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15 pages, 969 KB  
Article
Healthcare-Associated Infections, Antibiotic Use, and Invasive Devices: A Repeated Point Prevalence Survey
by Maria Costantino, Anna Maria Della Corte, Valentina Giudice, Luigi Fortino, Maria Nappo, Giovanni Boccia, Vittoria Satriani, Giuseppe Panzuto, Walter Longanella, Francesco De Caro and Antonella Maisto
Hygiene 2026, 6(2), 34; https://doi.org/10.3390/hygiene6020034 (registering DOI) - 6 Jun 2026
Abstract
Background: Healthcare-associated infections (HAIs) and antimicrobial resistance are major global public health challenges, influenced by patient clinical complexity and prescribing practices. Methods: Three-point prevalence surveys (PPSs) were conducted (P1: November 2024; P2: June 2025; P3: November 2025), involving 456 patients at the University [...] Read more.
Background: Healthcare-associated infections (HAIs) and antimicrobial resistance are major global public health challenges, influenced by patient clinical complexity and prescribing practices. Methods: Three-point prevalence surveys (PPSs) were conducted (P1: November 2024; P2: June 2025; P3: November 2025), involving 456 patients at the University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy. Results: The prevalence of HAIs fluctuated between 3.1% (P1) and a peak of 6.1% (P2), before decreasing to 1.9% (P3), correlating with the presence of multidrug-resistant pathogens in critical care areas. The prevalence of antibiotic use remained stable (~48%), with a decrease in carbapenem use (from 12% to 9%). A decline in ‘unknown’ McCabe scores from 24.6% to 6.8% (p < 0.001) was also observed, suggesting an improvement in completeness of prognostic data, although changes in data collection practices may also have contributed to this change. Conclusions: We showed an association between clinical severity, prolonged hospitalization, invasive device use, and infection risk in a single tertiary-care hospital, within an exploratory, cross-sectional framework. Despite high healthcare pressure, improvements were observed in antimicrobial stewardship and clinical surveillance. Future strategies should focus on optimal device management and on extending surveillance activities to medical wards with increasing patient complexity. Full article
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14 pages, 292 KB  
Review
Endoscopic Ultrasound-Guided Gallbladder Drainage in the Treatment of Acute Cholecystitis and Malignant Biliary Obstruction: A Literature Review
by Xinyue Zhao and Nan Ge
Gastroenterol. Insights 2026, 17(2), 36; https://doi.org/10.3390/gastroent17020036 (registering DOI) - 6 Jun 2026
Abstract
Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an emerging intervention that provides a minimally invasive approach to drainage of the gallbladder, showing promising results in treating acute cholecystitis (AC) and malignant biliary obstruction (MBO). This review summarizes the current applications of EUS-GBD and compares [...] Read more.
Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an emerging intervention that provides a minimally invasive approach to drainage of the gallbladder, showing promising results in treating acute cholecystitis (AC) and malignant biliary obstruction (MBO). This review summarizes the current applications of EUS-GBD and compares its clinical effectiveness with traditional methods such as percutaneous transhepatic gallbladder drainage (PT-GBD) and endoscopic transpapillary gallbladder drainage (ET-GBD). Available evidence suggests that EUS-GBD may offer potential advantages in terms of success rates and complication profiles, particularly in patients who are not candidates for surgery or those at high surgical risk. The method is effective in reducing inflammation, alleviating symptoms from obstruction, and improving patient quality of life. This article also discusses the technical evolution of EUS-GBD, its indications, complications, and its comparative advantages over other drainage techniques. These observations suggest that EUS-GBD may represent a valuable addition to the therapeutic armamentarium for selected high-risk patients. Full article
18 pages, 1160 KB  
Article
Differential Associations of Oxidative Biomarkers with Symptomatic and Systolic Severity in Heart Failure
by Aleksandra Arsić, Bojana Kisić, Vladan Perić, Ivana Stevanović, Ana Savić Radojević, Zoran Bukumirić, Ilija Dragojević, Marija Vasić, Martin Popević, Dragiša Rašić and Snežana Hadžistević
Medicina 2026, 62(6), 1108; https://doi.org/10.3390/medicina62061108 (registering DOI) - 6 Jun 2026
Abstract
Background and Objectives: Oxidative stress is recognized as an important contributor to heart failure (HF) pathophysiology, but the relationships of individual oxidative and antioxidant biomarkers with symptomatic severity and systolic dysfunction remain insufficiently defined. This study examined circulating oxidative and nitrosative stress [...] Read more.
