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32 pages, 34058 KB  
Article
The NeuroImmunoEndocrine Circuit of Umami Peptides: A Systems Biology Approach
by Shiva Hemmati and Abdolali Mohagheghzadeh
Nutrients 2026, 18(8), 1299; https://doi.org/10.3390/nu18081299 - 20 Apr 2026
Abstract
Background/Objectives: Umami peptides enhance flavor and contribute to appetite regulation (satiety) and metabolic health. By signaling to the orbitofrontal cortex, umami has been shown to improve cognitive function in Alzheimer’s disease dementia. This taste boosts the immune system and induces saliva secretion. [...] Read more.
Background/Objectives: Umami peptides enhance flavor and contribute to appetite regulation (satiety) and metabolic health. By signaling to the orbitofrontal cortex, umami has been shown to improve cognitive function in Alzheimer’s disease dementia. This taste boosts the immune system and induces saliva secretion. However, the molecular mechanisms linking umami peptides to systemic physiology remain poorly understood. This study provides the first integrated analysis of neurological, immunological, and endocrinological pathways activated by umami peptides. Methods: Novel umami peptides were identified using machine-learning and deep-learning analyses from a library of marine-derived bioactive peptides. T1R1-T1R3 heterodimer is the dominant receptor for umami taste transmission in humans, expressed on taste cells, intestinal cells, and hypothalamic tanycytes. Molecular docking confirmed the binding of novel ligands to the T1R1-T1R3 receptor complex. New candidates and experimentally validated umami peptides, identified by sensomics approaches from tauco, chicken soup, pufferfish, and dry-cured ham, were analyzed using gene ontology. Results: The functional enrichment analysis revealed crosstalk among key signaling processes, including glutamatergic and opioidergic pathways. In addition to the role of µ1 opioid receptor (OPRM1), hub gene intersections highlight cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and the anorexigenic pro-opiomelanocortin (POMC) neurons as potential regulators of the gut–brain axis in satiety signaling. Chemokine-encoding genes, melanin-concentrating hormone (MCH), oxytocin (OXT), and neurotensin (NTS) were other key target genes. Conclusions: The identified targets reveal the coordinated crosstalk between peripheral and central umami signaling that may contribute to the regulation of feeding behavior, satiety, cognition, memory, learning, and immune function. These network-based insights generate hypotheses and guide the design of nutritional and drug-like effectors for metabolic and cognitive health. Full article
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14 pages, 278 KB  
Article
Out of Sight: Sex Differences in Public and Semi-Public Drug Use Settings Among People Who Use Opioids in Baltimore, Maryland
by Carl A. Latkin, Lauren Dayton, Ananya Bhaktaram, Melissa A. Davey-Rothwell, Haley Bonneau, Grace Tian Yi and Oluwaseun Falade-Nwulia
Int. J. Environ. Res. Public Health 2026, 23(4), 534; https://doi.org/10.3390/ijerph23040534 - 20 Apr 2026
Abstract
Background: Drug use settings are critical determinants of overdose risk and other drug-related harms. Although sex differences in drug use patterns are well documented, less is known about sex differences in the types of locations where people use drugs. This study examined sex [...] Read more.
Background: Drug use settings are critical determinants of overdose risk and other drug-related harms. Although sex differences in drug use patterns are well documented, less is known about sex differences in the types of locations where people use drugs. This study examined sex differences in drug use settings among people who use opioids. Methods: Data were from the baseline survey of the OASIS project, a community-based study conducted in Baltimore, Maryland (N = 869), focusing on 9 specific types of locations where participants reported drug use in the past 30 days: their own residence, someone else’s residence, street, alley, park, abandoned building, public restroom, car, and other locations. Bivariate and multivariable logistic regression models examined associations between sex and drug use settings, adjusting for age, race, education, homelessness, and frequency of drug use. Results: The sample included 346 women and 523 men. In adjusted models, women had significantly lower odds than men of using drugs on the street (aOR = 0.49, 95% CI 0.35–0.70), in alleys (aOR = 0.50, 95% CI 0.35–0.69), parks (aOR = 0.57, 95% CI 0.42–0.78), abandoned buildings (aOR = 0.53, 95% CI 0.38–0.75), cars (aOR = 0.55, 95% CI 0.41–0.73), and other locations (aOR = 0.59, 95% CI 0.37–0.94). Sex was not significantly associated with drug use at one’s own residence or someone else’s residence. Conclusions: Women who use opioids were significantly less likely than men to use drugs in public and semi-public settings, which may reflect gendered patterns of stigma, interpersonal violence, and safety concerns. Harm reduction programs should focus on making current drug use settings safer and developing additional safer settings with an emphasis on addressing barriers for women to access harm reduction services, including women-centered overdose prevention centers and household-based overdose response training. Full article
(This article belongs to the Section Behavioral and Mental Health)
13 pages, 1245 KB  
Article
Analgesic Use in Patients with Mild Inflammatory Bowel Disease—A Nationwide Cohort Study Based on Prescription Data
by Bente Mertz Nørgård, Caroline Theilgaard Thorarinsson, Kevin Erichsen Zeiss, Rahul S. Dalal, Mette Louise Andersen, Ken Lund, Sonia Friedman, Jens Kjeldsen and Torben Knudsen
J. Clin. Med. 2026, 15(8), 3121; https://doi.org/10.3390/jcm15083121 - 20 Apr 2026
Abstract
Background: In patients with Crohn’s disease (CD) and ulcerative colitis (UC) disease severity and activity have been associated with pain. Data on analgesic use in patients with mild disease, however, are limited. We examined prescribed analgesics in mild CD and UC. Methods: In [...] Read more.
