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Search Results (196)

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Keywords = secondary traumatic stress

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36 pages, 876 KB  
Systematic Review
Therapeutic Potential of 2-(2-Benzofuranyl)-2-Imidazoline in Preclinical CNS Models: A Systematic Review of Mechanisms, Disease Models, and Cellular Targets
by In-Ae Choi, Ji Hee Yun, Jongmin Lee and Dong-Hee Choi
Pharmaceuticals 2026, 19(8), 1155; https://doi.org/10.3390/ph19081155 - 24 Jul 2026
Viewed by 242
Abstract
Background/Objectives: 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) is a selective imidazoline I2-site ligand that has shown neuroprotective and neuromodulatory effects in preclinical central nervous system (CNS) studies. However, the primary preclinical literature remains fragmented across disease models, outcome types, mechanistic endpoints, and cellular targets, making [...] Read more.
Background/Objectives: 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) is a selective imidazoline I2-site ligand that has shown neuroprotective and neuromodulatory effects in preclinical central nervous system (CNS) studies. However, the primary preclinical literature remains fragmented across disease models, outcome types, mechanistic endpoints, and cellular targets, making it difficult to define where its therapeutic-development potential is strongest and how disease- or model-specific functional effects relate to molecular, cellular, tissue, and blood–brain barrier/neurovascular unit (BBB/NVU)-related findings. Methods: This systematic review integrated preclinical evidence from 36 original studies identified in the PubMed, Web of Science, Embase, and Scopus databases through searches last updated on May 19, 2026, to evaluate the strength of evidence for 2-BFI across CNS-related models and to connect functional, molecular, cellular, and neurovascular findings. The evidence categories included ischemic stroke/neurovascular outcomes (n = 13), traumatic CNS injury (n = 2), neuroinflammatory/neurodegeneration-related models (n = 9), behavioral pharmacology (n = 8), and cellular mechanisms (n = 4). Eligible studies were original CNS-related animal, cellular, or behavioral/pharmacological studies that directly evaluated 2-BFI and reported neuroprotective, neurological, cellular, molecular, vascular, inflammatory, neurotransmitter-related, or behavioral outcomes. Findings were synthesized qualitatively, and risk of bias in in vivo animal studies was assessed using SYRCLE’s risk-of-bias tool. Results: The most extensive preclinical evidence was found in ischemic stroke and neurovascular injury models, in which 2-BFI attenuated infarct size, neurological deficits, and edema, and suppressed apoptosis-related injury and blood–brain barrier/neurovascular unit (BBB/NVU) disruption. Across models, these effects are best interpreted as modulation of interconnected secondary injury processes involving N-methyl-D-aspartate receptor (NMDAR)/Ca2+-dependent excitotoxicity, oxidative and mitochondrial stress, inflammatory amplification, regulated cell death, and neurovascular destabilization. Evidence from traumatic CNS injury, autoimmune neuroinflammation, Alzheimer’s disease-related models, chronic epilepsy, and cellular stress models broadened the CNS relevance of 2-BFI but remained less replicated or more mechanistically indirect than the stroke/neurovascular evidence. Behavioral and pharmacological studies additionally indicated that 2-BFI modulates neurotransmitter-related systems associated with pain-, affective-, addiction-, opioid-, and compulsivity-related outcomes, although these findings should be distinguished from disease-modifying neuroprotective evidence. Conclusions: Meta-analysis was not conducted because of heterogeneity in models, dosing regimens, treatment timing, and outcomes. Overall, the current evidence does not yet support definitive dosing, treatment timing, or clinical development recommendations for 2-BFI. The strongest preclinical therapeutic rationale is currently found in ischemic stroke and neurovascular injury settings, whereas other CNS indications require further validation. Future studies should define dose–response relationships, therapeutic windows, pharmacokinetic and safety profiles, sex- and age-related effects, and efficacy in clinically relevant comorbid models before clinical translation is considered. The review was not prospectively registered. Funding was provided by a National Research Foundation of Korea grant funded by the Korean government. Full article
(This article belongs to the Special Issue Advances in Neuropharmacology and Brain Injury Therapeutics)
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28 pages, 1130 KB  
Review
Psychotherapeutic Interventions and Psychosocial Outcomes Following Perinatal Loss: An Umbrella Review with a Patient-Centered Care Perspective
by Thalia Bellali, Anna Papadopoulou, Polyxeni Liamopoulou and Chrysovalantis Karagkounis
Healthcare 2026, 14(14), 2141; https://doi.org/10.3390/healthcare14142141 - 16 Jul 2026
Viewed by 533
Abstract
Background/Objectives: Perinatal loss is a profoundly distressing life event associated with grief, depression, anxiety, post-traumatic stress symptoms, and long-term psychosocial challenges among bereaved parents who experience miscarriage, stillbirth, or neonatal death. Although psychotherapeutic interventions are increasingly used to address these adverse outcomes, there [...] Read more.
