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12 pages, 893 KB  
Proceeding Paper
Real-Time Pollutant Forecasting Using Edge–AI Fusion in Wastewater Treatment Facilities
by Siva Shankar Ramasamy, Vijayalakshmi Subramanian, Leelambika Varadarajan and Alwin Joseph
Eng. Proc. 2025, 117(1), 31; https://doi.org/10.3390/engproc2025117031 - 22 Jan 2026
Abstract
Wastewater treatment is one of the major challenges in the reuse of water as a natural resource. Cleaning of water depends on analyzing and treating the water for the pollutants that have a significant impact on the quality of the water. Detecting and [...] Read more.
Wastewater treatment is one of the major challenges in the reuse of water as a natural resource. Cleaning of water depends on analyzing and treating the water for the pollutants that have a significant impact on the quality of the water. Detecting and analyzing the surges of these pollutants well before the recycling process is needed to make intelligent decisions for water cleaning. The dynamic changes in pollutants need constant monitoring and effective planning with appropriate treatment strategies. We propose an edge-computing-based smart framework that captures data from sensors, including ultraviolet, electrochemical, and microfluidic, along with other significant sensor streams. The edge devices send the data from the cluster of sensors to a centralized server that segments anomalies, analyzes the data and suggests the treatment plan that is required, which includes aeration, dosing adjustments, and other treatment plans. A logic layer is designed at the server level to process the real-time data from the sensor clusters and identify the discharge of nutrients, metals, and emerging contaminants in the water that affect the quality. The platform can make decisions on water treatments using its monitoring, prediction, diagnosis, and mitigation measures in a feedback loop. A rule-based Large Language Model (LLM) agent is attached to the server to evaluate data and trigger required actions. A streamlined data pipeline is used to harmonize sensor intervals, flag calibration drift, and store curated features in a local time-series database to run ad hoc analyses even during critical conditions. A user dashboard has also been designed as part of the system to show the recommendations and actions taken. The proposed system acts as an AI-enabled system that makes smart decisions on water treatment, providing an effective cleaning process to improve sustainability. Full article
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28 pages, 2866 KB  
Article
Red and White Grape Pomace Possess Cardioprotective Effects by Modulating Inflammation and Oxidative Stress in Experimental Ischemic Heart Disease
by Dan Claudiu Măgureanu, Raluca Maria Pop, Veronica Sanda Chedea, Paul-Mihai Boarescu, Mădălina Luciana Gherman, Ștefan Horia Roșian, Floricuța Ranga, Ioana Sorina Giurca, Elena Mihaela Jianu, Adriana Florinela Cătoi, Anca Dana Buzoianu and Ioana Corina Bocsan
Molecules 2026, 31(2), 383; https://doi.org/10.3390/molecules31020383 - 21 Jan 2026
Viewed by 47
Abstract
Background: Cardiac ischemia (CI) remains a leading cause of death worldwide, prompting an ongoing search for new treatment options. This study explored and compared the preventive cardioprotective effects of polyphenols extracted from red (RGP) and white grape pomace (WGP) against isoproterenol (ISO)-induced myocardial [...] Read more.