Background: In patients with Crohn’s disease (CD) and ulcerative colitis (UC) disease severity and activity have been associated with pain. Data on analgesic use in patients with mild disease, however, are limited. We examined prescribed analgesics in mild CD and UC. Methods: In this cohort study, based on nationwide Danish prescription data, we identified incident patients (1996 through 2020) with mild CD (N = 5348) and UC (N = 15,622). Mild disease was defined by absence of advanced medical treatments, and no surgeries, in the period of 3.5 years after the diagnosis. We examined opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and paracetamol. We also examined opioid use in CD compared to UC. Results: In mild CD, the proportions of patients using analgesics in 2001 and 2020 were: strong/weak opioids 9.1% and 10.0%, chronic opioids 3.2% and 4.1%, NSAIDs 12.4% and 8.5%, and paracetamol 4.0% and 21.7%, respectively. In mild UC, the corresponding proportions in 2001 and 2020 were: strong/weak opioids 6.2% and 7.2%, chronic opioids 2.9% and 2.7%, NSAIDs 12.7% and 8.3%, and paracetamol 2.4% and 19.5%, respectively. The adjusted OR for chronic opioid use in mild CD relative to mild UC was 1.61 (95% CI 1.41–1.85). Conclusions: We found a widespread use of prescribed analgesics in patients with mild IBD. The trends across two decades were similar for both diseases: a steep increase in paracetamol, a modest decline in NSAIDs, a slight decline in weak opioids, but no decline in strong opioids. The risk of chronic opioid use was higher in mild CD than in mild UC. We suggest that patients with mild disease may have pain issues that need to be managed clinically. Full article
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14 pages, 1617 KB  
Review
Synaptic Plasticity as a Mechanism of Opioid Tolerance and Hyperalgesia
by Fenfen Qin, Qisheng Wang, Salahadin Abdi and Lingyong Li
Biology 2026, 15(8), 640; https://doi.org/10.3390/biology15080640 - 18 Apr 2026
Viewed by 87
Abstract
Opioid analgesics are essential in the management of severe and chronic pain; however, their prolonged use is limited by the onset of analgesic tolerance and opioid-induced hyperalgesia (OIH). Recent studies increasingly implicate both synaptic functional and structural plasticity within nociceptive pathways as crucial [...] Read more.
Opioid analgesics are essential in the management of severe and chronic pain; however, their prolonged use is limited by the onset of analgesic tolerance and opioid-induced hyperalgesia (OIH). Recent studies increasingly implicate both synaptic functional and structural plasticity within nociceptive pathways as crucial mechanisms in OIH and tolerance. This review integrates current mechanistic understanding of how opioids alter synaptic transmission throughout the dorsal root ganglia (DRG), spinal dorsal horn, and supraspinal nociceptive networks. Peripherally, μ-opioid receptor (MOR) activation on TRPV1-positive nociceptors initiates presynaptic long-term potentiation (LTP), forming an early substrate for central sensitization. In the spinal dorsal horn, chronic opioid exposure drives NMDAR-dependent LTP, TRPC-mediated calcium influx, and actin cytoskeleton remodeling, leading to persistent increases in synaptic strength and excitatory connectivity. In supraspinal regions—including the ventral hippocampus, prefrontal cortex, and amygdala—opioids promote experience-dependent plasticity and predictive coding, which link environmental cues to reduced analgesic effectiveness. In addition to synaptic functional plasticity, opioid-induced synaptic structural plasticity within nociceptive pathways has been shown to underlie the long-term nature of opioid analgesic tolerance. Collectively, these data define a distributed network of opioid-responsive synapses whose pathological potentiation underpins the development of tolerance and hyperalgesia. Elucidating these mechanisms underlying OIH and tolerance paves the way for targeted therapeutic strategies that maintain analgesic efficacy while minimizing adverse synaptic remodeling and negative outcomes. Full article
(This article belongs to the Section Neuroscience)
19 pages, 747 KB  
Article
A Practical Framework for Wastewater-Based Monitoring of Substance Use in Public Health Settings
by Shisbeth Tabora-Sarmiento, Thomas D. Sinkway, Sarah E. Robinson, Francisco Paneque, Nicole Winn, Jeantel Cheramy, Linda B. Cottler, John A. Bowden, Tara Sabo-Attwood and Joseph H. Bisesi
Int. J. Environ. Res. Public Health 2026, 23(4), 518; https://doi.org/10.3390/ijerph23040518 - 17 Apr 2026
Viewed by 196
Abstract
The ongoing substance use crisis in the United States involves a broad range of illicit and prescription drugs, including opioids, stimulants, sedatives, and various psychoactive and non-psychoactive compounds. Traditional surveillance methods rely on self-reported data, which could lead to bias and recall inconsistencies. [...] Read more.