Background/Objectives: Perinatal loss is a profoundly distressing life event associated with grief, depression, anxiety, post-traumatic stress symptoms, and long-term psychosocial challenges among bereaved parents who experience miscarriage, stillbirth, or neonatal death. Although psychotherapeutic interventions are increasingly used to address these adverse outcomes, there is limited synthesis on how characteristics consistent with a patient-centered care perspective are reflected in such interventions and how they may relate to psychosocial well-being. This umbrella review aimed to synthesize evidence on psychotherapeutic interventions following perinatal loss and to examine patient-centered care–related dimensions reported across the included reviews, including therapeutic communication, patient engagement, therapeutic relationships, emotional validation, and meaning-making processes. Methods: An umbrella review was conducted in accordance with the Joanna Briggs Institute methodological guidance. Systematic reviews and meta-analyses published between 2019 and 2025 were identified through searches of PubMed, CINAHL, PsycINFO, and the Cochrane Library from database inception to 31 May 2026. Eligible reviews examined psychotherapeutic, psychosocial, and psychological support interventions designed to improve grief, depression, anxiety, post-traumatic stress symptoms, psychological distress, coping, and psychosocial well-being among bereaved parents following perinatal loss. In accordance with the predefined secondary exploratory objective, a secondary interpretive synthesis examined patient-centered care–related dimensions described within the included reviews. Results: Five systematic reviews and meta-analyses met the inclusion criteria. Interventions included cognitive behavioral therapy, mindfulness-based approaches, bereavement counseling, psychosocial support programs, narrative interventions, supportive counseling, and digitally delivered psychological therapies. Across reviews, psychotherapeutic interventions were generally associated with beneficial effects on grief, depression, anxiety, post-traumatic stress symptoms, and broader indicators of psychosocial well-being. Communication-, support-, and engagement-related characteristics consistent with a patient-centered care perspective, including empathy, therapeutic alliance, individualized support, emotional validation, and continuity of communication, were identified through secondary interpretive synthesis as recurring features of beneficial interventions. Digital modalities, such as internet-based cognitive behavioral therapy and telephone-delivered counseling, were consistently described as supporting accessibility, engagement, and continuity of care. Conclusions: Psychotherapeutic interventions following perinatal loss appear to improve a range of psychosocial outcomes. A patient-centered care perspective may help interpret how communication, emotional validation, patient engagement, and supportive therapeutic relationships are described in relation to psychological adaptation after loss. These dimensions should be understood as interpretive characteristics identified across the included reviews rather than as directly measured mechanisms of intervention effectiveness. Future research should examine communication processes, therapeutic alliance, and patient engagement using validated measures, assess how these factors relate to intervention effectiveness, and support the development of integrated, patient-centered models of perinatal bereavement care. Full article
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23 pages, 1137 KB  
Article
Secondary Traumatic Stress and Positive Adaptation Among Social Workers: The Roles of Burnout, Compassion Satisfaction, and Perceived Social Support in a Cross-Sectional Study
by Fang Fu, Yumeng Zhu, Mandy Lau and Soon Noi Goh
Healthcare 2026, 14(14), 2060; https://doi.org/10.3390/healthcare14142060 - 9 Jul 2026
Viewed by 350
Abstract
Objectives: This study aimed to examine the associations of secondary traumatic stress with social workers’ positive psychological outcomes (resilience and post-traumatic growth) and to test the moderating roles of burnout, compassion satisfaction, and perceived social support. Methods: This study adopted a [...] Read more.
Objectives: This study aimed to examine the associations of secondary traumatic stress with social workers’ positive psychological outcomes (resilience and post-traumatic growth) and to test the moderating roles of burnout, compassion satisfaction, and perceived social support. Methods: This study adopted a cross-sectional survey design and recruited practicing social workers from health and social care institutions in Singapore and China. A total of 673 valid questionnaires were obtained, including 354 from Singapore and 319 from China. Hierarchical regression analysis was conducted to test the direct and moderating associations among the core variables. Results: Secondary traumatic stress was positively associated with post-traumatic growth (β = 0.25, p < 0.01) with no significant association with resilience. Burnout negatively moderated the secondary traumatic stress–post-traumatic growth link (β = −0.13, p < 0.01) but not the secondary traumatic stress–resilience relationship. Compassion satisfaction negatively moderated the associations of secondary traumatic stress with both resilience and post-traumatic growth (β = −0.14, −0.15, p < 0.01). Perceived social support showed no significant moderating roles but was positively associated with both adaptation indicators (β = 0.19, 0.14, p < 0.01). Conclusions: This study challenges the conventional “risk-protection” dichotomy by revealing a nuanced stress–adaptation mechanism. Secondary traumatic stress co-occurs with post-traumatic growth (PTG) rather than baseline resilience, while compassion satisfaction exhibits a paradoxical “buffering-ceiling” interaction that attenuates the positive associations between traumatic stress and growth. Practically, organizations must move beyond generic wellness programs to implement dual-track strategies: mitigating burnout to foster social workers’ growth potential while leveraging compassion satisfaction as an early-stage shield rather than a late-stage resilience enhancer. Full article
(This article belongs to the Special Issue Spirituality, Stress, and Well-Being of Healthcare Professionals)
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14 pages, 276 KB  
Article
Occupational Moral Injury and Professional Quality of Life Among a Group of Greek Nurses: A Cross-Sectional Study
by Evangelos C. Fradelos, Anna Patsopoulou, Maria Robie, Eirini Stylianou, Aikaterini Toska, Pavlos Sarafis, Ioanna V. Papathanasiou, Anna Mauroforou and Maria Saridi
Healthcare 2026, 14(13), 1969; https://doi.org/10.3390/healthcare14131969 - 2 Jul 2026
Viewed by 360
Abstract
Background: Occupational moral injury is associated with nurses’ psychological well-being, yet evidence linking it to professional quality of life remains limited, and no validated Greek version of the Occupational Moral Injury Scale (OMIS) has been available. Methods: A cross-sectional study was [...] Read more.
