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25 pages, 1564 KiB  
Review
COPD and Comorbid Mental Health: Addressing Anxiety, and Depression, and Their Clinical Management
by Rayan A. Siraj
Medicina 2025, 61(8), 1426; https://doi.org/10.3390/medicina61081426 (registering DOI) - 7 Aug 2025
Abstract
Anxiety and depression are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which can contribute to increased morbidity, reduced quality of life, and worse clinical outcomes. Nevertheless, these psychological conditions remain largely overlooked. This narrative review includes studies published between 1983 [...] Read more.
Anxiety and depression are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which can contribute to increased morbidity, reduced quality of life, and worse clinical outcomes. Nevertheless, these psychological conditions remain largely overlooked. This narrative review includes studies published between 1983 and 2025 to synthesise the current evidence on the risk factors, clinical impacts, and therapeutic strategies for these comorbidities. While the exact mechanisms leading to their increased prevalence are not fully understood, growing evidence implicates a combination of biological (e.g., systemic inflammation), social (e.g., isolation and stigma), and behavioural (e.g., smoking and inactivity) factors. Despite current guidelines recommending the identification and management of these comorbidities in COPD, they are not currently included in COPD assessments. Undetected and unmanaged anxiety and depression have serious consequences, including poor self-management, non-adherence to medications, increased risk of exacerbation and hospitalisations, and even mortality; thus, there is a need to incorporate screening as part of COPD assessments. There is robust evidence showing that pulmonary rehabilitation, a core non-pharmacological intervention, can improve mood symptoms, enhance functional capacity, and foster psychosocial resilience. Psychological therapies such as cognitive behavioural therapy (CBT), mindfulness-based approaches, and supportive counselling have also demonstrated value in reducing emotional distress and improving coping mechanisms. Pharmacological therapies, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed in moderate to severe cases or when non-pharmacological approaches prove inadequate. However, the evidence for their efficacy in COPD populations is mixed, with concerns about adverse respiratory outcomes and high discontinuation rates due to side effects. There are also barriers to optimal care, including underdiagnosis, a lack of screening protocols, limited provider training, stigma, and fragmented multidisciplinary coordination. A multidisciplinary, biopsychosocial approach is essential to ensure early identification, integrated care, and improved outcomes for patients with COPD. Full article
(This article belongs to the Special Issue Latest Advances in Asthma and COPD)
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20 pages, 5618 KiB  
Article
Age-Related Mitochondrial Alterations Contribute to Myocardial Responses During Sepsis
by Jiayue Du, Qing Yu, Olufisayo E. Anjorin and Meijing Wang
Cells 2025, 14(15), 1221; https://doi.org/10.3390/cells14151221 - 7 Aug 2025
Abstract
Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal [...] Read more.
Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal ligation and puncture (CLP) was conducted in young adult (12–18 weeks) and aged (19–21 months) male C57BL/6 mice. Cardiac function was detected 20 h post-CLP. Additionally, cardiomyocytes isolated from young adult and aged male mice were used for assessments of mitochondrial respiratory function +/– TNFα or LPS. Protein levels of oxidative phosphorylation (OXPHOS), NADPH oxidase (NOX)2, NOX4, phosphor-STAT3 and STAT3 were determined in mouse hearts 24 h post-CLP and in cardiomyocytes following inflammatory stimuli. CLP significantly reduced cardiac contractility in both young and aged mice, with a higher incidence and greater severity of cardiac functional depression in the older group. Mitochondrial respiratory capacity was decreased in cardiomyocytes derived from aged mice, with increased susceptible to inflammatory toxic effects compared to those from young adult mice. The age-dependent changes were observed in myocardial OXPHOS complexes and NOX4. Importantly, CLP led to a significant increase in OXPHOS protein levels in the hearts of older mice, suggesting a possible compensatory response to decreased mitochondrial metabolic function and a greater potential for reactive oxygen species (ROS) generation. Our findings highlight that the response of aging-impaired mitochondria to inflammation may underlie the worsened cardiac functional depression in the aged group during sepsis. Full article
(This article belongs to the Section Cellular Aging)
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24 pages, 1028 KiB  
Review
Molecular Links Between Metabolism and Mental Health: Integrative Pathways from GDF15-Mediated Stress Signaling to Brain Energy Homeostasis
by Minju Seo, Seung Yeon Pyeon and Man S. Kim
Int. J. Mol. Sci. 2025, 26(15), 7611; https://doi.org/10.3390/ijms26157611 - 6 Aug 2025
Abstract
The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact [...] Read more.