The ongoing substance use crisis in the United States involves a broad range of illicit and prescription drugs, including opioids, stimulants, sedatives, and various psychoactive and non-psychoactive compounds. Traditional surveillance methods rely on self-reported data, which could lead to bias and recall inconsistencies. Wastewater-based epidemiology has emerged as a powerful, non-invasive tool for monitoring community-level drug use, offering near real-time estimates and the potential to serve as an early warning system. However, challenges such as analyte degradation, wastewater variability, and matrix effects can affect data quality and comparability across regions. This study presents a standardized, practical workflow for multi-drug (n = 52) detection in wastewater, aiming to minimize analyte loss and improve reproducibility. Composite samples were collected from multiple U.S. cities, transported on ice, and extracted using solid-phase extraction. Extraction efficiencies were compared using Oasis Hydrophilic-Lipophilic-Balanced and Mixed-mode Cation-Exchange (MCX) cartridges, with the MCX sorbent providing complementary reversed-phase and cation-exchange interactions that enabled the retention of chemically diverse compounds across multiple drug classes. Analysis was performed with an Ultra-High-Performance Liquid Chromatography system coupled to a triple quadrupole mass spectrometer, in which the instrument parameters and critical methodological considerations, including sample handling, transport, column selection, and method validation, are detailed. This work contributes to the development of a robust, scalable protocol for multi-drug surveillance in wastewater, supporting timely, data-driven public health responses and informing national drug policy efforts. Full article
(This article belongs to the Section Environmental Sciences)
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21 pages, 1446 KB  
Review
Constipation in Older Adults: Pathophysiology, Clinical Impact, and Management Strategies
by Shima Mimura, Asahiro Morishita, Atsuo Kitaoka, Kota Sasaki, Hiroki Tai, Rie Yano, Mai Nakahara, Kyoko Oura, Tomoko Tadokoro, Koji Fujita, Joji Tani, Takashi Himoto and Hideki Kobara
Geriatrics 2026, 11(2), 47; https://doi.org/10.3390/geriatrics11020047 - 16 Apr 2026
Viewed by 312
Abstract
Background/Objectives: Constipation is a common gastrointestinal problem in older adults and is associated with reduced quality of life, functional decline, frailty, and an increased risk of delirium and cognitive impairment. Its pathogenesis is multifactorial, involving age-related changes in gastrointestinal motility, neural regulation, comorbidities, [...] Read more.
Background/Objectives: Constipation is a common gastrointestinal problem in older adults and is associated with reduced quality of life, functional decline, frailty, and an increased risk of delirium and cognitive impairment. Its pathogenesis is multifactorial, involving age-related changes in gastrointestinal motility, neural regulation, comorbidities, and polypharmacy. However, this condition has traditionally been regarded as a localized gastrointestinal disorder, which may not fully reflect its systemic clinical significance in older populations. While prior narrative reviews have described multifactorial contributors to constipation, none have formally applied a geriatric syndrome framework to integrate these dimensions. This review proposes a three-criterion operational definition—multifactorial pathogenesis, association with functional decline and frailty, and contribution to adverse systemic outcomes—to characterize constipation in older adults as a “systemic geriatric syndrome,” and evaluates available evidence against each criterion. Methods: A narrative literature search was conducted using PubMed to identify relevant studies published between 1 January 2023, and 31 December 2025. MeSH terms included “Constipation” [Major Topic] and “Aged” [MeSH Terms]. Eligible articles included English-language original studies, systematic reviews, and clinical or epidemiological studies involving individuals aged ≥65 years. Results: Diagnosis in older adults is often complicated by secondary causes, including medications and neurological disorders, as well as atypical symptom presentations in individuals with cognitive impairment. Key pathophysiological mechanisms include reductions in interstitial cells of Cajal, impaired smooth muscle contractility, dysfunction of the enteric and autonomic nervous systems, and gut microbiota dysbiosis, which may promote chronic low-grade inflammation. Major contributing factors include physical inactivity, sarcopenia, dehydration, inappropriate defecation posture, and polypharmacy, particularly opioids and anticholinergic agents. Importantly, these factors interact through the brain–gut–microbiota axis, contributing not only to gastrointestinal dysfunction but also to systemic outcomes such as frailty, cognitive decline, and increased healthcare burden, thereby supporting a multidimensional disease framework. Conclusions: The available evidence collectively supports the plausibility of framing constipation in older adults as a systemic geriatric syndrome, though formal validation of this classification requires further longitudinal and mechanistic research. Comprehensive and individualized management strategies, extending beyond simple laxative use, are essential to reduce complications and preserve functional health in aging populations. Further studies are required to validate this framework. Full article
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27 pages, 1576 KB  
Article
Synthesis of 4-Hydroxyphenylamino-Naphthoquinones as Paracetamol-Inspired Analogs: Chemical, In Silico, and Phenotypic Pharmacological Evaluation
by Iván M. Quispe-Díaz, Oswaldo Rebaza-Rioja, Sussan Lopez-Mercado, Cinthya Enriquez-Lara, Daniel Asunción-Alvarez, Roberto O. Ybañez-Julca, Elena Mantilla-Rodríguez, Wilfredo O. Gutiérrez-Alvarado, Ricardo Pino-Rios, Jaime A. Valderrama and Julio Benites
Pharmaceutics 2026, 18(4), 482; https://doi.org/10.3390/pharmaceutics18040482 - 14 Apr 2026
Viewed by 327
Abstract
Background/Objectives: Paracetamol is a widely analgesic and antipyretic drug; however, its limited anti-inflammatory efficacy and safety concerns motivate the search for novel non-opioid alternatives. In this study, a series of 4-hydroxyphenylamino-naphthoquinones were designed as paracetamol-inspired analogs and synthesized via a solvent-free, silica-assisted [...] Read more.