Background: Cardiac ischemia (CI) remains a leading cause of death worldwide, prompting an ongoing search for new treatment options. This study explored and compared the preventive cardioprotective effects of polyphenols extracted from red (RGP) and white grape pomace (WGP) against isoproterenol (ISO)-induced myocardial ischemia, with a focus on their antioxidant and anti-inflammatory properties. Materials and Methods: Fifty male Wistar rats were divided into five groups: I—Saline, II—Saline+ISO, III—Ramipril+ISO, IV—WGP+ISO, and V—RGP+ISO. CI was induced in Groups II–V with ISO (45 mg/kg, on day 13), a dose widely used to reproducibly induce myocardial ischemic injury in experimental models. Electrocardiographic parameters, serum oxidative markers, cytokines, and tissue homogenates from the liver and heart were analyzed on day 14. Results: ISO significantly shortened the RR interval and increased the ventricular rate, without significant modulation by any treatment. The reduction in R-wave amplitude caused by ISO was lessened in all treated groups, with RGP showing values closer to Saline (RGP+ISO vs. Saline, p = 0.329). No differences were found among groups for PR segment, QRS duration, QT, or QTc intervals. Furthermore, all treated groups (III–V) showed significant improvements in oxidative and inflammatory markers compared to Saline+ISO (p < 0.05), with RGP demonstrating the strongest antioxidant activity by maintaining MDA and NO levels close to Saline (RGP+ISO vs. Saline, p > 0.05), while WGP exhibited superior anti-inflammatory effects in cardiac tissue by preserving IL-6 and IL-1β levels comparable to controls (WGP+ISO vs. Saline, p > 0.05). Conclusions: Grape pomace, especially RGP, may offer cardioprotection by decreasing oxidative stress, while WGP more effectively reduces inflammation. The complementary antioxidant and anti-inflammatory effects observed suggest that combining GP extracts may represent a promising hypothesis for future cardiovascular research. Full article
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39 pages, 4728 KB  
Review
Advancing Sustainable Agriculture Through Aeroponics: A Critical Review of Integrated Water–Energy–Nutrient Management and Environmental Impact Mitigation
by Shen-Wei Chu and Terng-Jou Wan
Agriculture 2026, 16(2), 265; https://doi.org/10.3390/agriculture16020265 - 21 Jan 2026
Viewed by 59
Abstract
Aeroponics has emerged as a key technology for sustainable and resource-efficient food production, particularly under intensifying constraints on water availability, land use, and greenhouse gas (GHG) emissions. This review synthesizes recent advances in water–energy–nutrient integration, highlighting operational parameters—humidity (50–80%), temperature (18–25 °C), nutrient [...] Read more.
Aeroponics has emerged as a key technology for sustainable and resource-efficient food production, particularly under intensifying constraints on water availability, land use, and greenhouse gas (GHG) emissions. This review synthesizes recent advances in water–energy–nutrient integration, highlighting operational parameters—humidity (50–80%), temperature (18–25 °C), nutrient solution pH (5.5–6.5), and electrical conductivity (1.5–2.5 mS cm−1)—that critically influence system performance. Evidence indicates that closed-loop water recirculation and AI-assisted monitoring for environmental control and nutrient dosing can stabilize system dynamics and reduce water consumption by more than 90%. Reported yield improvements ranged from 45% to 75% compared with conventional soil-based cultivation. Moreover, systems powered by renewable energy demonstrated up to an 80% reduction in GHG emissions. Life-cycle assessment studies further suggest that aeroponics, coupled with low-carbon electricity in controlled-environment agriculture (CEA), can outperform traditional agricultural supply chains in climate and resource efficiency metrics. Additional technological innovations—including multi-tier vertical rack architectures, optimized misting intervals, and micronutrient-enriched fertigation formulations containing N, P, Ca, Mg, and K—were found to enhance spatial productivity and crop quality. Overall, aeroponics represents a promising pathway toward net-zero, high-performance agricultural systems. Full article
(This article belongs to the Section Agricultural Systems and Management)
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16 pages, 632 KB  
Article
Impact of Predischarge NT-proBNP on Treatment Optimisation in Acute Heart Failure
by Marija Polovina, Milenko Tomić, Milica Janković, Danka Civrić, Andrea Stojićević, Stefan Stanković, Teodora Pejović, Mihajlo Viduljević, Gordana Krljanac, Milika Ašanin, Sanja Stanković and Petar M. Seferović
Int. J. Mol. Sci. 2026, 27(2), 1028; https://doi.org/10.3390/ijms27021028 - 20 Jan 2026
Viewed by 94
Abstract
Residual congestion (RC) at discharge predicts adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Its impact on the implementation of guideline-directed medical therapies (GDMT) remains unclear. N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory during hospitalisation reflects RC and may be associated with [...] Read more.
