDA) in preterm infants presents a significant challenge in neonatal care, marked by ongoing debates about its definition, diagnosis, treatment options, and effects on patient outcomes. Plasma biomarkers assess mediators involved in PDA closure and hemodynamic responses, assisting in identifying newborns at higher risk of developing potentially serious neonatal conditions. The purpose of this review was to investigate the relationship between PDA and various plasma biomarkers used to evaluate and diagnose ductal patency during perinatal life, as outlined in the relevant literature. Methods: We conducted an electronic search of the National Library of Medicine (MEDLINE)/PubMed and Web of Science for relevant studies published up to December 2024, including prospective, retrospective, cohort, and cross-sectional studies, as well as reviews and meta-analyses. The keywords used in the search included “preterm infant”, “persistent ductus arteriosus”, “patent ductus arteriosus”, “PDA”, “neonatal biomarkers”, “cardiac biomarkers”, and “vasoactive biomarkers”. Results: Out of the 813 identified articles, 85 were included in our review of cardiac biomarkers: Natriuretic peptides (NPs), Cardiac troponin T (cTnT), vasoactive biomarkers (Mid-regional pro-adrenomedullin (MR-proADM), Endothelin-1 (ET-1), Copeptin, and Isoprostanes (IPs)), and inflammatory biomarkers (Interleukin-6 (IL-6), IL-8, IL-10, Growth Differentiation Factor 15 (GDF-15), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), Macrophage Inflammatory Protein-1α (MIP-1α/CCL3)) in relation to PDA. Conclusions: Even if research shows a strong correlation between specific biomarkers and echocardiographic parameters in patients with PDA, clinical judgment must take these evaluations into account, particularly when determining whether to treat a PDA. Future research should focus on investigating new biomarkers associated with the underlying mechanisms of perinatal ductus arteriosus dynamics in preterm infants. Full article

Background: In recent years, progress in the field of care has made prematurity an increasingly frequent phenomenon. The premature newborn, due to incompetence, is often subjected to parenteral nutrition (PN) for prolonged periods, and there may be several complications associated with it, first and foremost metabolic complications. Methods: In particular, the aim of this study was to evaluate how specific risk factors and/or auxological parameters influenced plasma variations in calcium, phosphorus, and magnesium levels. This is because, although little analyzed in the past, these electrolytes are essential for limiting the onset of unfavorable outcomes in neonatal age. This retrospective observational study was conducted by accessing the site intranet of the University Hospital “P. Giaccone” of Palermo, recruiting all newborns with PN necessities (106 in a total of 191), admitted to NICU in the period between 1 January 2020 and 1 January 2023. Infants undergoing PN through a central venous catheter (CVC), who remained in situ for a period ≥ 72 h, admitted to the NICU for the first time, were included. Infants with congenital malformations and/or deceased and/or transferred and/or without CVC or with CVC who remained in situ for a period < 72 h were excluded. We thus obtained 35 newborns in 2020, 33 newborns in 2021, and 38 newborns in 2022. Results: Hypophosphatemia was associated with a lower weight percentile (average 34.8 °C vs. 50.8 °C; p = 0.02) and a longer duration of PN (average 34.6 days vs. 17.3 days; p = 0.002). Newborns with hypercalcemia had, on average, lower gestational age (average 31.6 weeks vs. 35.7 weeks; p = 0.049) and weight at birth (average 1586 g vs. 2520 g; p = 0.038). Newborns with hypermagnesemia had, on average, higher weight and length (average weight percentile 62.1 °C vs. 42.7 °C; p = 0.038; average length percentile 66.7 °C vs. 44.4 °C; p = 0.003). Among the risk factors, cesarean section and undergoing surgery most influence the serum trend of the analyzed electrolytes. Conclusions: Although our results are partial and preliminary and have not always reached statistical significance, it is clear that dyselectrolytemias, in the context of metabolic complications PN-related, must be re-evaluated and carefully examined by the clinician. Prospective and controlled trials are needed to confirm our data, i.e., that the “calcium-phosphorus-magnesium axis” no longer plays only the niche role that was previously believed. Full article

Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its impact on neonatal outcomes and respiratory morbidity, as well as the underlying pathogenetic mechanism, has not yet been extensively studied. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for the prevention of respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, microRNA (miRNA) profiling by small RNA deep sequencing and quantitative real-time PCR was performed on 160 blood plasma samples from preterm infants (gestational age: 33–36 weeks) and their mothers who had been diagnosed with or without PAS depending on the timing of the antenatal RDS prophylaxis. A significant increase in hsa-miR-199a-3p and hsa-miR-382-5p levels was observed in the blood plasma of the newborns from mothers with PAS compared to the control group. A clear trend toward the normalization of hsa-miR-199a-3p and hsa-miR-382-5p levels in the neonatal blood plasma of the PAS groups was observed when CT was administered within 14 days before delivery, but not beyond 14 days. Direct correlations were found among the hsa-miR-382-5p level in neonatal blood plasma and the hsa-miR-199a-3p level in the same sample (r = 0.49; p < 0.001), the oxygen requirements in the NICU (r = 0.41; p = 0.001), the duration of the NICU stay (r = 0.31; p = 0.019), and the severity of the newborn’s condition based on the NEOMOD scale (r = 0.36; p = 0.005). Logistic regression models based on the maternal plasma levels of hsa-miR-199a-3p and hsa-miR-382-5p predicted the need for cardiotonic therapy, invasive mechanical ventilation, or high-frequency oscillatory ventilation in newborns during the early neonatal period, with a sensitivity of 95–100%. According to the literary data, these miRNAs regulate fetal organogenesis via IGF-1, the formation of proper lung tissue architecture, surfactant synthesis in alveolar cells, and vascular tone. Full article

There is a growing interest in the composition of amniotic fluid (AF) in both humans and animals. In addition to its nutritional and protective functions for the foetus, current knowledge demonstrates that AF also serves advanced diagnostic, prognostic, and therapeutic roles. Newborn dogs have an underdeveloped immune system, making them highly susceptible to dangerous pathogens such as canine parvovirus (CPV-2), canine infectious hepatitis virus (CAdV-1), and canine distemper virus (CDV), thus exposing them to a high risk of mortality in the first weeks of life. Immunoglobulins G (IgGs) represent the only antibody isotype capable of crossing the placenta in a small amount and have been detected also in canine AF. The primary aim of this study was to investigate the reliability of AF collected at birth as a marker of passive immunity in canine species. For this purpose, total and specific IgGs against CPV-2, CAdV-1, and CDV were investigated and quantified in both maternal plasma and AF collected at the time of caesarean section. The vaccination status of the bitches was also taken into consideration. Since the immune system can be influenced by gestational age, with preterm infants having immature innate and adaptive immunity, IgG concentrations were correlated with amniotic lecithin, sphingomyelin, cortisol, surfactant protein A, and pentraxin 3 levels. In a previous study from our group on foetal maturity these molecules were measured in the same samples. Finally, correlations between their amniotic content and neonatal outcomes were investigated. This study demonstrates that AF analysis at birth can provide valuable insights into neonatal immunity in puppies, offering a non-invasive method to detect potential early health risks, for improved puppy care and management. Full article