Background and Objectives: Oxidative stress is recognized as an important contributor to heart failure (HF) pathophysiology, but the relationships of individual oxidative and antioxidant biomarkers with symptomatic severity and systolic dysfunction remain insufficiently defined. This study examined circulating oxidative and nitrosative stress markers across New York Heart Association (NYHA) classes and left ventricular ejection fraction (LVEF) categories in HF and their associations with HF severity. Materials and Methods: In this case–control study, 85 patients with HF and 33 healthy controls were included. Malondialdehyde (MDA), nitrates and nitrites (NOx), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), sulfhydryl (SH) groups, and NT-proBNP were measured. Group differences were analyzed using the Kruskal–Wallis test with post hoc comparisons. Adjusted ordinal logistic regression models examined associations with NYHA class and LVEF category, and receiver operating characteristic (ROC) analysis evaluated discriminatory performance. Results: Compared with controls, all biomarkers differed significantly across NYHA classes and LVEF categories (all p < 0.001). In separate adjusted models, higher NOx, MDA, and NT-proBNP were associated with worse NYHA class and more impaired LVEF, whereas higher antioxidant marker levels were associated with lower odds of severe HF. In combined models, NOx remained independently associated with worse NYHA class (OR 1.07, 95% CI 1.04–1.11; p < 0.001), while MDA remained independently associated with more impaired LVEF (OR 1.02, 95% CI 1.00–1.03; p = 0.022). NT-proBNP showed the best discrimination for NYHA III/IV versus I/II (AUC 0.966), while among oxidative biomarkers NOx performed best for symptomatic severity (AUC 0.782) and MDA for LVEF ≤ 40% (AUC 0.751). Conclusions: HF is characterized by increased oxidative and nitrosative stress together with reduced antioxidant defense. NOx appears more closely related to symptomatic severity, whereas MDA appears more closely related to systolic dysfunction. However, NT-proBNP remained the strongest overall discriminator. NOx and MDA may provide complementary mechanistic information on redox imbalance across HF severity categories. Full article
(This article belongs to the Special Issue New Insights into Heart Failure: 2nd Edition)
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14 pages, 425 KB  
Article
Effect of Boswellia serrata on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers—A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Trial
by Sascha Hammer, Marco Reiser, Mathias Bader, Jakob Pannold, Angelika Moser, Maximilian Niederer, Anselm Johannes Schlemmer, Sebastian Labenbacher, Kordula Lang-Illeviech and Helmar Bornemann-Cimenti
Nutrients 2026, 18(12), 1839; https://doi.org/10.3390/nu18121839 (registering DOI) - 6 Jun 2026
Abstract
Background: Boswellia serrata has traditionally been used in Ayurvedic medicine for its anti-inflammatory and antioxidant properties. Although several studies support clinical analgesic efficacy, the underlying mechanisms have not been investigated in human experimental pain models. This randomized, double-blind, placebo-controlled, crossover pilot trial aimed [...] Read more.
Background: Boswellia serrata has traditionally been used in Ayurvedic medicine for its anti-inflammatory and antioxidant properties. Although several studies support clinical analgesic efficacy, the underlying mechanisms have not been investigated in human experimental pain models. This randomized, double-blind, placebo-controlled, crossover pilot trial aimed to examine the mode of action of Boswellia serrata to differentiate between its peripheral and central effects. This exploratory pilot study was designed to generate preliminary effect size estimates and assess functional pain-processing outcomes, rather than to provide definitive evidence of clinical efficacy. Methods: Twelve healthy volunteers were recruited and received either 300 mg of Boswellia serrata extract or a visually identical placebo twice daily for 28 days, separated by a 4-week washout period. Pain and sensitization were induced using a topical capsaicin model. Outcomes included spontaneous pain intensity, mechanical allodynia, pinprick hyperalgesia, thermal thresholds, and conditioned pain modulation, alongside psychological assessments of mood, anxiety, sleep, and structured adverse-event monitoring. Results: Results showed no significant difference in the primary endpoint of spontaneous pain intensity between Boswellia and placebo (VAS 43 ± 21 vs. 47 ± 17; d = 0.18; p = 0.539). Conclusions: While Boswellia serrata did not significantly reduce acute peak pain in this model, the observed trends suggest a potential multi-level modulatory influence on nociceptive processing and endogenous pain inhibition. These findings warrant larger clinical trials to further elucidate its therapeutic potential, particularly in populations with impaired pain modulation. Full article
(This article belongs to the Section Clinical Nutrition)
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22 pages, 15312 KB  
Article
Synthesis of MPB@ZnPc Nanomaterials and Their Application in the Treatment of Periodontitis
by Qingyue Tan, Xuan Zhang, Yujuan Tian and Rui Li
Int. J. Mol. Sci. 2026, 27(12), 5161; https://doi.org/10.3390/ijms27125161 (registering DOI) - 6 Jun 2026
Abstract
Periodontitis treatment remains challenging due to incomplete removal of plaque biofilms, increasing antibiotic resistance, and dysregulated host inflammatory responses. In this study, an MPB@ZnPc nanomaterial was constructed to achieve efficient antibacterial activity through the synergistic effects of photothermal therapy (PTT) and photodynamic therapy [...] Read more.