Residual congestion (RC) at discharge predicts adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Its impact on the implementation of guideline-directed medical therapies (GDMT) remains unclear. N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory during hospitalisation reflects RC and may be associated with GDMT implementation. The aim was to assess whether discharge NT-proBNP and a fall in NT-proBNP < 30% during hospitalisation (ΔNT-proBNP < 30%) predict GDMT underuse in acute HFrEF. In this prospective observational study, NT-proBNP was measured at hospital admission and 48–72 h before discharge. Provision of individual GDMT drug classes was assessed and GDMT underuse was defined as prescription of <3 key GDMT drug classes at discharge. 391 HFrEF patients (mean age, 69.9 ± 13.1years, 67.3% male) were included. ΔNT-proBNP < 30% was identified in 108 (27.6%). Higher discharge NT-proBNP was independently associated with lower likelihood of prescribing ACE-inhibitors, sacubitril/valsartan, eplerenone/spironolactone, or empagliflozin/dapagliflozin. ΔNT-proBNP < 30% was associated with 17% higher odds of GDMT underuse (95% confidence interval, 1.10–1.31, p < 0.001), regardless of clinical characteristics or in-hospital management. Patients with ΔNT-proBNP < 30% were discharged on lower doses of titratable GDMT medications. In-hospital NT-proBNP burden and trajectory, as markers of RC, are associated with GDMT underutilisation at discharge in acute HFrEF. Addressing RC may impact treatment quality in acute HFrEF. Full article
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9 pages, 1389 KB  
Case Report
Progressive Destructive Hypothyroidism Associated with Sunitinib Therapy: A Three-Year Case Analysis
by Marcin Nosal
J. Clin. Med. 2026, 15(2), 788; https://doi.org/10.3390/jcm15020788 - 19 Jan 2026
Viewed by 70
Abstract
Sunitinib, a tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs), is widely used in renal cell carcinoma. A broad spectrum of thyroid dysfunctions has been observed during TKI therapy, yet their mechanisms and clinical [...] Read more.
Sunitinib, a tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs), is widely used in renal cell carcinoma. A broad spectrum of thyroid dysfunctions has been observed during TKI therapy, yet their mechanisms and clinical progression remain only partially explained. A longitudinal case analysis of a woman with metastatic clear-cell renal cell carcinoma treated with cyclical sunitinib therapy (4 weeks on, 2 weeks off) was performed. Thyroid function tests, clinical symptoms, and ultrasound imaging findings were evaluated over time and compared with treatment exposure and dose adjustments. Baseline thyroid function was normal. During the third cycle, thyroid-stimulating hormone (TSH) increased markedly (33.44–41.26 mIU/L), with free thyroid hormones initially remaining within reference limits. TSH fluctuations corresponded to treatment intervals before stabilising into persistent hypothyroidism requiring levothyroxine replacement. Thyroid ultrasound revealed progressive parenchymal destruction and a reduction in gland volume from 18 mL to approximately 2 mL over three years. Endocrine management enabled maintenance of biochemical euthyroidism, and systemic oncological treatment continued without interruption. Sunitinib treatment may lead to progressive destructive hypothyroidism. Routine surveillance of thyroid function is essential, and timely levothyroxine therapy facilitates continued anticancer treatment and symptom control. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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14 pages, 6019 KB  
Article
Long-Term In Situ Monitoring of Ambient Gamma Dose Equivalent Rates in Macedonia: Temporal Trends from 2010 to 2020
by Lambe Barandovski, Irena Zlatanovska, Trajče Stafilov, Robert Šajn and Aneta Gacovska-Barandovska
Atmosphere 2026, 17(1), 104; https://doi.org/10.3390/atmos17010104 - 19 Jan 2026
Viewed by 117
Abstract
In situ measurements of ambient dose equivalent rates were conducted across the territory of Macedonia at five-year intervals in 2010, 2015, and 2020. Data were collected from 68 uniformly distributed locations in 2010 and from 72 locations in both 2015 and 2020, ensuring [...] Read more.