The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article
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17 pages, 307 KiB  
Article
The Use of Heart Rate Variability-Biofeedback (HRV-BF) as an Adjunctive Intervention in Chronic Fatigue Syndrome (CSF/ME) in Long COVID: Results of a Phase II Controlled Feasibility Trial
by Giulia Cossu, Goce Kalcev, Diego Primavera, Stefano Lorrai, Alessandra Perra, Alessia Galetti, Roberto Demontis, Enzo Tramontano, Fabrizio Bert, Roberta Montisci, Alberto Maleci, Pedro José Fragoso Castilla, Shellsyn Giraldo Jaramillo, Peter K. Kurotschka, Nuno Barbosa Rocha and Mauro Giovanni Carta
J. Clin. Med. 2025, 14(15), 5363; https://doi.org/10.3390/jcm14155363 - 29 Jul 2025
Viewed by 714
Abstract
Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for [...] Read more.
Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Methods: Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (quasirandom assignment). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. Results: The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, p = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, p < 0.0001). Conclusions: HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID. Full article
13 pages, 1538 KiB  
Article
Respiratory and Cardiovascular Activity of LENART01, an Analgesic Dermorphin–Ranatensin Hybrid Peptide, in Anesthetized Rats
by Piotr Wojciechowski, Dominika Zając, Adrian Górski, Wojciech Kamysz, Patrycja Kleczkowska and Katarzyna Kaczyńska
Int. J. Mol. Sci. 2025, 26(15), 7188; https://doi.org/10.3390/ijms26157188 - 25 Jul 2025
Viewed by 180
Abstract
Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side [...] Read more.
Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side effects continue unabated. The present study was designed to investigate the respiratory and cardiovascular effects of the hybrid peptide LENART01, which has evidenced potent antinociceptive and antimicrobial activity. This hybrid peptide, composed of N-terminally located dermorphin and C-terminal modified ranatensin pharmacophore, was tested in vivo in anesthetized rats. The main effect of LENART01 was apnea in 70% of examined animals, sighing, and a significant increase in blood pressure. Interestingly, the hybrid induced sighs less frequently than ranatensin, and apnea dependent on vagus nerve mu opioid receptor activation much less frequently and less intensely than dermorphin itself. This shows that LENART01 is a safer opioid system-related agent as compared to dermorphin for its prospective use in the treatment of pain. Full article
(This article belongs to the Special Issue Recent Progress of Opioid Research, 2nd Edition)
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24 pages, 816 KiB  
Systematic Review
Impact of Obstructive Sleep Apnea in Surgical Patients: A Systematic Review
by Ioana-Medeea Titu, Damiana Maria Vulturar, Ana Florica Chis, Alexandru Oprea, Alexandru Manea and Doina Adina Todea
J. Clin. Med. 2025, 14(14), 5095; https://doi.org/10.3390/jcm14145095 - 17 Jul 2025
Viewed by 555
Abstract
Background/Objectives: Obstructive sleep apnea is a prevalent, yet often underdiagnosed, condition characterized by recurrent upper airway obstruction during sleep, leading to significant perioperative risks in surgical patients. This systematic review aims to evaluate the incidence and impact of objectively diagnosed obstructive sleep [...] Read more.