Periodontitis treatment remains challenging due to incomplete removal of plaque biofilms, increasing antibiotic resistance, and dysregulated host inflammatory responses. In this study, an MPB@ZnPc nanomaterial was constructed to achieve efficient antibacterial activity through the synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), while also exerting immunomodulatory functions under dark conditions. MPB@ZnPc (mesoporous Prussian blue @ zinc phthalocyanine) was synthesized using a polymer-templating method and systematically characterized. The results demonstrated that the nanomaterial exhibited excellent photothermal conversion efficiency and stability under near-infrared (NIR) irradiation. It also showed strong photocatalytic degradation performance toward methylene blue and rhodamine B, accompanied by substantial reactive oxygen species (ROS) generation. In vitro antibacterial assays revealed that MPB@ZnPc achieved significantly enhanced antibacterial efficacy compared with individual components, with bactericidal rates of 99.61 ± 0.52% against Porphyromonas gingivalis and 99.77 ± 0.32% against Fusobacterium nucleatum. The corresponding biofilm removal rates reached 93.60 ± 3.30% and 93.25 ± 3.30%, respectively. Under dark conditions, the nanomaterial exhibited good biocompatibility toward L929 cells and effectively inhibited lipopolysaccharide (LPS)-induced M1 polarization of macrophages, leading to reduced expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Mechanistically, MPB@ZnPc suppressed the activation of the NF-κB signaling pathway. Overall, MPB@ZnPc provides a promising strategy for precise periodontitis treatment by integrating synergistic antibacterial activity with immunomodulatory effects. Full article
(This article belongs to the Section Materials Science)
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13 pages, 358 KB  
Article
Association of Early Albumin Administration with Clinical Outcomes in Patients Hospitalized with Spontaneous Bacterial Peritonitis: A Propensity-Matched Cohort Study
by Noor Albusta, Mohamed Abdulla, Sara Isa and Rehab Almarzooq
Reports 2026, 9(2), 176; https://doi.org/10.3390/reports9020176 (registering DOI) - 6 Jun 2026
Abstract
Background/Objectives: Spontaneous bacterial peritonitis (SBP) is a serious complication of decompensated cirrhosis and is associated with acute kidney injury (AKI), organ failure, and death. Intravenous albumin is recommended in SBP because it reduces renal impairment and mortality, particularly in patients at higher risk [...] Read more.
Background/Objectives: Spontaneous bacterial peritonitis (SBP) is a serious complication of decompensated cirrhosis and is associated with acute kidney injury (AKI), organ failure, and death. Intravenous albumin is recommended in SBP because it reduces renal impairment and mortality, particularly in patients at higher risk of circulatory dysfunction and hepatorenal complications. However, the prognostic impact of early albumin administration on clinical outcomes in hospitalized SBP patients remains incompletely characterized in real-world practice. This study aimed to assess the association between early albumin administration and clinical outcomes in patients hospitalized with SBP compared to those without early albumin. Methods: A retrospective cohort study was conducted using the TriNetX US Collaborative Research Network, including adults hospitalized with SBP through February 2026. Patients were divided into those receiving early albumin administration (n = 1248) and those without early albumin (n = 4932) within 24 h of index SBP diagnosis. Propensity score matching (1:1) balanced cohorts (n = 1230 each) for demographics, comorbidities, liver disease severity surrogates, medications, and laboratory values. Relative risks (RR), risk differences (RD), and hazard ratios (HR) were calculated using propensity-matched and Cox proportional hazard models. Results: Early albumin administration was associated with significantly lower all-cause mortality (RR 0.620; 95% CI: 0.441–0.871; p = 0.005 at 5 days; RR 0.770; 95% CI: 0.651–0.910; p = 0.002 at 90 