Background/Objectives: Paracetamol is a widely analgesic and antipyretic drug; however, its limited anti-inflammatory efficacy and safety concerns motivate the search for novel non-opioid alternatives. In this study, a series of 4-hydroxyphenylamino-naphthoquinones were designed as paracetamol-inspired analogs and synthesized via a solvent-free, silica-assisted Michael addition, providing a sustainable and efficient synthetic route. Methods: The compounds were evaluated using an integrated strategy combining in silico prediction, density functional theory calculations, molecular docking, ADMET profiling, and in vivo phenotypic pharmacological assays. Results: In vivo evaluation revealed pronounced peripheral antinociceptive activity in the acetic acid-induced writhing model and robust anti-inflammatory effects in carrageenan-induced paw edema, comparable to those of naproxen. These findings suggest a predominantly peripheral mechanism consistent with anti-inflammatory and antinociceptive profiles linked to cyclooxygenase inhibition. A normalization-based multi-criteria analysis integrating peripheral, anti-inflammatory, central, and antipyretic endpoints enabled transparent phenotypic prioritization within the series. Under this framework, compound 7 emerged as the most balanced peripheral–anti-inflammatory candidate, whereas compound 8, evaluated experimentally as a regioisomeric mixture, showed comparatively stronger central antinociceptive activity in the hot plate test. Antipyretic activity in an LPS-induced fever model was limited and not sustained. Conclusions: Overall, these findings indicated that the 4-hydroxyphenylamino-naphthoquinone scaffold emerges as a promising non-opioid platform for peripheral inflammatory pain, supporting further investigation of its pharmacological and mechanistic properties. Full article
(This article belongs to the Section Drug Targeting and Design)
8 pages, 196 KB  
Article
Acute Pancreatitis in Pregnancy and the Early Postpartum Period: An Anaesthesiology and Critical Care Perspective
by Krisztina Tóth, Zsombor Márton, Csaba Csontos and Sándor Márton
J. Clin. Med. 2026, 15(8), 2968; https://doi.org/10.3390/jcm15082968 - 14 Apr 2026
Viewed by 255
Abstract
Background/Objectives: Acute pancreatitis in pregnancy and the early postpartum period (APIP) is an uncommon but potentially life-threatening condition associated with significant maternal morbidity. Physiological adaptations of pregnancy, recent obstetric surgery, and overlapping postoperative symptoms frequently obscure early diagnosis and complicate perioperative and critical [...] Read more.
Background/Objectives: Acute pancreatitis in pregnancy and the early postpartum period (APIP) is an uncommon but potentially life-threatening condition associated with significant maternal morbidity. Physiological adaptations of pregnancy, recent obstetric surgery, and overlapping postoperative symptoms frequently obscure early diagnosis and complicate perioperative and critical care management. This review provides a clinically oriented, anaesthesiology-focused overview of APIP, integrating current evidence with perioperative decision-making, pain management strategies, and intensive care considerations relevant to obstetric practice. Methods: A narrative, clinically structured review of the literature was performed focusing on epidemiology, aetiology, diagnosis, severity stratification, and management of APIP. Anaesthesiology- and ICU-specific aspects are synthesised into a pragmatic management framework. Results: Gallstone disease and hypertriglyceridaemia remain the predominant causes of APIP, with most cases occurring in the third trimester or early postpartum period. Diagnosis relies on pancreatic enzyme elevation and pregnancy-adapted imaging strategies. Early goal-directed fluid resuscitation, effective multimodal analgesia, and timely initiation of enteral nutrition are key determinants of outcome. Therapeutic ERCP and laparoscopic cholecystectomy can be safely performed during pregnancy when clinically indicated and may reduce recurrence in biliary pancreatitis. Neuraxial analgesia provides effective, opioid-sparing pain control and may improve respiratory mechanics and haemodynamic stability. Persistent organ failure remains the strongest predictor of adverse outcome and should prompt early intensive care admission. Conclusions: APIP requires early recognition and severity-adapted, multidisciplinary management. Anaesthesiology-led strategies play a central role in optimising analgesia, haemodynamic stability, and timely escalation of care. Framing APIP within a perioperative and critical care context may improve maternal outcomes in this vulnerable patient population. Full article
(This article belongs to the Section Anesthesiology)
11 pages, 655 KB  
Article
Comparison of the Effectiveness of Interscalene Nerve Block and Serratus Posterior Superior Intercostal Plane Block in Patients Undergoing Arthroscopic Shoulder Surgery
by Omer Doymus, Ela Nur Medetoglu, Habip Burak Ozgodek, Ozlem Dilara Erguney, Pelin Aydın, Nasuhi Altay, Aslı Turgut and Ali Ahiskalioglu
Healthcare 2026, 14(8), 1028; https://doi.org/10.3390/healthcare14081028 - 14 Apr 2026
Viewed by 203
Abstract
Background/Objectives: Shoulder arthroscopies are commonly conducted in orthopedic practice. The interscalene brachial plexus block (ISB) is regarded as the “gold standard” for postoperative analgesia in shoulder surgeries. The serratus posterior superior intercostal plane block (SPSIPB) was introduced as an innovative treatment for [...] Read more.