Background: Occupational moral injury is associated with nurses’ psychological well-being, yet evidence linking it to professional quality of life remains limited, and no validated Greek version of the Occupational Moral Injury Scale (OMIS) has been available. Methods: A cross-sectional study was conducted among 301 nurses from two public hospitals in Greece. Using convenience sampling, 350 questionnaires were distributed, yielding an 86.0% response rate. Participants completed the Occupational Moral Injury Scale (OMIS) and the Professional Quality of Life Scale Version 5 (ProQOL-V). The OMIS was translated and culturally adapted into Greek through a forward–backward translation process, and its validity and reliability were assessed using confirmatory factor analysis and internal consistency testing. Results: The Greek OMIS demonstrated excellent internal consistency (Cronbach’s α = 0.95). CFA provided preliminary support for the proposed factorial structure, although model fit indices indicated a marginal-to-moderate fit (CFI = 0.887, TLI = 0.866, SRMR = 0.070 and GFI 0.902). Participants reported relatively high compassion satisfaction (M = 37.30, SD = 7.35) and moderate levels of burnout (M = 23.36, SD = 5.06) and secondary traumatic stress (M = 22.13, SD = 7.28). Betrayal was negatively associated with compassion satisfaction (r = −0.151, p = 0.009) and positively associated with burnout (r = 0.427, p < 0.001) and secondary traumatic stress (r = 0.366, p < 0.001). Regression analyses showed that dimensions of moral injury were associated with burnout, secondary traumatic stress, and compassion satisfaction, with betrayal showing the strongest associations. Conclusions: Occupational moral injury was associated with poorer professional quality of life, underscoring the need for organizational support, ethical resources, and clinical supervision to promote healthcare professionals’ well-being and resilience. Full article
(This article belongs to the Special Issue Well-Being of Healthcare Professionals: New Insights After COVID-19)
11 pages, 8793 KB  
Article
The Importance of Instrumentation Length in Ankylosing Spinal Disorders and Thoracolumbar Fractures
by Federico Fusini, Alessandro Rava, Giosuè Gargiulo, Domenico Messina, Alberto Lorenzi, Silvia Amico, Gabriele Colò and Massimo Girardo
J. Clin. Med. 2026, 15(13), 5082; https://doi.org/10.3390/jcm15135082 - 30 Jun 2026
Viewed by 331
Abstract
Background/Objectives: Ankylosing Spinal Disorders (ASDs) encompass a heterogeneous group of rheumatic diseases characterized by progressive ankylosis of the axial skeleton, including Ankylosing Spondylitis (AS), Diffuse Idiopathic Skeletal Hyperostosis (DISH), and Non-Radiographic Axial Spondyloarthritis (nr-AxSpA). Spinal ankylosis profoundly alters the biomechanical properties of [...] Read more.
Background/Objectives: Ankylosing Spinal Disorders (ASDs) encompass a heterogeneous group of rheumatic diseases characterized by progressive ankylosis of the axial skeleton, including Ankylosing Spondylitis (AS), Diffuse Idiopathic Skeletal Hyperostosis (DISH), and Non-Radiographic Axial Spondyloarthritis (nr-AxSpA). Spinal ankylosis profoundly alters the biomechanical properties of the vertebral column, transforming it into a rigid long-bone equivalent and dramatically increasing fracture risk even after low-energy trauma. Once a fracture occurs, the long lever arm created by the ankylosed segments generates enormous mechanical stress at the fracture site, making surgical stabilization mandatory in the vast majority of cases. Long posterior instrumentation is the treatment of choice; however, no consensus exists regarding the optimal number of instrumented levels. The aim of this study is to clinically and radiologically evaluate long posterior instrumentation in the 3 + 3 (3 proximal and 3 caudal screws), 3 + 2 (3 proximal and 2 caudal screws), or 2 + 2 (2 proximal and 2 caudal screws) configuration for the treatment of traumatic ASD thoracolumbar vertebral fractures, in terms of implant failure, infection rate, and mortality. Methods: Between 2018 and 2023, 65 consecutive patients with ASD-related thoracolumbar vertebral fractures were treated at our institution. After applying pre-defined inclusion and exclusion criteria, 37 patients were enrolled. Patients were retrospectively divided into three groups according to the posterior arthrodesis configuration (notation indicates number of instrumented vertebral levels proximal + distal to the fracture: 3 + 3, 3 + 2, or 2 + 2). Radiological outcomes were assessed for loosening, screw cut-out, and implant breakage. Infection and mortality rates within 3 months from surgery were evaluated as secondary endpoints. Statistical analysis was performed using the Fisher exact test (significance set at p < 0.05). Results: Thirty-seven patients (28 males and 9 females; mean age 77 ± 7.3 years) were included, with a mean follow-up of 30 ± 5.3 months. Instrumentation configurations were as follows: 23 (3 + 3), 5 (3 + 2), and 9 (2 + 2). Three implant failures (8.1%) and four infections (10.8%) were recorded. Eleven patients died within 3 months of surgery. A statistically significant difference was found between instrumentation length and mechanical complications (p = 0.0468), while no significant difference was observed for infection (p = 1) or mortality rate (p = 0.137). Conclusions: In this exploratory retrospective cohort, the 3 + 3 configuration was associated with the lowest observed rate of implant failure in ASD thoracolumbar fractures, suggesting a potential mechanical advantage over shorter constructs that warrants confirmation in larger prospective studies. No significant correlation was found between instrumentation length and infection rate or early mortality. Prospective, multicentre studies with larger cohorts are warranted to establish definitive guidelines for instrumentation length in this challenging patient population. Full article
(This article belongs to the Special Issue Clinical Advancements in Orthopedic Trauma Treatments)
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15 pages, 513 KB  
Article
When Self-Care Isn’t Enough: The Practice of Soul Care and Mitigation of Soul Wounds in Public Child Welfare Workers
by Nancy Kuhuski and Sarah Dubitzky
Soc. Sci. 2026, 15(6), 409; https://doi.org/10.3390/socsci15060409 - 22 Jun 2026
Viewed by 305
Abstract
Protecting the safety and well-being of children in public child welfare is one of the most critical and demanding jobs in social work. Burnout, secondary traumatic stress, and moral injury are prevalent in this field and often occur simultaneously. This intersectional experience impacts [...] Read more.