In situ measurements of ambient dose equivalent rates were conducted across the territory of Macedonia at five-year intervals in 2010, 2015, and 2020. Data were collected from 68 uniformly distributed locations in 2010 and from 72 locations in both 2015 and 2020, ensuring representative spatial coverage. The main objective of this study was to establish a baseline dataset of outdoor gamma dose rates, evaluate their potential temporal variations, and identify the dominant factors influencing their spatial variability. The results indicate a high degree of temporal stability over the investigated decade, with mean values of 113 nSv/h in 2010 and 110 nSv/h in both 2015 and 2020. Following descriptive statistical analysis, spatial distribution maps were created, revealing that the observed dose rate variability is primarily associated with the country’s diverse geology rather than anthropogenic sources. These findings confirm the reliability of direct in situ monitoring and provide a robust reference framework for assessing environmental and atmospheric contributions to external gamma radiation exposure in Macedonia. Full article
(This article belongs to the Section Atmospheric Techniques, Instruments, and Modeling)
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18 pages, 304 KB  
Article
HPV Vaccination Completion Among Men Who Have Sex with Men Using HIV Pre-Exposure Prophylaxis in Brazil: A Cross-Sectional Study
by Alvaro Francisco Lopes de Sousa, Lariane Angel Cepas, Isadora Silva de Carvalho, Caíque Jordan Nunes Ribeiro, Guilherme Reis de Santana Santos, Jean Carlos Soares da Silva, Talia Gomes Luz, Ruan Nilton Rodrigues Melo, Lucas Brandão dos Santos, Julia Bellini Sorrente, Gabriela Amanda Falsarella, Antonio Luis Ferreira Calaço and Ana Paula Morais Fernandes
Vaccines 2026, 14(1), 92; https://doi.org/10.3390/vaccines14010092 - 18 Jan 2026
Viewed by 259
Abstract
Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of [...] Read more.
Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of this study were to estimate the prevalence of complete HPV vaccination and to identify factors associated with vaccination completion among MSM using PrEP in Brazil. Methods: We conducted a cross-sectional online survey between May and September 2025 among MSM aged ≥18 years, residing in Brazil and currently using oral PrEP. Participants were recruited through virtual snowball sampling and targeted advertisements on social media and a gay geosocial networking application. Data were collected using a structured, self-administered questionnaire hosted on REDCap®. Complete HPV vaccination was defined as self-reported receipt of all doses recommended according to the participant’s age and clinical condition. Sociodemographic characteristics, relationship patterns, sexual behaviors, lubricant use during sexual activity, and history of sexually transmitted infections (STIs) were assessed. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (95% CIs) were estimated using Poisson regression with robust (sandwich) variance. Results: A total of 872 MSM using PrEP were included, of whom 59.4% reported complete HPV vaccination. In adjusted analyses, complete vaccination was more frequent among participants reporting both steady and casual partners (aPR = 1.90; 95% CI: 1.36–2.65) or only casual partners (aPR = 1.72; 95% CI: 1.24–2.39), those reporting lubricant use during sexual activity (aPR = 1.41; 95% CI: 1.23–1.61), and those with a diagnosis of chlamydia and/or gonorrhea in the previous 12 months (aPR = 1.22; 95% CI: 1.08–1.36). Conclusions: Although HPV vaccination coverage among MSM using PrEP in Brazil is higher than that reported for MSM in general, it remains incomplete in a population with regular contact with specialized health services. Integrating systematic assessment and delivery of HPV vaccination into PrEP care may help increase vaccination completion and reduce missed opportunities for prevention. Full article
16 pages, 1147 KB  
Article
Blood Transfusion Risk Following Early Versus Delayed Surgery in Hip Fracture Patients on Direct Oral Anticoagulants: A Study Protocol for a Natural Experiment
by Tim Schiepers, Diederik Smeeing, Hugo Wijnen, Hanna Willems, Frans Jasper Wijdicks, Elvira Flikweert, Diederik Kempen, Eelke Bosma, Johannes H. Hegeman, Marielle Emmelot-Vonk, Detlef van der Velde and Henk Jan Schuijt
J. Clin. Med. 2026, 15(2), 758; https://doi.org/10.3390/jcm15020758 - 16 Jan 2026
Viewed by 197
Abstract
Background: Early surgical intervention is associated with improved outcomes in hip fracture care, yet in patients using Direct Oral Anticoagulants (DOACs), surgery is frequently delayed due to concerns about increased intraoperative bleeding. Despite the increasing prevalence of hip fracture patients on DOACs, [...] Read more.