Background/Objectives: Obstructive sleep apnea is a prevalent, yet often underdiagnosed, condition characterized by recurrent upper airway obstruction during sleep, leading to significant perioperative risks in surgical patients. This systematic review aims to evaluate the incidence and impact of objectively diagnosed obstructive sleep apnea on postoperative outcomes across various surgical specialties—including bariatric, orthopedic, cardiac, and otorhinolaryngologic surgeries—and to assess the effectiveness of preoperative screening and perioperative management strategies. Methods: A comprehensive literature search of PubMed was conducted for studies published between January 2013 and December 2024, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies involved adult surgical patients with OSA confirmed by polysomnography or respiratory polygraphy. Studies were assessed for methodological quality using the Oxford Centre for Evidence-Based Medicine Levels of Evidence framework. Results: The findings consistently indicated that obstructive sleep apnea significantly increases the risk of postoperative complications, such as respiratory depression, atrial fibrillation, acute kidney injury, delirium, and prolonged hospital stay. Continuous positive airway pressure therapy demonstrated a protective effect in bariatric and cardiac surgeries, though its effectiveness in orthopedic and otorhinolaryngologic contexts was inconsistent, largely due to adherence variability and limited implementation. Preoperative screening tools such as the STOP-BANG questionnaire were widely used, but their utility depended on integration with confirmatory diagnostics. Conclusions: Obstructive sleep apnea represents a significant, modifiable risk factor in surgical populations. Preoperative identification and risk-adapted perioperative management, including CPAP therapy and multimodal analgesia, may substantially reduce postoperative morbidity. However, further randomized trials and cost-effectiveness studies are needed to optimize care pathways and ensure consistent implementation across surgical disciplines. Full article
(This article belongs to the Section Respiratory Medicine)
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12 pages, 439 KiB  
Article
Non-Invasive Capnography Versus Pulse Oximetry for Early Detection of Respiratory Depression During Pediatric Procedural Sedation: A Prospective Observational Study
by Laura Català Altarriba, Sean Yeh Hsi, Aude Marie Ravit, Sònia Brió Sanagustín and Xoan González-Rioja
Children 2025, 12(7), 938; https://doi.org/10.3390/children12070938 - 16 Jul 2025
Viewed by 310
Abstract
Background/Objectives: Continuous ventilation monitoring during pediatric sedation is essential, as respiratory depression may occur silently and may not be detected promptly by conventional methods such as pulse oximetry. Non-invasive capnography has been proposed to improve early detection of respiratory compromise. This prospective observational [...] Read more.
Background/Objectives: Continuous ventilation monitoring during pediatric sedation is essential, as respiratory depression may occur silently and may not be detected promptly by conventional methods such as pulse oximetry. Non-invasive capnography has been proposed to improve early detection of respiratory compromise. This prospective observational study evaluated the diagnostic accuracy of non-invasive capnography, compared to pulse oximetry, for detecting respiratory depression in pediatric patients undergoing sedation. Methods: We conducted a single-center, prospective observational study at a tertiary pediatric hospital, enrolling 101 patients (ages 1–17 years) undergoing sedation for diagnostic or therapeutic procedures. Patients were monitored using both pulse oximetry and non-invasive capnography. Episodes of respiratory depression—defined as apnea, hypopneic hypoventilation, bradypneic hypoventilation, and desaturation—were recorded. We compared the diagnostic performance and time to detection between capnography and pulse oximetry. Results: We identified 93 episodes of respiratory depression in 52 patients (51.1%). Capnography detected all apnea episodes and 76.9% of hypopneic hypoventilation episodes that were not identified by pulse oximetry. The median time advantage of capnography over pulse oximetry was 35 s (p = 0.0055). Combining capnography and pulse oximetry identified more events than pulse oximetry alone (93 vs. 53 episodes). Conclusions: Non-invasive capnography improves the early detection of respiratory depression compared to conventional monitoring with pulse oximetry in pediatric procedural sedation. While these findings support its routine use to enhance patient safety, larger multicenter studies are needed to demonstrate its diagnostic accuracy and impact on clinical outcomes. Full article
(This article belongs to the Section Pediatric Anesthesiology, Pain Medicine and Palliative Care)
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12 pages, 1253 KiB  
Article
The Feasibility of a Music Therapy Respiratory Telehealth Protocol on Long COVID Respiratory Symptoms
by Jingwen Zhang, Joanne V. Loewy, Lisa Spielman, Zijian Chen and Jonathan M. Raskin
COVID 2025, 5(7), 107; https://doi.org/10.3390/covid5070107 - 10 Jul 2025
Viewed by 1550
Abstract
Objective: This study aims to investigate the feasibility of an online music therapy protocol for individuals previously diagnosed with COVID-19, focusing on their perceptions of their respiratory symptoms and the intervention’s impact on psychosocial measures. Methods: A within-subject experimental design was applied to [...] Read more.