Background/Objectives: Shoulder arthroscopies are commonly conducted in orthopedic practice. The interscalene brachial plexus block (ISB) is regarded as the “gold standard” for postoperative analgesia in shoulder surgeries. The serratus posterior superior intercostal plane block (SPSIPB) was introduced as an innovative treatment for addressing thoracic and shoulder discomfort. This study aims to examine the effects of SPSIPB and ISB techniques on postoperative pain levels, opioid intake, and respiratory function measures in patients having shoulder arthroscopy. Methods: Patients were divided into two groups. In the ISB group, 15 mL of fluid containing 0.25% bupivacaine was applied between interscalene muscles, while in the SPSIPB group, 30 mL of 0.25% bupivacaine was applied in the fascial plane between the serratus posterior superior muscle and the intercostal muscles. Results: There were no statistically significant differences in demographic characteristics (p > 0.05). VAS scores were statistically lower in the ISB group compared to the SPSIPB group at rest at 1, 2, 4, 8, 12, and 24 h postoperatively in the PACU (p < 0.05). VAS scores were also lower in the ISB group compared to the SPSIPB group during active movement at 1, 2, 4, 8, and 12 h postoperatively in the PACU (p < 0.05). Twenty-four-hour fentanyl consumption was lower in the ISB group compared to the SPSIPB group (407.50 ± 169.32 μg and 767.50 ± 178.00 μg, respectively, p < 0.001). The decrease in FEV1 and FVC was higher in the ISB group compared to the SPSIPB group (p < 0.001). Conclusions: ISB effectively relieves pain during shoulder arthroscopic procedures; however, while SPSIPB is considered a more advantageous option in terms of respiratory safety, it may not provide adequate analgesia on its own. Full article
(This article belongs to the Section Clinical Care)
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19 pages, 1335 KB  
Article
A Comprehensive HPLC-HRMS/MS Targeted Screening Method to Detect 90 New Psychoactive Substances in Oral Fluid Samples
by Ilaria Spinella, Fabio Altieri, Simona Pichini, Adele Minutillo and Annagiulia Di Trana
Biology 2026, 15(8), 616; https://doi.org/10.3390/biology15080616 - 13 Apr 2026
Viewed by 424
Abstract
The continuous emergence of New Psychoactive Substances (NPS) poses a significant challenge to public health and forensic toxicology due to their unpredictable pharmacology and rapid turnover on the illicit market. This study describes the development and validation of a high-resolution screening method for [...] Read more.
The continuous emergence of New Psychoactive Substances (NPS) poses a significant challenge to public health and forensic toxicology due to their unpredictable pharmacology and rapid turnover on the illicit market. This study describes the development and validation of a high-resolution screening method for the simultaneous detection of 90 NPS in oral fluid (OF), a matrix of choice for non-invasive sampling and roadside testing. The analytical workflow utilizes a “dilute-and-shoot” approach (1:2 v/v dilution) followed by ultra-high-performance liquid chromatography coupled with a quadrupole-Orbitrap hybrid mass spectrometer (UHPLC-HRMS/MS). Chromatographic separation was achieved in 11 min using a biphenyl column and a gradient elution. The method was validated according to ANSI/ASB Standard 036 guidelines, covering 90 substances including synthetic cannabinoids (e.g., HHC, MDMB-4en-PINACA), synthetic cathinones, and high-risk synthetic opioids such as nitazenes and fentanyl analogues. Results showed high sensitivity, with limits of identification (LOI) reaching 1 ng/mL for 44.4% of the analytes and 5 ng/mL for 37.8%, while the remaining compounds showed higher LOIs ranging from 10 to 100 ng/mL. No significant matrix interference or carryover was observed. The method was successfully applied to real samples from external quality control programs and forensic cases. This robust and versatile screening tool is suitable for clinical and forensic applications, supporting the monitoring of emerging NPS trends. Full article
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21 pages, 1805 KB  
Article
Intraoperative Magnesium Sulfate and Early Postoperative Analgesia in Lumbar Microdiscectomy: A Retrospective Clinical Study Integrating Molecular Docking and Protein Interaction Network Analysis
by Tamer Tamdogan, Ersin Guner, Ilke Tamdogan, Sevim Ondul, Muharrem Furkan Yuzbasi, Ibrahim Yilmaz and Hanefi Ozbek
J. Clin. Med. 2026, 15(8), 2888; https://doi.org/10.3390/jcm15082888 - 10 Apr 2026
Viewed by 315
Abstract
Background: Magnesium sulfate (MgSO4) has been investigated as an adjuvant in perioperative analgesia because of its antagonistic effects on the N-methyl-D-aspartate receptor (NMDA receptor) and its potential to attenuate central sensitization. However, clinical findings regarding its analgesic efficacy remain inconsistent across [...] Read more.