days). Secondary outcomes showed reduced risks for acute kidney injury (RR 0.654; 95% CI: 0.553–0.774; p < 0.001 at 5 days; RR 0.798; 95% CI: 0.706–0.903; p < 0.001 at 90 days), hepatorenal syndrome–AKI (RR 0.598; 95% CI: 0.445–0.804; p < 0.001 at 5 days; RR 0.756; 95% CI: 0.613–0.932; p = 0.009 at 90 days), vasopressor requirement (RR 0.633; 95% CI: 0.489–0.820; p < 0.001 at 5 days; RR 0.712; 95% CI: 0.572–0.887; p = 0.002 at 30 days), and renal replacement therapy (RR 0.533; 95% CI: 0.324–0.878; p = 0.011 at 5 days; RR 0.642; 95% CI: 0.442–0.932; p = 0.019 at 30 days). Cox models confirmed statistically significant risk reductions for all primary and secondary outcomes, including ICU admission (HR 0.82; 95% CI: 0.73–0.92; p = 0.001) and 30-day readmission (HR 0.84; 95% CI: 0.73–0.97; p = 0.015). Associations were strongest in the early period and attenuated over time. Conclusions: Early albumin administration was associated with reduced risks of mortality, AKI, HRS-AKI, and hemodynamic instability in patients hospitalized with SBP, with attenuation over time. These findings support timely implementation of guideline-concordant albumin therapy, although residual confounding cannot be excluded. Full article
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17 pages, 5227 KB  
Article
Highly Selective Interfacial Route to Eight-Functional Sucrose Methacrylate for Biocompatible Scaffold Fabrication
by Vladislav Kaplin, Nikolay Glagolev, Nikita Minaev, Evgenii Epifanov, Nadezhda Aksenova, Anastasiia Akovantseva, Tatyana Zarkhina, Olga Vasileva, Elena Kiseleva, Marina Zimens, Anastasia Kuryanova, Gulnaz Mukhametova and Anna Solovieva
Polymers 2026, 18(12), 1417; https://doi.org/10.3390/polym18121417 (registering DOI) - 6 Jun 2026
Abstract
The synthesis of reactive sucrose derivatives is of significant interest for the development of novel biocompatible polymers. In this study, an octa-substituted sucrose derivative containing isocyanate groups was synthesized via a urethane-forming reaction carried out in an aprotic solvent at the phase interface. [...] Read more.
The synthesis of reactive sucrose derivatives is of significant interest for the development of novel biocompatible polymers. In this study, an octa-substituted sucrose derivative containing isocyanate groups was synthesized via a urethane-forming reaction carried out in an aprotic solvent at the phase interface. This approach exhibits high selectivity and provides a target product yield of up to 60%. Subsequently, using the same reaction mechanism, the isocyanate derivative was converted into an octa-functional methacrylate derivative capable of forming three-dimensional cross-linked networks. The structures of both the intermediate and final products were confirmed by IR, 1H NMR, and mass spectrometry. The sucrose-based prepolymer was further evaluated in the formation of cross-linked structures for potential application as bone-substituting implants. Using various photocuring techniques, including two-photon 3D printing, both plates and microstructured scaffolds were fabricated. These structures exhibited high thermal stability, elastic properties comparable to those of bone tissue, and no toxic effects on cells. Full article
(This article belongs to the Special Issue Advances in Polyurethane Synthesis and Applications)
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12 pages, 4083 KB  
Case Report
A Rare Coexistence of Biliary Atresia and Alagille Syndrome in a Neonate: Clinical Implications of Dual Etiology in Neonatal Cholestasis
by Wan-Ning Wu, Hung-Chang Lee, Hsiang-Yu Lin, Nien-Lu Wang, Wai-Tao Chan, Shu-Chao Weng and Chuen-Bin Jiang
Diagnostics 2026, 16(12), 1752; https://doi.org/10.3390/diagnostics16121752 (registering DOI) - 6 Jun 2026
Abstract
Background and Clinical Significance: Biliary atresia (BA) and Alagille syndrome (ALGS) represent distinct anatomic and genetic causes of neonatal cholestasis. Their overlapping clinical, biochemical, and early histological features present a formidable diagnostic challenge in early infancy, and their simultaneous coexistence is exceedingly [...] Read more.