Objective: This study aims to investigate the feasibility of an online music therapy protocol for individuals previously diagnosed with COVID-19, focusing on their perceptions of their respiratory symptoms and the intervention’s impact on psychosocial measures. Methods: A within-subject experimental design was applied to examine an eight-week weekly online music therapy protocol, including singing, wind instrument playing, and music visualizations. All self-report data were collected bi-weekly throughout the 16-weeks study period, including baseline and post-tests. The measures for respiratory symptoms included the Medical Research Council’s Dyspnea Scale (MRC Dyspnea), Chronic Respiratory Questionnaire-Mastery Scores (CRQ Mastery), and Visual Analogue Scale for breathlessness. The measures for the secondary psychosocial outcomes were the Beck Depression Inventory-Short Form, the Generalized Anxiety Disorder 7-item, the Hospital Anxiety and Depression Scale, the Fatigue Severity Scale, the Epworth Sleepiness Scale, the EuroQol 5-Dimension 5-Level, and the Connor-Davidson Resilience Scale. Results: Twenty-four participants were enrolled. The participants perceived a reduction in respiratory symptoms, and shortness of breath (MRC Dyspnea). Planned comparisons showed significant decreases in MRC from baseline to post-treatment (p = 0.008). The mixed-effects model, including pre-baseline and post-treatment, was significant (p < 0.001). Significant changes in Breathing VAS were consistent with improvements in MRC Dyspnea, showing a significant baseline-to-post difference (p = 0.01). The CRQ Mastery showed significant improvements from baseline to Week 12 (p < 0.001). No significant changes were observed in other secondary measures. Conclusions: Our preliminary findings suggest that this protocol is feasible, and as a result, may help individuals previously diagnosed with COVID-19 to cope with lasting respiratory symptoms and improve their perception of shortness of breath. Live music-making, including playing accessible wind instruments and singing, may contribute to an increase sense of control over breathing. As this was a feasibility study, we conducted multiple uncorrected statistical comparisons to explore potential effects. While this approach may increase the risk of Type I error, the findings are intended to inform hypotheses for future confirmatory studies rather than to draw definitive conclusions. Full article
(This article belongs to the Section Long COVID and Post-Acute Sequelae)
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16 pages, 1969 KiB  
Article
Thirteen-Year Sequelae of Marburg Virus Disease Survival: Persistent Cardiometabolic, Immunometabolic, and Haematological Alterations in the Absence of Psychological Morbidity
by Jennifer Serwanga, Raymond Ernest Kaweesa, Joseph Katende Ssebwana, Goeffrey Odoch, Raymond Reuel Wayesu, Anne Daphine Ntabadde, Deborah Mukisa, Peter Ejou, FiloStudy Team, Julius Julian Lutwama and Pontiano Kaleebu
Pathogens 2025, 14(7), 678; https://doi.org/10.3390/pathogens14070678 - 9 Jul 2025
Viewed by 442
Abstract
Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic [...] Read more.
Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article
(This article belongs to the Special Issue Marburg Virus)
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21 pages, 2112 KiB  
Article
Carbon Dioxide and Hemoglobin at Presentation with Hypertrophic Pyloric Stenosis—Are They Relevant? Cohort Study and Current Opinions
by Ralf-Bodo Tröbs, Hiltrud Niggemann, Grigore Cernaianu, Andreas Lipphaus and Matthias Nissen
Children 2025, 12(7), 885; https://doi.org/10.3390/children12070885 - 4 Jul 2025
Viewed by 284
Abstract
Background: Recurrent vomiting in infantile hypertrophic pyloric stenosis (IHPS) leads to metabolic alkalosis and a respiratory-driven compensatory hypercapnia. Alkalosis has been identified as the main causal factor for respiratory depression on admission. The value of contribution of hemoglobin and carbon dioxide partial pressure [...] Read more.