Background: Magnesium sulfate (MgSO4) has been investigated as an adjuvant in perioperative analgesia because of its antagonistic effects on the N-methyl-D-aspartate receptor (NMDA receptor) and its potential to attenuate central sensitization. However, clinical findings regarding its analgesic efficacy remain inconsistent across surgical procedures. Lumbar microdiscectomy is a common spinal procedure in which effective early postoperative pain control is important for patient comfort and early mobilization. This study aimed to evaluate the effect of intraoperative MgSO4 administration on early postoperative analgesia and perioperative outcomes in patients undergoing lumbar microdiscectomy. Methods: This retrospective single-center cohort study included thirty-eight patients with American Society of Anesthesiologists (ASA) physical status I–II who underwent elective single-level lumbar microdiscectomy under general anesthesia. Patients were divided into two groups according to intraoperative magnesium administration: a control group receiving standard anesthesia without MgSO4 (n = 19) and an MgSO4 group receiving an intravenous MgSO4 bolus of 30 mg/kg followed by a continuous infusion of 10 mg/kg/h until skin closure (n = 19). Postoperative pain intensity was assessed using the Numeric Rating Scale (NRS) at 0, 5, 10, 15, and 30 min after admission to the post-anesthesia care unit. Secondary outcomes included intraoperative remifentanil consumption, extubation time, and time to first mobilization. Complementary in silico analyses included molecular docking and protein–protein interaction (PPI) network analysis. Results: Postoperative NRS scores were numerically lower in the MgSO4 group; however, between-group differences were not statistically significant. Mean intraoperative remifentanil consumption was numerically lower in the MgSO4 group (236 ± 166 µg) compared with the control group (319 ± 298 µg), without statistical significance (p = 0.27). Repeated-measures analysis demonstrated the significant effect of time on postoperative NRS scores, whereas the overall group effect was not significant. Molecular analyses indicated stable morphine binding to opioid receptors and highlighted glutamatergic signaling components as central nodes within the interaction network. Conclusions: Intraoperative MgSO4 administration was not associated with significant improvements in early postoperative pain scores or perioperative recovery parameters following lumbar microdiscectomy. Molecular analyses provide exploratory in silico insights and should be interpreted cautiously given the retrospective design and the in silico nature of these findings. Full article
(This article belongs to the Section Anesthesiology)
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19 pages, 1844 KB  
Review
Evidence Map of Pharmacologic and Non-Pharmacologic Perioperative Strategies for Managing Acute Postoperative Pain After Laparoscopic Surgery, 2012–2025: The M-PALS Collaborative
by Romil R. Parikh, Gabriella L. Lott, Miranda Considine, Peter Sawtell, Sallee Brandt, Luz Angela Choconta-Piraquive, Swathi Pagadala, Drew J. Persson, Amy M. Claussen, Christopher J. Tignanelli, Timothy Wilt, Shahnaz Sultan, Adalyn J. Scherer, Aaron Berg, Christie L. Martin, Elizabeth Wick, Genevieve B. Melton, Mary E. Butler and Bronwyn J. Southwell
J. Clin. Med. 2026, 15(8), 2872; https://doi.org/10.3390/jcm15082872 - 10 Apr 2026
Viewed by 249
Abstract
Background: Effectively managing acute postoperative pain after laparoscopic surgery (M-PALS) is essential to optimize outcomes, enhance recovery, and mitigate opioid-related risks. We aimed to systematically map evidence on effectiveness and harms of pharmacologic and non-pharmacologic interventions for M-PALS. Methods: We searched three databases [...] Read more.