Protecting the safety and well-being of children in public child welfare is one of the most critical and demanding jobs in social work. Burnout, secondary traumatic stress, and moral injury are prevalent in this field and often occur simultaneously. This intersectional experience impacts the deepest level of a person—their soul. When left unaddressed, these soul wounds come at a high cost to the workers, organizations they work for, the clients they serve, and their greater communities. This qualitative study sought to explore and identify the characteristics of soul care and the power it has to transform the lived experiences of child welfare workers. Collaborative, semi-structured interviews were conducted with seven workers who had been in this field for 10 or more years and described themselves as having good soul care. Findings from this study concluded the combination of strongly held core beliefs and engagement in a steady regulation loop constituted soul care. Soul care can occur regardless of circumstance. When a soul wound occurs, the Soul Wound Cycle is activated. The momentum of the regulation loop propels one’s movement through this cycle, allowing the processing of the soul wound, resulting in increased resiliency and regaining of equilibrium, ultimately leading to better outcomes for children. Full article
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13 pages, 862 KB  
Article
Temporal Increase in Strict Spontaneous Intracerebral Hemorrhage Admissions During the First March Following Direct Israel–Iran Hostilities: Preliminary Single-Center Findings from a Decade-Referenced Neuroscience Services Cohort
by Paz Kelmer, Shachar Zion Shemesh, Jose Asprilla, Omri Cohen, Zvi R. Cohen and Lior Ungar
Int. J. Environ. Res. Public Health 2026, 23(6), 772; https://doi.org/10.3390/ijerph23060772 - 8 Jun 2026
Viewed by 598
Abstract
Objective: On 28 February 2026, Israel entered direct large-scale hostilities with Iran under Operation Roaring Lion. The opening phase was characterized by repeated missile alerts, civilian protected-space instructions, and rapid reorganization of hospital activity into protected areas. We observed an apparent increase [...] Read more.
Objective: On 28 February 2026, Israel entered direct large-scale hostilities with Iran under Operation Roaring Lion. The opening phase was characterized by repeated missile alerts, civilian protected-space instructions, and rapid reorganization of hospital activity into protected areas. We observed an apparent increase in strict spontaneous intracerebral hemorrhage admissions during March 2026 within our linked neurology/neurosurgery services dataset. The aim of this preliminary single-center study was to determine whether March 2026 was temporally associated with a higher proportional burden of strict spontaneous intracerebral hemorrhage admissions compared with March cohorts from the preceding decade and whether this pattern was also observed for acute ischemic stroke or non-traumatic subarachnoid hemorrhage. Methods: We performed a retrospective observational cohort study of all unique March admissions captured within a linked neurology/neurosurgery services dataset from 2016 through 2026. Hospitalizations were deduplicated by admission number. March 2026 was treated as the first full March occurring after the onset of direct Israel–Iran hostilities on 28 February 2026. Strict spontaneous ICH was defined using diagnosis-text phenotyping that included intraparenchymal or intracerebral hemorrhage terminology while excluding trauma, subarachnoid hemorrhage, subdural hematoma, aneurysm, arteriovenous malformation, tumor-related hemorrhage, cavernoma, venous sinus thrombosis, dissection, and other clearly secondary etiologies. Comparator phenotypes included acute ischemic stroke and non-traumatic subarachnoid hemorrhage (SAH). Results: Across 3855 unique March admissions, 68 met criteria for strict spontaneous ICH. In March 2026, 9 of 223 admissions (4.0%) were classified as strict spontaneous ICH, compared with 59 of 3632 admissions (1.6%) across March 2016–2025, yielding a rate ratio of 2.48 (95% CI 1.25–4.94; p = 0.015). Patients with strict spontaneous ICH in March 2026 were older (mean age 72.3 vs. 65.8 years), and 7 of 9 cases (77.8%) occurred in patients aged ≥70 years compared with 25 of 59 (42.4%) historically (p = 0.073). Acute ischemic stroke did not increase in March 2026 (7.6% vs. 9.4%; p = 0.475), and non-traumatic SAH showed only a non-significant numerical increase (2.7% vs. 1.4%; p = 0.147). Sensitivity analyses showed a directionally consistent but statistically non-significant increase when March 2026 was compared with March 2025 alone (4.0% vs. 1.2%; rate ratio 3.36, 95% CI 0.92–12.27; p = 0.076) and with a rolling 3-year March baseline from 2023 through 2025 (4.0% vs. 2.1%; rate ratio 1.93, 95% CI 0.88–4.23; p = 0.143). In-hospital mortality among strict spontaneous ICH patients was 1 of 9 (11.1%) in March 2026 versus 4 of 59 (6.8%) in March 2016–2025. Conclusions: In this preliminary single-center neurology/neurosurgery services cohort, March 2026 showed a higher proportional burden of strict spontaneous intracerebral hemorrhage admissions than March cohorts from the preceding decade, while acute ischemic stroke did not increase. Sensitivity analyses using March 2025 alone and a rolling 3-year March baseline were directionally consistent but did not reach statistical significance. These findings should therefore be interpreted as a hypothesis-generating temporal association rather than evidence of causality or population-level incidence. Wartime-related psychological stress, sleep disruption, altered healthcare access, blood pressure dysregulation, and medication nonadherence are biologically plausible contributors, but individual-level blood pressure, medication exposure, body mass index, time-to-admission, direct stress exposure, and detailed outcome data were not available in the present dataset. Multicenter, hospital-wide, and registry-based validation with seasonal and systems-level sensitivity analyses is required. Full article
(This article belongs to the Section Environmental Health)
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30 pages, 34811 KB  
Article
Repurposing Leucovorin for Mild Traumatic Brain Injury: Evidence from Biochemical and Behavioral Outcomes in Rats
by Erdem Arslan and Melike Ordu
Pharmaceuticals 2026, 19(6), 865; https://doi.org/10.3390/ph19060865 - 30 May 2026
Viewed by 582
Abstract
Background/Objectives: Mild traumatic brain injury (mTBI) is common and may result in persistent cognitive and affective disturbances driven, at least in part, by delayed secondary injury mechanisms, including oxidative stress, neuroinflammation, apoptosis-related signaling, and impaired neuroplasticity. Pharmacological strategies targeting these interconnected processes remain [...] Read more.