Background: Recurrent vomiting in infantile hypertrophic pyloric stenosis (IHPS) leads to metabolic alkalosis and a respiratory-driven compensatory hypercapnia. Alkalosis has been identified as the main causal factor for respiratory depression on admission. The value of contribution of hemoglobin and carbon dioxide partial pressure to this phenomenon will be evaluated. Materials and Methods: A retrospective cohort study was conducted on 105 infants with IHPS. The acid/base status, including levels of hemoglobin and lactate, were recorded. Statistical comparisons, correlation analysis, linear regression and multivariate regression analysis were applied. Results: Hypercapnia was associated with hemoconcentration. We found a positive correlation was found between pCO2 and hemoglobin (p = 0.042). The multivariate linear regression analysis showed that pCO2 is dependent on hemoglobin (p = 0.002). Lactate, which is used as a marker for anaerobic glycolysis, showed no systematic correlation with pCO2. Conclusions: An increase in carbon dioxide cannot easily be attributed to a reduced transport function of carbon dioxide due to hemoglobin deficiency. Further investigation is needed to determine the extent to which low hemoglobin levels and increased pCO2 interact with hemoconcentration to contribute to respiratory problems. Full article
(This article belongs to the Special Issue Advances in Pediatric Gastroenterology)
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25 pages, 2976 KiB  
Article
Dual Opioid–Neuropeptide FF Small Molecule Ligands Demonstrate Analgesia with Reduced Tolerance Liabilities
by Marco Mottinelli, V. Blair Journigan, Samuel Obeng, Victoria L. C. Pallares, Christophe Mѐsangeau, Coco N. Kapanda, Stephen J. Cutler, Janet A. Lambert, Shainnel O. Eans, Michelle L. Ganno, Wanhui Sheng, Tamara King, Abhisheak Sharma, Catherine Mollereau, Bonnie A. Avery, Jay P. McLaughlin and Christopher R. McCurdy
Molecules 2025, 30(13), 2851; https://doi.org/10.3390/molecules30132851 - 3 Jul 2025
Viewed by 385
Abstract
Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the [...] Read more.
Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the opioid and NPFF receptors, respectively, and displayed substitution-dependent functional profiles in the [35S]GTPγS functional assay. From six compounds screened in vivo for antinociception and ability to prevent NPFF-induced hyperalgesia in mouse warm water tail withdrawal tests, compound 22b produced dose-dependent MOR-mediated antinociception with an ED50 value (and 95% confidence interval) of 6.88 (4.71–9.47) nmol, i.c.v., and also prevented NPFF-induced hyperalgesia. Meanwhile, 22b did not demonstrate the respiratory depression, hyperlocomotion, or impaired intestinal transit of morphine. Moreover, repeated treatment with 22b produced a 1.6-fold rightward shift in antinociceptive dose response, significantly less acute antinociceptive tolerance than morphine. Evaluated for microsomal stability in vitro and in vivo pharmacokinetic profile, 22b showed suitable microsomal stability paired in vivo with a large apparent volume of distribution and a clearance smaller than the hepatic flow in rats, suggesting no extra-hepatic metabolism. In conclusion, the present study confirms that dual-action opioid–NPFF ligands may offer therapeutic promise as analgesics with fewer liabilities of use. Full article
(This article belongs to the Special Issue New Strategies for Drug Development)
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17 pages, 3192 KiB  
Article
Hypoxic Status in COPD and ARDS Patients: Impact on Lipid Signature
by Camillo Morano, Aldijana Sadikovic, Michele Dei Cas, Rocco Francesco Rinaldo, Lorena Duca, Federico Maria Rubino, Michele Mondoni, Davide Chiumello, Sara Ottolenghi, Michele Samaja and Rita Paroni
Int. J. Mol. Sci. 2025, 26(13), 6405; https://doi.org/10.3390/ijms26136405 - 3 Jul 2025
Viewed by 310
Abstract
In patients with respiratory diseases, a panel of markers is often used to assess disease severity and progression. Here we test whether the serum lipid signature may surge as a reliable alternative marker to monitor systemic hypoxia, a frequent unfavourable outcome in acute [...] Read more.