Circulating food metabolites could improve dietary assessments by complementing traditional methods. Here, biomarker candidates of food intake were identified in plasma samples from pregnancy (gestational week 29, N = 579), delivery (mothers, N = 532; infants, N = 348), and four months postpartum (mothers, N = 477; breastfed infants, N = 193) and associated to food intake assessed with semi-quantitative food frequency questionnaires. Families from the Swedish birth cohort Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) were included. Samples were analyzed using untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics. Both exposure and outcome were standardized, and relationships were investigated using a linear regression analysis. The intake of fruits and berries and fruit juice were both positively related to proline betaine levels during pregnancy (fruits and berries, β = 0.23, FDR < 0.001; fruit juice, β = 0.27, FDR < 0.001), at delivery (fruit juice, infants: β = 0.19, FDR = 0.028), and postpartum (fruits and berries, mothers: β = 0.27, FDR < 0.001, infants: β = 0.29, FDR < 0.001; fruit juice, mothers: β = 0.37, FDR < 0.001). Lutein levels were positively related to vegetable intake during pregnancy (β = 0.23, FDR < 0.001) and delivery (mothers: β = 0.24, FDR < 0.001; newborns: β = 0.18, FDR = 0.014) and CMPF with fatty fish intake postpartum (mothers: β = 0.20, FDR < 0.001). No clear relationships were observed with the expected food sources of the remaining metabolites (acetylcarnitine, choline, indole-3-lactic acid, pipecolic acid). Our study suggests that plasma lutein could be useful as a more general food group intake biomarker for vegetables and fruits during pregnancy and delivery. Also, our results suggest the application of proline betaine as an intake biomarker of citrus fruit during gestation and lactation. Full article

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications. Full article

Significant risk of side effects of drug therapy in newborns, especially in premature neonates, is associated with immaturity of a number of enzyme systems and biotransformation mechanisms and pharmacokinetic specificity. We consider the use of thiotriazoline), a drug licensed in Ukraine with proven hepatoprotective and cardioprotective activity and a high safety profile, for premature infants to reduce side effects of antibiotic therapy. The use of thiotriazoline in antibiotic therapy results in an increase in the concentration of eNOS in blood plasma and a decrease in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and bilirubin in blood plasma. These results provide experimental support for the use of thiotriazoline to reduce the side effects of azithromycin therapy in newborns. Full article

An important role in the network of interconnections between the mother and child is played by adipokines, which are adipose tissue hormones engaged in the regulation of metabolism. Alternations of maternal adipokines translate to the worsening of maternal insulin resistance as well as metabolic stress, altered placenta functions, and fetal development, which finally contribute to long-term metabolic unfavorable conditions. This paper is the first to summarize the current state of knowledge concerning the concentrations of individual adipokines in different biological fluids of maternal and cord plasma, newborn/infant plasma, milk, and the placenta, where it highlights the impact of adverse perinatal risk factors, including gestational diabetes mellitus, preeclampsia, intrauterine growth restriction, preterm delivery, and maternal obesity on the adipokine patterns in maternal–infant dyads. The importance of adipokine measurement and relationships in biological fluids during pregnancy and lactation is crucial for public health in the area of prevention of most diet-related metabolic diseases. The review highlights the huge knowledge gap in the field of hormones participating in the energy homeostasis and metabolic pathways during perinatal and postnatal periods in the mother–child dyad. An in-depth characterization is needed to confirm if the adverse outcomes of early developmental programming might be modulated via maternal lifestyle intervention. Full article