Background/Objectives: Mild traumatic brain injury (mTBI) is common and may result in persistent cognitive and affective disturbances driven, at least in part, by delayed secondary injury mechanisms, including oxidative stress, neuroinflammation, apoptosis-related signaling, and impaired neuroplasticity. Pharmacological strategies targeting these interconnected processes remain limited. The present study investigated leucovorin, also known as folinic acid, a clinically approved reduced folate, as a potential repurposing candidate in an experimental model of mTBI. Methods: Male Wistar rats were subjected to mild diffuse brain injury using a modified weight-drop model and received a single intraperitoneal dose of leucovorin (20 mg/kg). Behavioral performance was evaluated using the open field, elevated plus maze, forced swim, and novel object recognition tests. Oxidative stress markers, including total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), as well as inflammatory mediators tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), caspase-3, brain-derived neurotrophic factor (BDNF), and acetylcholinesterase (AChE), were measured in hippocampal tissue and plasma. Histopathological and immunohistochemical evaluations were also performed in cortical and hippocampal regions. Results: Experimental mTBI was associated with anxiety-like and depressive-like behaviors and impaired recognition memory, whereas basal locomotor activity was not significantly altered. Trauma was also associated with increased oxidative stress, elevated inflammatory and apoptosis-related markers, reduced BDNF levels, altered AChE activity, and histopathological abnormalities. Compared with untreated mTBI animals, leucovorin-treated animals showed attenuation of biochemical and tissue alterations, accompanied by improved behavioral outcomes. Immunohistochemical findings were consistent with reduced inflammatory labeling and relative preservation of tissue architecture following leucovorin treatment. Conclusions: Leucovorin attenuated behavioral, biochemical, histopathological, and immunohistochemical alterations associated with experimental mTBI. These findings suggest that leucovorin may have neuroprotective potential in this setting; however, further studies are needed to clarify the underlying mechanisms, optimal treatment paradigms, and translational relevance. Full article
(This article belongs to the Section Pharmacology)
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37 pages, 8260 KB  
Review
Primary Blast-Induced Traumatic Brain Injury as a Risk Factor for (Cerebro)vascular Disorder: Clinical Manifestations, Blast Physics, Biomechanics, Pathobiology, and Critical Gaps
by Denes V. Agoston and James S. Meabon
Int. J. Mol. Sci. 2026, 27(11), 4669; https://doi.org/10.3390/ijms27114669 - 22 May 2026
Viewed by 1649
Abstract
Exposure to blast waves without kinetic, penetrating, thermal, or toxic components causes a distinct form of traumatic brain injury, termed primary blast-induced TBI (pbTBI). Clinical manifestations of pbTBI span a wide spectrum, ranging from life-threatening intracranial hemorrhage, hyperemia, and delayed cerebral edema to [...] Read more.