In patients with respiratory diseases, a panel of markers is often used to assess disease severity and progression. Here we test whether the serum lipid signature may surge as a reliable alternative marker to monitor systemic hypoxia, a frequent unfavourable outcome in acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary diseases (COPD). We recruited 9 healthy controls, 10 COPD patients, and 10 ARDS patients. Various markers related to inflammation, redox imbalance, and iron handling were measured alongside lipid profiles obtained through untargeted lipidomic analysis. The results show that serum lipids were moderately lower in COPD patients and significantly reduced in ARDS patients compared to the controls. Six lipid classes (cholesteryl esters, coenzyme Q, phosphatidylinositol, sterols, hexosylceramides, and phosphatidylethanolamine) exhibited significant changes (ANOVA p < 0.05) and correlated with the Horowitz index (P/F), suggesting their potential as markers of hypoxia severity. While conventional markers also correlated with P/F, the lipid signature was more specific and reliable. This study highlights that hypoxia in pulmonary diseases depresses circulating lipids, with certain lipid classes offering more precise predictions of hypoxia severity. Expanding this research to larger populations could support the lipid signature as a clinical tool. Full article
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13 pages, 573 KiB  
Article
Health-Related Quality of Life, Psychological Health, and Patient-Reported Outcomes of Amyotrophic Lateral Sclerosis Patients in China
by Dilip Dhakal, Congzhou Chen, Bo Zhang and Guanqiao Li
Brain Sci. 2025, 15(7), 696; https://doi.org/10.3390/brainsci15070696 - 28 Jun 2025
Viewed by 430
Abstract
Objectives: This study explored the health-related quality of life (HRQoL), psychological health, and patient-reported outcomes (PROs) of patients with amyotrophic lateral sclerosis (ALS) in China, providing insights for enhancing clinical care. Methods: A cross-sectional study was conducted among Chinese ALS patients between February [...] Read more.
Objectives: This study explored the health-related quality of life (HRQoL), psychological health, and patient-reported outcomes (PROs) of patients with amyotrophic lateral sclerosis (ALS) in China, providing insights for enhancing clinical care. Methods: A cross-sectional study was conducted among Chinese ALS patients between February and May 2024. Demographics, clinical characteristics, and PROs were assessed. HRQoL and psychological health were evaluated via the 5-item amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-5) and the 4-item patient health questionnaire (PHQ-4), respectively. Spearman’s rank correlation, multiple linear regression, and the Kruskal–Wallis H test were used to analyze associations between clinical factors, HRQoL, and psychological health. Results: A total of 237 participants aged 46–65 years (63.3%) were included. The mean ALSAQ-5 score was 64.86±19.34, indicating an impaired HRQoL, whereas the mean PHQ-4 score (5.82 ± 4.10,) suggested varied degree of anxiety and depression. Age, disease duration, ALS severity, fatigue, stress, and pain severity, and respiratory support were significantly associated with HRQoL (p < 0.05). Age, stress severity, and pain severity were significant predictors of psychological distress (p < 0.01). Patients reported diagnostic delay, profound lifestyle changes (96.4%), fear of paralysis (84.8%), and death (49.8%). Most patients (80.6%) expressed a strong desire to stop ALS progression, prioritizing treatments that improve breathing, muscle weakness, swallowing, and mobility issues. Conclusions: ALS profoundly impacts patients’ HRQoL and psychological health. Integrating PROs into clinical care strategies is crucial for improving patient outcomes and guiding treatment priorities. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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17 pages, 509 KiB  
Review
Respiratory Depression in Non-Operating Room Anesthesia: An Overview
by Isabel E. Royz, Nicholas B. Clevenger, Andrew Bochenek, Andrew R. Locke and Steven B. Greenberg
J. Clin. Med. 2025, 14(13), 4528; https://doi.org/10.3390/jcm14134528 - 26 Jun 2025
Viewed by 625
Abstract
Non-operating room anesthesia (NORA) is a rapidly growing domain for anesthesia professionals due to advances in procedural technology and increased emphasis on patient comfort. The majority of these procedures are conducted under monitored anesthesia care (MAC) where patients receive varying levels of sedation. [...] Read more.