The aim of this study was to evaluate the intensity of oxidative stress by measuring the concentrations of lipid peroxidation products (LPO) in fetal membrane, umbilical cord, and placenta samples obtained from women with multiple pregnancies. Additionally, the effectiveness of protection against oxidative stress was assessed by measuring the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR). Due to the role of iron (Fe), copper (Cu), and zinc (Zn) as cofactors for antioxidant enzymes, the concentrations of these elements were also analyzed in the studied afterbirths. The obtained data were compared with newborn parameters, selected environmental factors, and the health status of women during pregnancy to determine the relationship between oxidative stress and the health of women and their offspring during pregnancy. The study involved women (n = 22) with multiple pregnancies and their newborns (n = 45). The Fe, Zn, and Cu levels in the placenta, umbilical cord, and fetal membrane were determined using inductively coupled plasma atomic emission spectroscopy (ICP-OES) using an ICAP 7400 Duo system. Commercial assays were used to determine SOD, GPx, GR, CAT, and LPO activity levels. The determinations were made spectrophotometrically. The present study also investigated the relationships between trace element concentrations in fetal membrane, placenta, and umbilical cord samples and various maternal and infant parameters in women. Notably, a strong positive correlation was observed between Cu and Zn concentrations in the fetal membrane (p = 0.66) and between Zn and Fe concentrations in the placenta (p = 0.61). The fetal membrane Zn concentration exhibited a negative correlation with shoulder width (p = −0.35), while the placenta Cu concentration was positively correlated with placenta weight (p = 0.46) and shoulder width (p = 0.36). The umbilical cord Cu level was positively correlated with head circumference (p = 0.36) and birth weight (p = 0.35), while the placenta Fe concentration was positively correlated with placenta weight (p = 0.33). Furthermore, correlations were determined between the parameters of antioxidative stress (GPx, GR, CAT, SOD) and oxidative stress (LPO) and the parameters of infants and maternal characteristics. A negative correlation was observed between Fe and LPO product concentrations in the fetal membrane (p = −0.50) and placenta (p = −0.58), while the Cu concentration positively correlated with SOD activity in the umbilical cord (p = 0.55). Given that multiple pregnancies are associated with various complications, such as preterm birth, gestational hypertension, gestational diabetes, and placental and umbilical cord abnormalities, research in this area is crucial for preventing obstetric failures. Our results could serve as comparative data for future studies. However, we advise caution when interpreting our results, despite achieving statistical significance. Full article

Pre-pregnancy obesity and excessive gestational weight gain (GWG) appear to affect birth weight and the offspring’s risk of obesity and disease later in life. However, the identification of the mediators of this relationship, could be of clinical interest, taking into account the presence of other confounding factors, such as genetics and other shared influences. The aim of this study was to evaluate the metabolomic profiles of infants at birth (cord blood) and 6 and 12 months after birth to identify offspring metabolites associated with maternal GWG. Nuclear Magnetic Resonance (NMR) metabolic profiles were measured in 154 plasma samples from newborns (82 cord blood samples) and in 46 and 26 of these samples at 6 months and 12 months of age, respectively. The levels of relative abundance of 73 metabolomic parameters were determined in all the samples. We performed univariate and machine-learning analysis of the association between the metabolic levels and maternal weight gain adjusted for mother‘s age, Body Mass Index (BMI), diabetes, diet adherence and infant sex. Overall, our results showed differences, both at the univariate level and in the machine-learning models, between the offspring, according to the tertiles of maternal weight gain. Some of these differences were resolved at 6 and 12 months of age, whereas some others remained. Lactate and leucine were the metabolites with the strongest and longest association with maternal weight gain during pregnancy. Leucine, as well as other significant metabolites, have been associated in the past with metabolic wellness in both general and obese populations. Our results suggest that the metabolic changes associated to excessive GWG are present in children from early life. Full article

Background: Neonates may require higher doses of micafungin than adults to reach the therapeutic effect for increased plasma clearance. Only poor and inconclusive data are available still now to support this hypothesis, especially with regard to central nervous system micafungin concentrations. To assess the pharmacokinetics of increased doses (8 to 15 mg/kg/day) of micafungin in preterm and term neonates with invasive candidiasis and to complete previously presented results, we analyzed the pharmacokinetic data on a total of 53 newborns treated with micafungin, whereby 3 of them had Candida meningitis and hydrocephalus. Methods: Fifty-three neonates with systemic candidiasis, three of them with meningitis, were treated for at least 14 days with intravenous micafungin (Mycamine^®) at a dosage ranging from 8 to 15 mg/kg/day. Plasma and cerebrospinal fluid (CSF) concentrations of micafungin were measured before the drug administration and at 1, 2, and 8 h after the end of the infusion using high-performance liquid chromatography (HPLC). Systemic exposure was assessed according to AUC_0–24, plasma clearance (CL), and half-life measured in 52/53 patients, divided by chronological age. Results and conclusions: The mean micafungin clearance is higher in neonates than in older infants (0.036 L/h/kg before 28 days of life versus 0.028 L/h/kg after 120 days). The drug half-life is shorter in neonates than in older patients (13.5 h before 28 days of life versus 14.4 h after 120 days). With doses ranging between 8 and 15 mg/kg/day, micafungin crosses the blood–brain barrier reaching therapeutic levels in CSF. Full article