Background: Early surgical intervention is associated with improved outcomes in hip fracture care, yet in patients using Direct Oral Anticoagulants (DOACs), surgery is frequently delayed due to concerns about increased intraoperative bleeding. Despite the increasing prevalence of hip fracture patients on DOACs, no consensus exists on optimal surgical timing. This has led to substantial practice variation between hospitals, with some operating within 24 h of last DOAC intake and others delaying surgery beyond 24 h. This study hypothesizes that early surgery within 24 h results in a non-inferior blood transfusion risk compared to delayed surgery 24 h or more after last DOAC intake in hip fracture patients on DOACs. This protocol describes the design and methodological rationale of a natural experiment. Methods and analysis: A multicenter cohort study designed as a natural experiment will be conducted across seven Dutch level 2 trauma centers, using predefined and standardized prospectively collected variables from electronic health records. Centers will adhere to distinct local surgical timing protocols, forming two cohorts: early surgery within 24 h and delayed surgery 24 h or more after last DOAC intake. Patients presenting with an isolated hip fracture who are using a DOAC and have taken their last dose within 24 h before admission will be included. The primary endpoint is postoperative blood transfusion. Secondary endpoints include additional bleeding-related outcomes, thrombotic and postoperative complications, and hospital length of stay. The primary analysis will be conducted on a per-protocol basis, with an intention-to-treat analysis performed as a supplementary assessment. Non-inferiority will be established if the upper bound of the one-sided 95% confidence interval for the risk difference does not exceed the predefined margin of 5%. Ethics and dissemination: Ethical approval was obtained from the Medical Ethics Committee United, Utrecht, The Netherlands. As this is a cohort study without altering clinical care, individual informed consent is not required. All data will be pseudonymized, and findings will be disseminated through peer-reviewed journals and scientific conferences. Registration details: Medical Ethics Committee United, Utrecht, The Netherlands, registration number W25.034. Full article
(This article belongs to the Special Issue Challenges and Solutions in Geriatric Fracture)
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14 pages, 653 KB  
Article
Impact of High-Dose Cefepime During the Initial 48 h on Intensive Care Unit Survival in Sepsis: A Retrospective Observational Study
by Tsukasa Kuwana, Kosaku Kinoshita, Yuma Kanai, Yurina Yamaya, Ken Takahashi, Satoshi Ishizuka and Toru Imai
Antibiotics 2026, 15(1), 88; https://doi.org/10.3390/antibiotics15010088 - 15 Jan 2026
Viewed by 157
Abstract
Background/Objectives: Sepsis is a life-threatening condition associated with high mortality. Optimal dosing strategies for β-lactam antibiotics in sepsis remain controversial, particularly in patients with renal impairment. Cefepime (CFPM) is widely used as empiric therapy; however, its appropriate initial dosing in critically ill patients [...] Read more.