Exposure to blast waves without kinetic, penetrating, thermal, or toxic components causes a distinct form of traumatic brain injury, termed primary blast-induced TBI (pbTBI). Clinical manifestations of pbTBI span a wide spectrum, ranging from life-threatening intracranial hemorrhage, hyperemia, and delayed cerebral edema to mild and transient neurological symptoms without detectable structural abnormalities on routine imaging. At the mild end of the spectrum, symptoms after a single exposure may resolve quickly, yet repeated exposures—even at very low levels, termed “subconcussive”—can develop into post-concussive syndrome (PCS) or persistent post-concussive symptoms (PPCS) in a subset of individuals. Despite extensive studies, the molecular pathobiology linking primary blast exposure to delayed and sometimes chronic neurobehavioral deficits remains incompletely understood. A mechanistic framework connecting blast-wave physics to biomechanics to biological vulnerability may therefore help define exposure hazards, interpret clinical symptomatology, and guide diagnostic and therapeutic development. This review summarizes the physics of primary blast waves, the resulting biomechanical responses, and candidate biological substrates, emphasizing structures and interfaces with distinct acoustic impedances across anatomical, tissue, cellular, and molecular scales. We synthesize evidence supporting the hypothesis that the cerebral vasculature and endothelial cells represent critically vulnerable substrates of primary blast-wave injury, in part because the vascular tree constitutes the brain’s largest and most widely distributed interface between compartments with different acoustic impedances. Across experimental and human studies, endothelial stress, vascular injury, and downstream neuroinflammation emerge as convergent molecular responses to primary blast exposure. Temporal dynamics are central to understanding pbTBI because many blast-induced processes unfold in sequential phases. These observations support conceptualizing pbTBI as a condition characterized by prominent cerebrovascular injury of varying severity with secondary consequences for neuronal signaling, network function, and behavior. Within this framework, cerebrovascular and neurovascular unit (NVU) dysfunction provides a parsimonious bridge between primary blast-wave exposure and chronic symptom trajectories, where vascular pathology may offer more accessible therapeutic targets than neuronal injury. Key knowledge gaps include identifying which physical component(s) of the blast are most injurious, establishing biologically meaningful dose–response relationships at molecular and physiological levels, and defining windows of vulnerability during recovery that are relevant to repeated exposures. Addressing these gaps is essential for refining safety protocols, improving diagnostic specificity through mechanism-informed biomarkers, and developing evidence-based molecular and vascular therapeutic targets for pbTBI-associated conditions. Progress will require integrating waveform-aware dosimetry with longitudinal physiological and molecular monitoring across both preclinical and human cohorts. Such integration offers a practical path toward translating blast physics into actionable medical guidance for prevention, triage, and recovery management. Full article
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13 pages, 961 KB  
Review
Spinal Cord Ischemia Following Thoracoabdominal Aortic Aneurysm Repair: Translational Insights from Stroke and Traumatic Injury for Biomarker Development
by James A. Kelly, Miranda Witheford, Kong Teng Tan, Tiam Feridooni, Daniyal Mahmood, Carmen Garcia-Mere and Thomas F. Lindsay
Biomedicines 2026, 14(5), 1144; https://doi.org/10.3390/biomedicines14051144 - 18 May 2026
Viewed by 600
Abstract
Background: Spinal cord ischemia (SCI) is a severe complication of thoracoabdominal aortic aneurysm (TAAA) repair, associated with substantial morbidity and mortality. Despite advances in operative techniques, its pathophysiology remains incompletely understood, with no reliable biomarkers available for early detection or risk stratification. Methods: [...] Read more.
Background: Spinal cord ischemia (SCI) is a severe complication of thoracoabdominal aortic aneurysm (TAAA) repair, associated with substantial morbidity and mortality. Despite advances in operative techniques, its pathophysiology remains incompletely understood, with no reliable biomarkers available for early detection or risk stratification. Methods: This narrative review synthesizes current evidence on the pathophysiology of SCI following aortic intervention, integrating insights from ischemic stroke and traumatic spinal cord injury to identify key mechanistic pathways and potential biomarker targets. Results: SCI results from multifactorial impairment of spinal cord perfusion pressure (SCPP) driven by extensive aortic coverage, disruption of segmental arterial inflow, hypotension, and impaired collateral circulation. While acute hypoperfusion initiates injury, secondary processes—including excitotoxicity, oxidative stress, and neuroinflammation—drive progression. Cytokine signaling and immune activation contribute to blood–spinal cord barrier disruption and vasogenic edema, with Aquaporin-4 playing a central role in delayed injury. Candidate biomarkers, including neuron-specific enolase, S100β, and glial fibrillary acidic protein, reflect neuronal damage but lack sufficient sensitivity and temporal resolution for clinical use. Emerging evidence supports a multimodal biomarker approach incorporating inflammatory, structural, and Aquaporin-4-dependent edema-related pathways. Conclusions: Spinal cord ischemia following thoracoabdominal aortic aneurysm repair is a dynamic and multifactorial process in which reduced spinal cord perfusion pressure represents a final common pathway linking diverse perioperative factors to ischemic injury. Secondary mechanisms, particularly neuroinflammation and Aquaporin-4-driven vasogenic edema, play a central role in injury propagation and represent promising targets for biomarker development. Future strategies should focus on longitudinal, multimodal biomarker approaches to improve early detection, risk stratification, and therapeutic intervention. Full article
(This article belongs to the Special Issue Aortic Aneurysm: Mechanisms, Biomarkers, and Therapeutic Strategy)
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19 pages, 6582 KB  
Article
Extracellular Vesicle and Plasma miRNAs as Candidate Biomarkers of Traumatic Brain Injury in the Context of Polytrauma
by Cora Rebecca Schindler, Dirk Henrich, Lena Krämer, Inna Schaible, Jason-Alexander Hörauf, Aileen Ritter, Philipp Störmann, Rald Victor Maria Groven, Markus Huber-Lang, Ingo Marzi and Liudmila Leppik
Int. J. Mol. Sci. 2026, 27(10), 4248; https://doi.org/10.3390/ijms27104248 - 10 May 2026
Viewed by 777
Abstract
Severe traumatic brain injury (TBI) is a leading cause of mortality and long-term disability in polytrauma (PT) patients, and its clinical outcome remains difficult to predict due to clinical heterogeneity and secondary injury mechanisms. Current diagnostic and prognostic approaches based on clinical assessment [...] Read more.