Background and Clinical Significance: Biliary atresia (BA) and Alagille syndrome (ALGS) represent distinct anatomic and genetic causes of neonatal cholestasis. Their overlapping clinical, biochemical, and early histological features present a formidable diagnostic challenge in early infancy, and their simultaneous coexistence is exceedingly rare. This report documents a unique case of dual diagnosis to highlight the associated diagnostic pitfalls and implications for surgical management. Case Presentation: We present the case of a Taiwanese male neonate who manifested prolonged jaundice and acholic stools. Preoperative imaging and intraoperative cholangiography confirmed biliary atresia, for which the patient underwent a Kasai portoenterostomy. The patient subsequently exhibited an atypical postoperative course characterized by persistent hyperbilirubinemia and intractable pruritus. This atypical trajectory prompted an extensive, multisystem evaluation and molecular genetic analysis, revealing a concurrent genetic diagnosis of Alagille syndrome. To our knowledge, this dual diagnosis is rarely reported in the literature, which creates a significant challenge in determining surgical candidacy and predicting long-term liver health outcomes. Discussions: Early differentiation is complicated by the fact that some ALGS patients can initially mimic BA. Beyond its exceptional rarity, this case holds profound clinical significance for the evaluation of neonatal cholestasis, serving as a stark reminder of the risks of “diagnostic premature closure.” In diagnostically challenging cases of neonatal cholestasis, intraoperative biliary exploration remains the gold standard for the timely diagnosis of BA. Genetic testing should be considered an adjunctive tool when clinical and histological findings are inconclusive. Conclusions: This case highlights a critical clinical caveat in neonatal cholestasis: while a confirmed diagnosis of anatomical BA typically stands alone as a solitary pathology, clinicians should remain mindful of the remote possibility of a concurrent genetic etiology like ALGS in highly atypical presentations. Persistently unexpected postoperative jaundice or the accumulation of multisystem anomalies should prompt an expansion of the differential diagnosis. Recognizing this rare coexistence is crucial for effective multidisciplinary management, informed surgical decision-making, and accurate genetic counseling. Full article
(This article belongs to the Special Issue New Insights into the Diagnosis of Pediatric Cholestasis)
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15 pages, 2214 KB  
Article
Two-Dimensional CT Tumor Measurement Predicts Pathological Response and Prognosis After Neoadjuvant DCF Therapy in Esophageal Squamous Cell Carcinoma
by Takahisa Yamaguchi, Koichi Okamoto, Tetsuya Asakawa, Toshikatsu Tsuji, Jun Kinoshita, Shinichi Kadoya and Noriyuki Inaki
Cancers 2026, 18(12), 1860; https://doi.org/10.3390/cancers18121860 (registering DOI) - 6 Jun 2026
Abstract
Background/Objective: Evaluating the response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC) is challenging because primary tumors are often classified as non-measurable under the RECIST criteria. This study investigated whether two-dimensional computed tomography (CT) measurements predict pathological response and prognosis after neoadjuvant [...] Read more.
Background/Objective: Evaluating the response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC) is challenging because primary tumors are often classified as non-measurable under the RECIST criteria. This study investigated whether two-dimensional computed tomography (CT) measurements predict pathological response and prognosis after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy in ESCC. Methods: We retrospectively analyzed 123 patients who underwent radical esophagectomy following DCF therapy at two institutions (April 2011–March 2024). Changes in the short-axis, long-axis, and short-axis × long-axis diameters of the primary tumor after preoperative chemotherapy were measured on contrast-enhanced CT, and the reduction rate for each parameter was assessed. Based on the optimal cutoff values, univariate and multivariate analyses were conducted to identify significant predictors of pathological response. Results: The short-axis × long-axis diameter reduction rate (SLRR) demonstrated the highest area under the curve (0.901), with a cutoff value of 0.55 for predicting pathological response, and it was the only independent predictor in the multivariate analysis (odds ratio, 6.27; p = 0.048). In group comparisons using the SLRR cutoff value, patients with a high SLRR had significantly better 3-year recurrence-free survival (67.8% vs. 29.4%, p < 0.001) and overall survival (79.5% vs. 46.6%, p < 0.001) than those with a low SLRR. Conclusions: The CT-based SLRR independently predicts both pathological response and prognosis after neoadjuvant DCF therapy in ESCC. Full article
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13 pages, 749 KB  
Article
Chorioamnionitis and Neonatal Morbidity and Mortality in Extremely Preterm Infants Born at 23–28 Weeks: A Single-Centre Retrospective Study
by Gabriela C. Zaharie, Monica G. Hăşmăşanu, Ernestine Haralambous, Flaviu A. Zaharie, Anna D. Jakab and Melinda Matyas
J. Clin. Med. 2026, 15(12), 4406; https://doi.org/10.3390/jcm15124406 (registering DOI) - 6 Jun 2026
Abstract
Background/Objectives: Chorioamnionitis (CA), an inflammation, with or without infection, involving the amniotic fluid, placenta, fetal membranes or decidua, can significantly impact fetal and neonatal development. This study aimed to determine the prevalence of chorioamnionitis and confirm its correlation with neonatal morbidity and mortality, [...] Read more.