Background: Effectively managing acute postoperative pain after laparoscopic surgery (M-PALS) is essential to optimize outcomes, enhance recovery, and mitigate opioid-related risks. We aimed to systematically map evidence on effectiveness and harms of pharmacologic and non-pharmacologic interventions for M-PALS. Methods: We searched three databases (2012–2025) for randomized clinical trials (RCTs) that reported postoperative opioid use and pain-related outcomes. We assessed study quality using the Cochrane Risk of Bias (ROB)-2 tool. Results: From 7638 citations, we included 101 RCTs. Postoperative opioid use was reported variably (e.g., total use over 24 or 48 h postoperatively, frequency of rescue-opioid use, and time to first rescue-opioid use). One out of 101 RCTs evaluated opioid prescription at discharge. No RCT reported opioid use at ≥3 months postoperatively. Eleven strategies were evaluated in ≥2 RCTs, with usual care/ sham as comparators. None of the 101 RCTs favored usual care over any intervention for pain or opioid use outcomes. For regional anesthesia (21 RCTs total; 12 with low ROB), intraperitoneal/preperitoneal local anesthetic instillation (10 RCTs; 4 with low ROB), intravenous dexamethasone (3 RCTs; 1 with low ROB), and the Enhanced Recovery After Surgery (ERAS) protocol (3 RCTs; 0 with low ROB), compared to usual care, >50% of RCTs favored the intervention for reducing pain and opioid use. For adverse events, only 3 out of 101 RCTs favored comparators. Inconsistent outcome reporting across all RCTs and, for multimodal strategies, the uniqueness of intervention–comparator combinations hindered comparisons. Conclusions: Interventions for M-PALS appear safe, with no RCT indicating worse efficacy of intervention than usual care; but evidence regarding superiority is conflicting. Future research should establish standardized and longer-term core outcome sets and make head-to-head comparisons between optimal strategies. Full article
(This article belongs to the Section Anesthesiology)
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13 pages, 651 KB  
Article
Adverse Pregnancy Outcomes with Co-Occurring Opioid and Stimulant Use Disorders
by Alexandra R. Schroeder, Noor Al-Hammadi, Tucker Doiron and Niraj R. Chavan
J. Clin. Med. 2026, 15(8), 2811; https://doi.org/10.3390/jcm15082811 - 8 Apr 2026
Viewed by 188
Abstract
Background/Objectives: Substance use disorder (SUD) in pregnancy is an increasingly complex public health challenge that is known to worsen maternal and neonatal outcomes. Rates of polysubstance use are steadily rising. The objective of this study was to assess the impact of co-occurring [...] Read more.
Background/Objectives: Substance use disorder (SUD) in pregnancy is an increasingly complex public health challenge that is known to worsen maternal and neonatal outcomes. Rates of polysubstance use are steadily rising. The objective of this study was to assess the impact of co-occurring opioid and stimulant use disorder on adverse pregnancy outcomes (APOs) among inpatient pregnancy hospitalizations. Methods: We conducted a cross-sectional analysis of inpatient pregnancy hospitalizations for delivery admissions from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) from 2016 to 2020. ICD-10 codes were used to identify patients with opioid and stimulant use disorder and with APOs. APO was defined as a composite to include hypertensive disorders of pregnancy, antepartum hemorrhage, postpartum hemorrhage, preterm birth, and fetal growth restriction. Multivariable logistic regression analyses were undertaken to predict the likelihood of APOs among pregnancy hospitalizations with opioid use, stimulant use, or co-occurring (opioid and stimulant) use disorders. Sociodemographic covariates, including age, race and/or ethnicity, insurance payor type, and income level, were accounted for. Results: From 2016 to 2020, 32,602 delivery hospitalizations complicated by stimulant or opioid use disorder were identified. Of these admissions, 21,049 (64.6%) had opioid use disorder, 9472 (29.1%) had stimulant use disorder, and 2081 (6.4%) had co-occurring opioid and stimulant use disorder. In the entire cohort, the prevalence of APOs was significantly highest among pregnancy delivery hospitalizations with co-occurring opioid use and stimulant use disorder (1136/2081—54.6%, p < 0.001), as compared with opioid use disorder (8923/21,049—42.4%) or stimulant use disorder alone (4654/9472—49.1%). Rates of APOs increased in subsequent years for all cohort groups. Adjusting for relevant sociodemographic covariates, co-occurring opioid and stimulant use disorder was an independent predictor of APO (aOR 3.65; CI 95%, 3.34–3.99). In comparison, opioid use disorder and stimulant use disorder were independent predictors of APOs with a less strong correlation, aOR 2.22 (CI 95%, 2.16–2.29) and aOR 2.89 (CI 95%, 2.77–3.02), respectively. Conclusions: Patients with co-occurring opioid and stimulant use disorder have the highest exposure risk for APOs, acting as an independent predictor for APOs when adjusting for sociodemographic covariates. Full article
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21 pages, 4959 KB  
Article
GC-MS Guided Phytochemical Fingerprinting and Multi-Target Therapeutic Evaluation of Ixora chinensis Lam. Leaves: Insights into Its Hypoglycemic and Analgesic Activities
by Joy Baisnab, Md. Saiful Islam, Md Reduanul Haque Kavey, S. M. Yasin Shourav, Md. Riaz Hosen, Md. Faysal Abid, Shaikh Shahinur Rahman, Anuwatchakij Klamrak, Arunrat Chaveerach, Sakda Daduang and Md. Rasul Karim
Biology 2026, 15(8), 592; https://doi.org/10.3390/biology15080592 - 8 Apr 2026
Viewed by 1032
Abstract
Ixora chinensis Lam. has traditionally been used to treat conditions such as acne, high blood pressure, bleeding, tuberculosis, and rheumatism. This study aimed to investigate the methanolic extract of I. chinensis leaves to determine their bioactive compounds and evaluate their effects on both [...] Read more.