Non-operating room anesthesia (NORA) is a rapidly growing domain for anesthesia professionals due to advances in procedural technology and increased emphasis on patient comfort. The majority of these procedures are conducted under monitored anesthesia care (MAC) where patients receive varying levels of sedation. Analysis of the Anesthesia Closed Claims database suggests that adverse respiratory events continue to be the main cause of morbidity and mortality in patients undergoing NORA procedures. Most NORA claims occurred under MAC, with oversedation leading to respiratory depression coupled with inadequate monitoring making up the majority of claims. The American Society of Anesthesiologists (ASA) has released standards of pre-anesthesia, intraoperative monitoring, and post-anesthesia care, which apply to all anesthetizing locations including NORA. The ASA has also made recommendations in a statement on NORA to promote patient safety. Evidence suggests that patient characteristics, monitoring tools, physical constraints, and team familiarity play a role in the risk for adverse respiratory events. Future studies are required to further understand the challenges specific to NORA locations. Full article
(This article belongs to the Section Anesthesiology)
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13 pages, 941 KiB  
Article
Effect of High-Flow Nasal Cannula vs. Facemask on Arterial Oxygenation During Liver Radiofrequency Ablation: Randomized Controlled Trial
by Jung-Pil Yoon, Go Wun Kim, Ji-Uk Yoon, Hyeonsoo Park and Kyoung-woon Joung
Medicina 2025, 61(7), 1130; https://doi.org/10.3390/medicina61071130 - 23 Jun 2025
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Abstract
Background and Objectives: Percutaneous liver radiofrequency ablation (RFA) under monitored anesthesia care (MAC) carries a risk of hypoxia due to respiratory depression. Ensuring adequate oxygenation during such procedures is essential for patient safety. This study aimed to evaluate whether a high-flow nasal [...] Read more.
Background and Objectives: Percutaneous liver radiofrequency ablation (RFA) under monitored anesthesia care (MAC) carries a risk of hypoxia due to respiratory depression. Ensuring adequate oxygenation during such procedures is essential for patient safety. This study aimed to evaluate whether a high-flow nasal cannula (HFNC) improves oxygenation compared to a simple facemask during RFA. Materials and Methods: In this prospective, randomized controlled trial, 51 patients undergoing ultrasound-guided RFA under MAC were allocated to receive oxygen via an HFNC (30 L/min) or a facemask (6 L/min). Arterial blood gases were collected at the baseline and 5 min after oxygenation. The primary outcome was the arterial partial pressure of oxygen (PaO2). Secondary outcomes included hypoxia incidence (SpO2 < 95%), the difference in the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen concentration (ΔP/F ratio), the difference in the arterial partial pressure of carbon dioxide (ΔPaCO2), respiratory rate (RR) changes, and patient satisfaction. Results: After adjustment for the baseline PaO2, the HFNC group showed significantly higher intra-procedural PaO2 compared to the facemask group (299 ± 18.6 vs. 194 ± 19.0 mmHg, p < 0.001). No significant differences were found in the ΔP/F ratio, ΔPaCO2, or patient satisfaction. Among the secondary outcomes, RR was more stable in the HFNC group throughout the procedure (Group × Time interaction, p = 0.003). Conclusions: The HFNC significantly improved intra-procedural PaO2 during RFA under MAC but did not reduce hypoxia incidence or improve other clinical outcomes compared to facemask oxygenation. The stability of RR observed with the HFNC may reflect a physiological advantage, though further studies are needed to determine its clinical relevance. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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