Background/Objectives: Chorioamnionitis (CA), an inflammation, with or without infection, involving the amniotic fluid, placenta, fetal membranes or decidua, can significantly impact fetal and neonatal development. This study aimed to determine the prevalence of chorioamnionitis and confirm its correlation with neonatal morbidity and mortality, in a single tertiary center. Methods: This observational, retrospective study was conducted over three years (2019–2021) in a tertiary neonatal intensive care unit, examining 80 preterm infants born at 23–28 weeks of gestation. Spearman rank correlation, χ2 tests, and multivariate logistic regression were used to assess associations between chorioamnionitis exposure and neonatal outcomes. Results: Among the 80 newborns analysed, clinical chorioamnionitis was identified in 12 preterm infants, while 65 (81.3%) presented histological chorioamnionitis. No significant association was found between histological chorioamnionitis stage and gestational age at birth (Spearman ρ = −0.15, p = 0.195). Premature rupture of membranes was significantly more frequent in the CA-exposed group (46.2% vs. 13.3%, p = 0.019). In unadjusted analyses, histological chorioamnionitis exposure was associated with higher rates of adverse neonatal outcomes, including early-onset sepsis (46.2% vs. 26.7%), intraventricular haemorrhage (73.8% vs. 60.0%), bronchopulmonary dysplasia (15.9% vs. 6.7%), and retinopathy of prematurity (11.3% vs. 0.0%); however, most of these differences did not reach statistical significance. After multivariate adjustment, histological chorioamnionitis remained independently associated with severe respiratory distress syndrome (adjusted OR 25.84, 95% CI 2.49–268.44, p = 0.006). Mortality was numerically lower in the CA-exposed group (27.7% vs. 46.7%); however, this difference did not reach statistical significance (p = 0.216). Conclusions: Histological chorioamnionitis was independently associated with severe respiratory distress syndrome. Associations with early onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity were observed in unadjusted analyses but were not independently significant after adjustment for perinatal confounders. No significant association was found between chorioamnionitis and neonatal mortality. While clinical diagnostic criteria for chorioamnionitis demonstrated good specificity, their poor sensitivity underscores the urgent need for improved diagnostic tools, including routine histological examination of the placenta. Full article
(This article belongs to the Section Clinical Pediatrics)
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23 pages, 1171 KB  
Review
Can Buprenorphine Be Overdosed? The Ceiling Effect and Its Clinical Implications
by Rozalia Beata Kozińska, Julia Ślęzak, Ignacy Ilski, Maja Podsiadła, Kamil Biedka and Emilia Królewicz
Pharmaceuticals 2026, 19(6), 903; https://doi.org/10.3390/ph19060903 (registering DOI) - 6 Jun 2026
Abstract
Opioids comprise a class of substances characterized by a narrow therapeutic window and significant euphoric effects. Opioid-related mortality remains a critical global health issue, primarily resulting from respiratory depression associated with full μ-opioid receptor agonists. Buprenorphine is distinguished by its pharmacological profile as [...] Read more.