Ixora chinensis Lam. has traditionally been used to treat conditions such as acne, high blood pressure, bleeding, tuberculosis, and rheumatism. This study aimed to investigate the methanolic extract of I. chinensis leaves to determine their bioactive compounds and evaluate their effects on both central and peripheral pain using in vivo and in silico approaches. The GC-MS analysis revealed 41 phytochemicals, including 14 phenolics, 4 esters, 12 terpenoids, 8 alkaloids, and 3 sulfur-containing compounds. In the glucose tolerance test, both the chloroform-soluble fraction (CF) and n-hexane fraction (NHF) exhibited p < 0.05 reductions in blood glucose levels at a dosage of 400 mg/kg with decreases of 51.94% and 46.63%, respectively, compared to the positive control (64.02%). The central analgesic evaluation showed significant (p < 0.001) enhancements in tail-flick latency for the fraction (184.94%) and CF (170.51%) following 90 min. In the pain relief assay, NHF showed inhibition (64.33%, p < 0.001) followed by an aqueous fraction (57.35%). These pharmacological findings were supported by in silico analysis. Concerning activity, 5-(dimethylamino)-1- acid phenyl ester (−8.9 kcal/mol) and 9,9-dimethyl-9H-fluoren-3-ol (−8.4 kcal/mol) displayed the strongest binding affinity to AMPK. Additionally, 2,3-diphenyl-2-cyclopropen-1-one exhibited favorable interactions with α-amylase (−8.0 kcal/mol) and α-glucosidase (−8.3 kcal/mol). Similarly, the central analgesic effect correlated with the strong μ-opioid receptor affinity of s-Triazine, 2-amino-4-(piperidinomethyl)-4-piperidino (−8.8 kcal/mol). N-Methyl-N-(4-toluenesulfonyl)-benzamide (−8.6 kcal/mol) and s-Triazine derivative (−8.9 kcal/mol) demonstrated notable COX-1 and COX-2 inhibition potential. Overall, the findings indicate I. chinensis leaves as a promising source of bioactive compounds with significant antihyperglycemic and analgesic properties. Full article
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10 pages, 376 KB  
Systematic Review
Factors Associated with Acute Colonic Pseudo-Obstruction After Cesarean Section: A Systematic Review and Meta-Analysis
by Baorong Gao, Yali Miao, Hui Ye and Rui Miao
J. Clin. Med. 2026, 15(8), 2817; https://doi.org/10.3390/jcm15082817 - 8 Apr 2026
Viewed by 234
Abstract
Objective: Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie syndrome, is a rare but serious complication following cesarean section (CS). Identifying factors associated with its occurrence is critical for early recognition and prevention. This systematic review and meta-analysis aimed to synthesize available [...] Read more.
Objective: Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie syndrome, is a rare but serious complication following cesarean section (CS). Identifying factors associated with its occurrence is critical for early recognition and prevention. This systematic review and meta-analysis aimed to synthesize available evidence on factors associated with ACPO following CS. Methods: We performed a systematic literature search across five databases (PubMed, Embase, CNKI, Wanfang, and CBM) from inception to December 2025. Studies investigating factors associated with ACPO after CS were eligible. Quality of included studies was assessed using the Newcastle–Ottawa Scale. For factors reported in at least two studies, pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated. Results: Five case-control studies comprising 484 patients (103 ACPO cases and 381 controls) were included, of which four were rated as good quality. Twenty-five potential associated factors were analyzed. Several pre-/intraoperative factors demonstrated statistically significant associations with ACPO risk, including concomitant anemia (OR = 8.94, 95% CI: 2.59–30.88), previous abdominal surgery (OR = 2.39, 95% CI: 1.28–4.47), surgery duration > 1 h (OR = 4.11, 95% CI: 2.20–7.67), and blood loss > 1000 mL (OR = 5.72, 95% CI: 2.10–15.58). Intraoperative blood loss as a continuous variable (WMD = 1.30, 95% CI: 0.14–2.46) was also significantly associated with ACPO. In contrast, emergency cesarean section, opioid use, and type of anesthesia were not significantly associated. Regarding postoperative features, bed rest > 12 h (OR = 2.66, 95% CI: 1.29–5.49), postoperative fever ≥ 38 °C (OR = 3.82, 95% CI: 1.94–7.54), elevated postoperative white blood cell count (WMD = 1.22, 95% CI: 0.30–2.14), and lower postoperative hemoglobin level (WMD = −0.50, 95% CI: −0.83 to −0.18) were significantly associated with ACPO. However, these factors may represent consequences of perioperative complications or components of the early clinical presentation of ACPO. Conclusions: This systematic review and meta-analysis identified multiple perioperative factors associated with ACPO following CS. However, the use of univariate data from a limited number of studies limits interpretability. Prospective cohort studies are needed to clarify whether these factors play a causal role in the development of ACPO. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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