Background/Objectives: Sepsis is a life-threatening condition associated with high mortality. Optimal dosing strategies for β-lactam antibiotics in sepsis remain controversial, particularly in patients with renal impairment. Cefepime (CFPM) is widely used as empiric therapy; however, its appropriate initial dosing in critically ill patients is unclear. This study aimed to evaluate whether high-dose CFPM administration during the first 48 h improves survival in patients with sepsis, irrespective of renal function. Methods: This single-center, retrospective, observational study included adult intensive care unit (ICU) patients with sepsis who received CFPM as initial therapy between January 2017 and December 2024. Patients were categorized into High-dose (12 g within 48 h; 2 g every 8 h) and Low-dose (<12 g/48 h) groups. The primary outcome was ICU survival. To address confounding, inverse probability of treatment weighting (IPTW) based on serum creatinine was applied, with sensitivity analyses using 1% trimmed and stabilized IPTW. Results: Of 122 eligible patients, 84 were analyzed (High-dose: n = 27; Low-dose: n = 57). After IPTW adjustment, high-dose CFPM was significantly associated with improved ICU survival (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.60–18.39, p = 0.0066). This association remained consistent in the 1% trimmed IPTW analysis (OR 4.07, 95% CI 1.19–13.97, p = 0.0256). Stabilized IPTW yielded a similar effect estimate, though without statistical significance (OR 5.43, 95% CI 0.72–41.16, p = 0.1017). Overall, results were consistent in direction and magnitude across models. Conclusions: High-dose CFPM administration during the initial 48 h was associated with improved ICU survival in patients with sepsis, independent of renal function. Full article
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17 pages, 2213 KB  
Review
The Differential Effects of Vitamin K Across Glycaemic Outcomes in Prediabetes and Type 2 Diabetes Mellitus
by Syeda Ruwaida Ahmed, Kabelo Mokgalaboni and Wendy N. Phoswa
Nutrients 2026, 18(2), 269; https://doi.org/10.3390/nu18020269 - 14 Jan 2026
Viewed by 275
Abstract
Background: Vitamin K has emerged as a promising regulator of glucose metabolism in preclinical studies. There is, however, scant evidence to support this promising potential in a clinical setting. Aim: The aim of this study was to confirm the effects of vitamin K [...] Read more.
Background: Vitamin K has emerged as a promising regulator of glucose metabolism in preclinical studies. There is, however, scant evidence to support this promising potential in a clinical setting. Aim: The aim of this study was to confirm the effects of vitamin K supplementation on glycaemic parameters such as fasting blood glucose (FBG), fasting insulin (FI), glycated haemoglobin (HbA1c), insulin resistance (HOMA-IR), and homeostatic model of beta cell function (HOMA-β) across randomised controlled trials (RCTs). Materials and Methods: This meta-analysis used evidence from PubMed, Scopus, and manual screening. Only RCTs were considered for this meta-analysis of interventional studies. The Meta online tool was used to analyse data, with the results reported as either the mean or the standardised mean difference (SMD), alongside 95% confidence intervals (CI). Results: Only eight RCTs were found relevant and analysed; the age of those in the vitamin K group was 50.58 ± 6.91 years, and in the control group, it was 48.19 ± 5.41. The evidence showed a significant reduction in FBG, SMD = −0.22 (−0.39 to −0.05), HbA1c, MD = −1.00%, 95% CI (−1.92 to −0.07), and HOMA-IR, MD = −0.63, 95% CI (−1.20 to −0.06). However, no effect was observed on insulin (SMD = −0.39, 95% CI: −0.91 to 0.13, p = 0.15) and HOMA-β (MD = 6.56, 95% CI (−3.89 to 17.01), p = 0.2184. Low doses of vitamin K2 and vitamin K1 were associated with reduced HbA1c and HOMA-IR, respectively. An intervention of less than 12 weeks was associated with reduced HOMA-IR. Conclusions: This study showed a significant decrease in FBG, HbA1c, and HOMA-IR without affecting insulin or HOMA-β. Nevertheless, the limited number of trials with moderate quality warrants larger, longer-term RCTs with rigorous methodology and direct comparisons of vitamin K isoforms to better assess therapeutic potential. Full article
(This article belongs to the Special Issue Vitamins and Human Health: 3rd Edition)
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13 pages, 1990 KB  
Article
Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone
by Yuki Otsuka, Yoshiaki Soejima, Yasuhiro Nakano, Atsuhito Suyama, Ryosuke Takase, Kohei Oguni, Yohei Masuda, Daisuke Omura, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Hiroyuki Honda, Kazuki Tokumasu, Keigo Ueda and Fumio Otsuka
Int. J. Mol. Sci. 2026, 27(2), 832; https://doi.org/10.3390/ijms27020832 - 14 Jan 2026
Viewed by 274
Abstract
Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. [...] Read more.
Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. Full article
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15 pages, 258 KB  
Article
Effect of a Constant Rate Infusion of Ketamine on a Variable Rate Infusion of Xylazine in Standing Horses Undergoing Ventriculocordectomy and Laryngoplasty
by Francisco Medina-Bautista, Juan Morgaz, Setefilla Quirós-Carmona, María Esther Caravaca-Paredes, Rocío Navarrete-Calvo, Antonia Lucía Sánchez de Medina, Rafael Gómez-Villamandos and María del Mar Granados
Vet. Sci. 2026, 13(1), 77; https://doi.org/10.3390/vetsci13010077 - 12 Jan 2026
Viewed by 271
Abstract
Standing sedation in horses provides immobilization and analgesia for surgery while avoiding the high risks of general anesthesia. Ketamine at subanesthetic doses may enhance sedation and reduce xylazine requirements, but evidence in clinical settings is limited. In a randomized blinded trial, we evaluated [...] Read more.
Standing sedation in horses provides immobilization and analgesia for surgery while avoiding the high risks of general anesthesia. Ketamine at subanesthetic doses may enhance sedation and reduce xylazine requirements, but evidence in clinical settings is limited. In a randomized blinded trial, we evaluated whether adding a low-dose ketamine infusion could reduce the xylazine dose required for effective sedation during standing ventriculocordectomy and laryngoplasty. Fifty-one horses were randomly assigned to sedation with xylazine alone (SX group) or xylazine plus ketamine (KX group) in a continuous rate infusion. The ketamine group received ketamine (0.25 mg/kg intravenous (IV) bolus followed by 0.5 mg/kg/h infusion), while xylazine was administered in both groups via a titrated infusion to effect according to the Ghent Sedation Algorithm. Sedation depth, ataxia, surgical condition scores, and cardiorespiratory parameters were recorded. Data are presented as median (25th–75th percentiles) and estimated effect with 95% confidence intervals (CI). Statistical significance was set at p < 0.05 and at 95% CIs excluding zero. The addition of ketamine did not significantly reduce xylazine requirements (0.9 (0.7–1.3) vs. 0.8 (0.5–1.1) mg/kg/h for SX and KX, respectively; p = 0.139). However, horses receiving ketamine (KX) achieved deeper sedation (Estimate = 2.74; 95% CI: 0.95 to 4.63) with no differences in ataxia or surgical conditions. Cardiorespiratory variables remained stable in both groups, and no adverse events occurred. In conclusion, adding a subanesthetic ketamine infusion improved sedation depth without adverse effects but did not significantly reduce the xylazine requirement. Full article
(This article belongs to the Special Issue Emerging Trends in Veterinary Anesthesia and Analgesia)
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17 pages, 1047 KB  
Article
Toward Personalized Withdrawal of TNF-α Inhibitors in Non-Systemic Juvenile Idiopathic Arthritis: Predictors of Biologic-Free Remission and Flare
by Ekaterina I. Alexeeva, Irina T. Tsulukiya, Tatyana M. Dvoryakovskaya, Ivan A. Kriulin, Dmitry A. Kudlay, Anna N. Fetisova, Maria S. Botova, Tatyana Y. Kriulina, Elizaveta A. Krekhova, Natalya M. Kondratyeva, Meiri Sh. Shingarova, Maria Y. Kokina, Alyona N. Shilova and Mikhail M. Kostik
Pharmaceuticals 2026, 19(1), 125; https://doi.org/10.3390/ph19010125 - 10 Jan 2026
Viewed by 257
Abstract
Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or [...] Read more.
Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension. Objective: We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-α inhibitor withdrawal in children with non-systemic JIA. Methods: In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. At the time of TNF-α inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg/kg every 2 weeks; adalimumab 24 mg/m2 every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg/kg weekly; adalimumab 12 mg/m2 every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse. Results: Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (≥2), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics. Conclusions: Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA. Full article
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27 pages, 2457 KB  
Article
Agent- and Dose-Specific Intestinal Obstruction Safety of GLP-1 Receptor Agonists and SGLT2 Inhibitors: A Network Meta-Analysis of Randomized Trials
by Jiann-Jy Chen, Chih-Wei Hsu, Chao-Ming Hung, Mein-Woei Suen, Hung-Yu Wang, Wei-Chieh Yang, Brendon Stubbs, Yen-Wen Chen, Tien-Yu Chen, Wei-Te Lei, Andre F. Carvalho, Shih-Pin Hsu, Yow-Ling Shiue, Bing-Yan Zeng, Cheng-Ta Li, Kuan-Pin Su, Chih-Sung Liang, Bing-Syuan Zeng and Ping-Tao Tseng
Int. J. Mol. Sci. 2026, 27(2), 608; https://doi.org/10.3390/ijms27020608 - 7 Jan 2026
Viewed by 275
Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel [...] Read more.
Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01–6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08–10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24–0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction. Full article
(This article belongs to the Special Issue Targeted Peptide Drugs for Metabolic Diseases)
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32 pages, 5015 KB  
Review
Evidence Synthesis and Mechanism Analysis of Quercetin Treatment for Atherosclerosis: A Preclinical Systematic Review and Meta-Analysis
by Daiqian Chen, Jiawei Wang, Zhiguo Lei, Liping Qu and Wenjun Zou
Int. J. Mol. Sci. 2026, 27(1), 527; https://doi.org/10.3390/ijms27010527 - 4 Jan 2026
Viewed by 378
Abstract
Atherosclerosis seriously endangers human health. Quercetin has drawn attention for its potential anti-atherosclerotic pharmacological effects. This study aimed to comprehensively assess quercetin’s effect and potential mechanism in treating atherosclerosis through a systematic review and meta-analysis. Preclinical studies published before 20 January 2025 were [...] Read more.
Atherosclerosis seriously endangers human health. Quercetin has drawn attention for its potential anti-atherosclerotic pharmacological effects. This study aimed to comprehensively assess quercetin’s effect and potential mechanism in treating atherosclerosis through a systematic review and meta-analysis. Preclinical studies published before 20 January 2025 were searched for in databases including PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP. The CAMARADES list was used to assess the quality of the included studies. Stata 12 was applied for overall effect, sensitivity, subgroup, and publication bias analyses. Time–dose interval analyses were conducted to explore how quercetin dose and dosing cycle affect intervention effects. Finally, trial sequential analyses were performed using TSA 0.9 software. A total of 22 studies involving 421 animals were included, with a mean methodological quality score of 7.73/10. Meta-analysis showed that relative to the control group, quercetin reduced aortic plaque area, adjusted lipids (lowered TC, TG, and LDL-C and raised HDL-C), downregulated adhesion factors (e.g., VCAM-1) and pro-inflammatory factors (e.g., IL-1β and IL-6), upregulated anti-inflammatory factor IL-10 and antioxidant enzymes (SOD, CAT) while decreasing MDA content, and regulated atherosclerosis-related targets (e.g., LXRα, SIRT1, and mTOR). Subgroup analyses found model establishment time and quercetin administration time affected aortic lesion areas, TC, and TG. Time–dose analysis indicated quercetin had better ameliorative effects on atherosclerosis at 25–100 mg/kg with an 8–10-week intervention. Quercetin significantly improves atherosclerosis and inhibits its occurrence and progression through multiple pathways, such as regulating lipid metabolism, anti-inflammatory effects, and counteracting oxidative stress. Based on current evidence, quercetin is a potential therapeutic agent for treating atherosclerosis. Full article
(This article belongs to the Section Molecular Pharmacology)
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