Opioids comprise a class of substances characterized by a narrow therapeutic window and significant euphoric effects. Opioid-related mortality remains a critical global health issue, primarily resulting from respiratory depression associated with full μ-opioid receptor agonists. Buprenorphine is distinguished by its pharmacological profile as a partial μ-opioid receptor agonist, exhibiting a ceiling effect on both respiratory depression and euphoria. These characteristics render buprenorphine particularly valuable in opioid replacement therapy for opioid use disorder and in the management of both chronic and acute pain. Current literature indicates that, due to these properties, buprenorphine possesses a superior safety profile compared to other opioids. This narrative review evaluates whether buprenorphine can cause fatal overdose despite its protective ceiling effect and examines cases of buprenorphine-related fatalities. The review synthesizes data from pre-clinical, clinical, pharmacological, and toxicological studies. Current literature supports the consensus that the established ceiling effect on respiratory depression does not fully eliminate the risk of fatal overdose. Polysubstance use, particularly co-ingestion of other central nervous system depressants, significantly increases this risk, and most buprenorphine-related deaths involve such combinations. Additionally, buprenorphine’s safety is reduced in vulnerable populations, including opioid-naive individuals, children, and patients with pre-existing respiratory compromise. While buprenorphine alone presents a substantially lower fatality risk compared to other opioids, the ceiling effect is pharmacodynamic rather than absolute, and toxicity or fatal overdose may still occur. Current data gathered from clinical and pre-clinical studies suggest that buprenorphine is safer than full μ-opioid receptor agonists, but it is not without risk. The ceiling effect’s protective benefits depend on context. Therefore, despite its improved safety profile, buprenorphine should not be regarded as risk-free. Full article
(This article belongs to the Special Issue Pharmacology and Toxicology of Opioids, 2nd Edition)
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19 pages, 1864 KB  
Review
Aggregation-Induced Emission (AIE) Probe-Labeled Nanotheranostics: A Mini-Review
by Yilin Ma, Yingying Li, Chuanbin Wu, Yao Yang, Xin Pan and Zhengwei Huang
Pharmaceuticals 2026, 19(6), 902; https://doi.org/10.3390/ph19060902 (registering DOI) - 6 Jun 2026
Abstract
Nanotheranostics integrate theranostic functions onto a single nanoscale platform, and have become a new approach in precision medicine. Nanotheranostics rely on probes. However, traditional fluorescent probes often exhibit aggregation-caused quenching (ACQ) when loaded at high concentrations onto nanocarriers, severely limiting their imaging performance. [...] Read more.
Nanotheranostics integrate theranostic functions onto a single nanoscale platform, and have become a new approach in precision medicine. Nanotheranostics rely on probes. However, traditional fluorescent probes often exhibit aggregation-caused quenching (ACQ) when loaded at high concentrations onto nanocarriers, severely limiting their imaging performance. Aggregation-induced emission agents (AIEgens) offer a solution to this long-standing problem through their ability to enhance fluorescence during aggregation. This mini-review systematically outlines nanotheranostic systems based on aggregation-induced emission (AIE). We first introduce the basic mechanism of AIE (the limitation of molecular internal motion) and its advantages over traditional fluorescent probes. Then, we discuss the design strategies of AIE nanoprobes according to the types of nanocarriers (including liposomes, polymer nanoparticles, and self-assembling systems). Additionally, we emphasize the disease-specific AIE nanotheranostic designs tailored for pathological microenvironments such as tumors, neurodegenerative diseases, and inflammatory diseases. Finally, we conduct an in-depth analysis of the current challenges hindering clinical translation, and propose future AIE nanotheranostic technologies applicable to clinical practice and the direction for personalized medicine. Full article
(This article belongs to the Section Pharmaceutical Technology)
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12 pages, 227 KB  
Article
Exploratory Analysis of Associations Between Body Weight Status, Lipid Profile, and Lifestyle Factors in School-Aged Children in a Developing Country
by Nela S. Papovic, Nikola Prodanovic, Djordje Kolak, Biljana Vuletic, Katerina Dajic, Suzana Zivojinovic and Tijana Prodanovic
Obesities 2026, 6(3), 39; https://doi.org/10.3390/obesities6030039 (registering DOI) - 6 Jun 2026
Abstract
Objective: To investigate the associations between body weight status and anthropometric parameters, lipid profile, eating behavior characteristics, and physical activity levels among children in a developing country. Methods: The study included 80 children aged 7–11 years, divided into two groups: children with normal [...] Read more.
Objective: To investigate the associations between body weight status and anthropometric parameters, lipid profile, eating behavior characteristics, and physical activity levels among children in a developing country. Methods: The study included 80 children aged 7–11 years, divided into two groups: children with normal body weight (n = 40) and children with overweight or obesity classified using WHO BMI-for-age growth reference standards (overweight >+1 SD, obesity >+2 SD). BMI, waist circumference, and lipid profile (total cholesterol, LDL, HDL, triglycerides) were measured. Eating behavior characteristics and physical activity levels were assessed using standardized questionnaires. Statistical analysis included descriptive statistics, comparative tests, correlation analysis, and exploratory regression models. Results: Children with increased body weight had significantly higher BMI, waist circumference, and a more unfavorable lipid profile (p < 0.01). BMI showed a positive correlation with food enjoyment, emotional overeating, and eating speed, and a negative correlation with satiety responsiveness and food fussiness. Lower physical activity levels were associated with higher BMI and higher total cholesterol in unadjusted analyses. Conclusions: Excess body weight among children in a developing country is associated with metabolic and behavioral characteristics in this sample. Given the cross-sectional design and limited sample size, findings should be interpreted as exploratory. The findings highlight associations between body weight status, metabolic parameters, eating behavior, and physical activity, without implying causality due to the cross-sectional design. Full article
16 pages, 1432 KB  
Article
Using Explainable Machine Learning to Identify Determinants of Spinal Deformities in Children: It’s Not Only About What, but Also About How
by Dragica Bukumirić, Aleksandra Ilić, Mirjana Pajčin, Aleksandar Ćorac, Saša Milićević, Verica Jovanović, Živko Bojović, Ilija Doknić, Sindi Mitrović, Zoran Bukumirić, Zorica Terzić-Šupić, Jovana Todorović and Srđan Mašić
Healthcare 2026, 14(12), 1601; https://doi.org/10.3390/healthcare14121601 (registering DOI) - 6 Jun 2026
Abstract
Background: Spinal deformities in children represent a relevant public health issue, with possible long-term consequences. Timely identification of their determinants is essential for adequate prevention. Methods: This study was a secondary analysis of data from the 2019 Serbian National Health Survey, including 1309 [...] Read more.