Surgery is frequently associated with excessive oxidative stress. Melatonin acts as an antioxidant and transient melatonin deficiency has been described in neonatal surgical patients. This randomized, blinded, prospective pilot study tested the hypothesis that oral melatonin supplementation in newborn infants undergoing surgery is effective in reducing perioperative oxidative stress. A total of twenty-three newborn infants requiring surgery were enrolled: 10 received a single dose of oral melatonin 0.5 mg/kg in the morning, before surgery (MEL group), and 13 newborns served as the control group (untreated group). Plasma concentrations of melatonin, Non-Protein-Bound Iron (NPBI), Advanced Oxidation Protein Products (AOPP), and F2-Isoprostanes (F2-IsoPs) were measured. Both in the pre- and postoperative period, melatonin concentrations were significantly higher in the MEL group than in the untreated group (preoperative: 1265.50 ± 717.03 vs. 23.23 ± 17.71 pg/mL, p < 0.0001; postoperative: 1465.20 ± 538.38 vs. 56.47 ± 37.18 pg/mL, p < 0.0001). Melatonin significantly increased from the pre- to postoperative period in the untreated group (23.23 ± 17.71 vs. 56.47 ± 37.18 pg/mL; pg/mL p = 0.006). In the MEL group, the mean blood concentrations of NPBI, F2-IsoPs, and AOPP significantly decreased from the pre- to the postoperative period (4.69 ± 3.85 vs. 1.65 ± 1.18 micromol/dL, p = 0.049; 128.40 ± 92.30 vs. 50.25 ± 47.47 pg/mL, p = 0.037 and 65.18 ± 15.50 vs. 43.98 ± 17.92 micromol/dL, p = 0.022, respectively). Melatonin concentration increases physiologically from the pre- to the postoperative period, suggesting a defensive physiologic response to counteract oxidative stress. The administration of exogenous melatonin in newborn infants undergoing surgery reduces lipid and protein peroxidation in the postoperative period, showing a potential role in protecting babies from the deleterious consequences of oxidative stress. Full article

The prenatal period is critical for auditory development; thus, prenatal influences on auditory development may significantly impact long-term hearing ability. While previous studies identified a protective effect of carotenoids on adult hearing, the impact of these nutrients on hearing outcomes in neonates is not well understood. The purpose of this study is to investigate the relationship between maternal and umbilical cord plasma retinol and carotenoid concentrations and abnormal newborn hearing screen (NHS) results. Mother–infant dyads (n = 546) were enrolled at delivery. Plasma samples were analyzed using HPLC and LC–MS/MS. NHS results were obtained from medical records. Statistical analysis utilized Mann–Whitney U tests and logistic regression models, with p ≤ 0.05 considered statistically significant. Abnormal NHS results were observed in 8.5% of infants. Higher median cord retinol (187.4 vs. 162.2 μg/L, p = 0.01), maternal trans-β-carotene (206.1 vs. 149.4 μg/L, p = 0.02), maternal cis-β-carotene (15.9 vs. 11.2 μg/L, p = 0.02), and cord trans-β-carotene (15.5 vs. 8.0 μg/L, p = 0.04) were associated with abnormal NHS. Significant associations between natural log-transformed retinol and β-carotene concentrations and abnormal NHS results remained after adjustment for smoking status, maternal age, and corrected gestational age. Further studies should investigate if congenital metabolic deficiencies, pesticide contamination of carotenoid-rich foods, maternal hypothyroidism, or other variables mediate this relationship. Full article