Severe traumatic brain injury (TBI) is a leading cause of mortality and long-term disability in polytrauma (PT) patients, and its clinical outcome remains difficult to predict due to clinical heterogeneity and secondary injury mechanisms. Current diagnostic and prognostic approaches based on clinical assessment and imaging are limited, particularly in PT where neurological evaluation is often impaired. This study aimed to compare plasma- and extracellular vesicle (EV)-associated microRNA (miRNA) signatures in patients with severe TBI and healthy controls to identify their potential as minimally invasive biomarkers and to improve understanding of molecular responses. For profiling circulating miRNAs, blood samples were collected at ≤3 h and at 48 h after admission. In the screening phase, plasma samples of n = 15 patients with severe isolated TBI (Abbreviated Injury Scale [AIS]Head ≥ 4, all other AIS ≤ 1) and n = 15 age- and sex-matched healthy controls were pooled (n = 5/pool) and subjected to next-generation sequencing (NGS). In the following validation phase, n = 25 severely injured trauma patients (Injury Severity Score [ISS] ≥ 16) were enrolled and stratified into PT without TBI (PT; AISHead = 0; n = 13) and isolated TBI (n = 12). Differentially expressed candidate miRNAs identified in the screening phase were validated in individual plasma and EV samples using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). Functional enrichment and pathway analyses were performed using miRNet. NGS identified more differentially expressed miRNAs in plasma (ER: 103; 48 h: 65) than in EVs (Emergency Room [ER]: 14; 48 h: 32). Functional enrichment analysis indicated associations with pathways related to cellular stress, senescence, growth factor signaling, transcriptional regulation, and apoptosis. In validation, 12 of 16 plasma and 10 of 15 EV-miRNAs were confirmed as differentially expressed in TBI patients; among these, three plasma and four EV miRNAs differed between TBI and PT. After adjustment, most plasma miRNAs were associated with injury severity rather than group status. EV miRNA profiles showed heterogeneous patterns, with miR-1469 associated with TBI group status in adjusted analysis, while miR-1237-5p was linked to injury severity and other EV miRNAs showed no consistent group-specific effects. Plasma miRNAs mainly correlated with systemic injury markers, whereas EV miR-1469 showed a moderate association with the Glasgow Coma Scale (GCS). Overall, circulating miRNA profiles after injury appear to be predominantly influenced by systemic trauma severity rather than TBI-specific effects. Plasma miRNAs mainly reflected general injury burden, whereas EV-associated miRNAs showed more heterogeneous patterns, with miR-1469 emerging as a candidate associated with TBI after adjustment for clinical covariates. These findings suggest that EV-derived miRNAs, particularly miR-1469, may provide more targeted signals related to brain injury and warrant further investigation. Full article
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17 pages, 3331 KB  
Article
Service Dog Training Interventions for Veterans with Post-Traumatic Stress: Examining Gender-Based Differences in Psychosocial Outcomes
by Shahar Almog, Cheryl A. Krause-Parello, Alejandra Quintero, Deborah Taber and Erika Friedmann
Healthcare 2026, 14(9), 1253; https://doi.org/10.3390/healthcare14091253 - 6 May 2026
Viewed by 707
Abstract
Background: Poor mental health is prevalent among veterans who suffer from post-traumatic stress disorder (PTSD) and other psychiatric conditions. Canine-assisted interventions may improve psychological and social health in veterans. The parent study, a randomized controlled trial, revealed improvements in PTSD following both a [...] Read more.
Background: Poor mental health is prevalent among veterans who suffer from post-traumatic stress disorder (PTSD) and other psychiatric conditions. Canine-assisted interventions may improve psychological and social health in veterans. The parent study, a randomized controlled trial, revealed improvements in PTSD following both a service dog training program and an active control condition consisting of virtual dog training lessons. Thus, in the present post hoc secondary analysis, we analyzed both groups together (pooled arms) to examine gender-based differences in the effects of the altruistic service dog training programs on psychosocial outcomes. Methods: Veterans (N = 59) participated either in hands-on (with a dog and trainer) or virtual (no dog present) dog training programs over eight weeks and completed self-reported psychosocial measures before and after the program. Mixed-effect linear models were used to assess the interaction between time and gender on a series of psychosocial outcomes in the pooled sample. Results: The findings supported greater psychosocial improvements for female participants compared to male participants, including significant improvements in PTSD, perceived stress, and perceived physical health, and feeling greater closeness and lower avoidance in close relationships (ps < 0.05). The results revealed moderate to large effect sizes among female participants, suggesting meaningful clinical effects of the interventions (ds = 0.47–0.70). Conclusions: While the secondary analysis and small sample size limit causal inferences, the exploratory evidence suggests greater improvements in psychosocial health in female veterans after participating in the service dog training programs. Future research should tailor interventions to optimize the therapeutic effects for male and female veterans and identify other individual characteristics involved, such as combat exposure or post-traumatic stress symptom severity. Full article
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31 pages, 3152 KB  
Article
Psychosocial Impact of COVID-19 on Intensive Care Unit Personnel: A Repeated Cross-Sectional Survey Assessment Before, During, and After the First Peak
by Nicholas C. Watson, Kathrine Kelly, Laura Krech, Alistair Chapman, Steffen Pounders, Matthew Armstrong, Charles J. Gibson and Gaby Iskander
Healthcare 2026, 14(9), 1154; https://doi.org/10.3390/healthcare14091154 - 25 Apr 2026
Viewed by 588
Abstract
Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic presented significant psychosocial challenges to intensive care unit health care workers (ICU HCW). Prior studies typically used single cross-sectional samples to focus on elements of burnout and psychological stress. We sought to serially assess quality [...] Read more.
Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic presented significant psychosocial challenges to intensive care unit health care workers (ICU HCW). Prior studies typically used single cross-sectional samples to focus on elements of burnout and psychological stress. We sought to serially assess quality of life and willingness to work before, during, and after the first peak of COVID-19. Methods: Two survey instruments were prospectively administered at regular intervals to multidisciplinary ICU HCWs, initiating at the local onset of COVID-19 and ending 6 months after the first peak ICU census of COVID-19 patients. Results: ICU HCWs reported high levels of compassion satisfaction, burnout, and secondary traumatic stress before, during and after the first peak of COVID-19. Motivation to work declined, and hesitation to work increased from study initiation to the peak ICU census of COVID-19 patients. Hesitation to work was greater in female HCWs and cardiothoracic ICU HCWs. Motivation to work was higher in those working in operating rooms compared to those in the ICU. Concerns about becoming infected, feelings of isolation, and exhaustion were associated with high hesitation to work. Feeling protected by the government and hospital was associated with decreased hesitation and increased motivation to work. Conclusions: ICU HCWs experienced high levels of stress throughout the first year of COVID-19, while satisfaction with work remained high. Willingness to work was associated with gender, work location, ICU subtype, concerns about infection risk, feelings of exhaustion, and feelings of institutional protection. Because the study methodology precludes causal inference and low survey response rates indicate that findings should be interpreted with caution, these results are best viewed as hypothesis-generating for future work aimed at improving stress mitigation in ICU HCWs. Full article
(This article belongs to the Collection The Impact of COVID-19 on Healthcare Services)
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22 pages, 9719 KB  
Article
A Pilot Randomized Controlled Trial of a Mindful Attention Training Workshop for Firefighters
by Antoine Lebeaut, Maya Zegel, Samuel J. Buser and Anka A. Vujanovic
Occup. Health 2026, 1(2), 17; https://doi.org/10.3390/occuphealth1020017 - 23 Apr 2026
Cited by 1 | Viewed by 790
Abstract
Firefighters are regularly exposed to occupational stress and potentially traumatic events. However, few evidence-based, fire service-specific interventions exist. Brief, mindfulness-based interventions may help address these challenges by improving regulation skills and reducing psychological distress. This pilot randomized controlled trial primarily evaluated the feasibility [...] Read more.
Firefighters are regularly exposed to occupational stress and potentially traumatic events. However, few evidence-based, fire service-specific interventions exist. Brief, mindfulness-based interventions may help address these challenges by improving regulation skills and reducing psychological distress. This pilot randomized controlled trial primarily evaluated the feasibility and acceptability of a one-session, group-based, virtual mindful attention training workshop developed specifically for firefighters, with secondary evaluation of preliminary efficacy. Firefighters (N = 82) were recruited from multiple fire departments across a large U.S. Southwestern metropolitan area and randomized to the mindful attention workshop (n = 45) or a waitlist control condition (n = 37). Feasibility outcomes were mixed, with strong enrollment among eligible participants (74.5%) but relatively low workshop attendance among those randomized to the intervention (53.3%). A total of 24 firefighters completed the workshop and found it to be helpful, informative, and relevant to the challenges faced in the fire service, with group processes characterized by high comfort, understanding, and low conflict. However, no significant between-group differences were observed in reductions in symptom severity or increases in mindfulness-based outcomes. Post hoc descriptive analyses revealed that most firefighters expressed strong interest in digitally delivered mental health content and the vast majority perceived online or app-based firefighter-specific mental health resources as helpful. Findings indicate mixed feasibility, strong acceptability among attendees, and a lack of preliminary efficacy, and highlight directions for refining intervention delivery of this pilot workshop and evaluating clinical impact in future trials. Full article
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15 pages, 336 KB  
Article
The Mediating Role of Burnout and Secondary Traumatic Stress in the Relationship Between Perceived Stress and Quality of Life Among Nurses
by Marin Mamić, Tihomir Jovanović, Božica Lovrić, Gabriela Katharina Pomper, Ivana Mamić, Ivana Barać, Robert Lovrić, Goranka Rafaj, Danijela Kumpović and Ivan Vukoja
Int. J. Environ. Res. Public Health 2026, 23(4), 540; https://doi.org/10.3390/ijerph23040540 - 21 Apr 2026
Viewed by 971
Abstract
(1) Background: Nurses are exposed to occupational stressors that may impair their well-being and quality of life. This study examined whether burnout and secondary traumatic stress mediate the relationship between perceived stress and physical and psychological quality of life. (2) Methods: A cross-sectional [...] Read more.
(1) Background: Nurses are exposed to occupational stressors that may impair their well-being and quality of life. This study examined whether burnout and secondary traumatic stress mediate the relationship between perceived stress and physical and psychological quality of life. (2) Methods: A cross-sectional study included 294 nurses employed at the Clinical Hospital Center Osijek, Croatia. Data were collected using the Perceived Stress Scale (PSS-10), the Burnout and Secondary Traumatic Stress subscales of the Professional Quality of Life Scale (ProQOL-5), and the physical and psychological domains of the WHOQOL-BREF. Pearson correlations and path analysis were used. (3) Results: Perceived stress showed significant negative effects on physical (β = −0.291; p < 0.001) and psychological quality of life (β = −0.217; p < 0.001), and positive effects on burnout (β = 0.230; p < 0.001) and secondary traumatic stress (β = 0.171; p = 0.002). Burnout significantly mediated both relationships, while secondary traumatic stress did not. The model explained 20.8% and 19.3% of variance in physical and psychological quality of life. (4) Conclusions: Burnout represents an important pathway linking perceived stress with poorer quality of life among nurses. Full article
(This article belongs to the Special Issue Exploring Quality of Life in Nursing and Patient Care)
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