Background: Spinal deformities in children represent a relevant public health issue, with possible long-term consequences. Timely identification of their determinants is essential for adequate prevention. Methods: This study was a secondary analysis of data from the 2019 Serbian National Health Survey, including 1309 children aged 5–14 years. Logistic regression with LASSO regularization and multiple ML algorithms were tested, with XGBoost selected as the optimal model. Class imbalance was addressed using class weighting and SMOTE. Model interpretability was achieved using SHAP analysis. Results: The prevalence of spinal deformities was 8.6%. Univariable analyses showed that age, poorer self-rated health, chronic illness, recent injuries, and pes planus were significantly associated with spinal deformities. Family-related variables showed no significant associations. Among the evaluated models, XGBoost demonstrated the most stable performance across the applied evaluation metrics and the best balance between predictive performance and interpretability. SHapley Additive exPlanations (SHAP) analysis showed that pes planus was the strongest determinant, followed by age and chronic illness, while socio-demographic and family factors had minimal influence. Conclusion: Explainable machine learning models, particularly XGBoost combined with SHAP, can allow for the identification and interpretation of key determinants of spinal deformities in children. Pes planus was shown to be modifiable and relevant associated determinant, supporting its importance in early screening and preventive strategies. Full article
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30 pages, 935 KB  
Review
Dietary Polysaccharides in Skin Health: Structure–Function Relationships and Implications for Nutritional Dermatology
by Li Zhao, Zhenzhi Chen, Yujie Sun, Ke Jia, Yunjia Liu and Ping Li
Nutrients 2026, 18(12), 1838; https://doi.org/10.3390/nu18121838 (registering DOI) - 6 Jun 2026
Abstract
Skin health depends on the coordinated maintenance of barrier integrity, immune homeostasis, redox balance, microbial ecology, and systemic metabolic status. Among dietary constituents, polysaccharides have attracted increasing attention because they represent a structurally heterogeneous class of complex carbohydrates whose biological behavior is shaped [...] Read more.
Skin health depends on the coordinated maintenance of barrier integrity, immune homeostasis, redox balance, microbial ecology, and systemic metabolic status. Among dietary constituents, polysaccharides have attracted increasing attention because they represent a structurally heterogeneous class of complex carbohydrates whose biological behavior is shaped by molecular weight, monosaccharide composition, glycosidic linkage patterns, branching, higher-order conformation, and physicochemical properties. However, many current skin-related studies remain primarily phenomenon-driven, with insufficient attention to how specific structural features influence biological function and dermatologic relevance. From a structure–function perspective, key structural features of dietary polysaccharides may influence several skin-relevant biological processes, including microbiota-associated signaling, immune regulation, barrier homeostasis, oxidative balance, and extracellular matrix protection. The relevance of these structure-linked functions differs across dermatologic contexts: it appears most direct in photoaging, more conditional in atopic dermatitis, and relatively indirect in psoriasis, whereas wound-repair-related settings are less closely aligned with strict dietary relevance. Current evidence therefore supports structure–function associations more strongly than direct associations between specific structural features and dermatologic outcomes. Dietary polysaccharides are not functionally interchangeable in skin-related contexts, and their skin-related effects depend on structural background, disease setting, and mode of application. Where non-dietary evidence is discussed, it serves primarily as mechanistic or translational contextualization rather than as a basis for nutritional recommendation. Clarifying these relationships may support future mechanistic research and facilitate more rational nutritional applications of dietary polysaccharides in skin health. Full article
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