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Search Results (585)

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Keywords = course of recovery

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12 pages, 724 KB  
Case Report
Fulminant Multidrug-Resistant Streptococcus pneumoniae Meningoencephalitis After Elective ENT Surgery: A Case Report
by Corina-Ioana Anton, Madalina Maria Zamfir, Alexandru Ghiță and Mihaela Raluca Mititelu
Microorganisms 2025, 13(10), 2315; https://doi.org/10.3390/microorganisms13102315 - 7 Oct 2025
Abstract
Pneumococcal meningoencephalitis is a severe infection associated with high morbidity and mortality. Although typically community-acquired, postoperative cases following elective ENT surgery are exceedingly rare. Antimicrobial resistance (AMR) among Streptococcus pneumoniae further complicates management, and missed opportunities for vaccination represent preventable risks. We report [...] Read more.
Pneumococcal meningoencephalitis is a severe infection associated with high morbidity and mortality. Although typically community-acquired, postoperative cases following elective ENT surgery are exceedingly rare. Antimicrobial resistance (AMR) among Streptococcus pneumoniae further complicates management, and missed opportunities for vaccination represent preventable risks. We report a case of a 41-year-old man with multiple comorbidities who developed fulminant S. pneumoniae meningitis 48 h after septoturbinoplasty. The clinical course was atypical, with altered consciousness but no classical meningeal signs, necessitating urgent intubation and intensive care admission. Cerebrospinal fluid cultures identified an MDR pneumococcal strain resistant to penicillin and macrolides but susceptible to vancomycin and meropenem. Empirical therapy with vancomycin and meropenem, combined with adjunctive corticosteroids and multidisciplinary ICU care, led to complete neurological recovery. This case highlights a rare but life-threatening postoperative complication and underscores two critical lessons. First, the growing challenge of multidrug-resistant pneumococcus requires timely recognition, aggressive empiric therapy, and access to effective agents. Second, the absence of pneumococcal vaccination in this high-risk surgical patient illustrates a preventable gap in care. Integrating vaccination screening into preoperative evaluations may reduce the risk of catastrophic postoperative CNS infections. Full article
(This article belongs to the Section Medical Microbiology)
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15 pages, 1250 KB  
Article
Kinetics of Serum Myoglobin and Creatine Kinase Related to Exercise-Induced Muscle Damage and ACTN3 Polymorphism in Military Paratroopers Under Intense Exercise
by Rachel de S. Augusto, Adrieli Dill, Eliezer Souza, Tatiana L. S. Nogueira, Diego V. Gomes, Jorge Paiva, Marcos Dornelas-Ribeiro and Caleb G. M. Santos
J. Funct. Morphol. Kinesiol. 2025, 10(4), 381; https://doi.org/10.3390/jfmk10040381 - 2 Oct 2025
Abstract
Background: Physical conditioning is essential to meet the operational demands of military environments. However, high-intensity exercise provokes muscle microinjuries resulting in exercise-induced muscle damage. This condition is typically monitored using serum biomarkers such as creatine kinase (CK), myoglobin (MYO), and lactate dehydrogenase [...] Read more.
Background: Physical conditioning is essential to meet the operational demands of military environments. However, high-intensity exercise provokes muscle microinjuries resulting in exercise-induced muscle damage. This condition is typically monitored using serum biomarkers such as creatine kinase (CK), myoglobin (MYO), and lactate dehydrogenase (LDH). Nevertheless, individual variability and genetic factors complicate the interpretation. In this context, the rs1815739 variant (ACTN3), the most common variant related to exercise phenotypes, hypothetically could interfere with the muscle physiological response. This study aimed to evaluate the kinetics of serum biomarkers during a high-intensity activity and their potential association with rs1815739 polymorphism. Materials and Methods: 32 male cadets were selected during the Army Paratrooper Course. Serum was obtained at six distinct moments while they performed regular course tests and recovery time. Borg scale was assessed in 2 moments (~11 and ~17). Results: Serum levels of CK, CK-MB, MYO, and LDH significantly increase after exercise, proportionally to Borg’s level, following the applicability of longitudinal studies to understand biomarker levels in response to exercise. R allele carriers (ACTN3) were only slightly associated with greater levels of MYO and CK, mainly in relative kinetic levels, and especially at moments of greater physical demand/recovery. Although the ACTN3 was slightly related to different biomarker levels in our investigation, the success or healthiness in military activities is multifactorial and does not depend only on interindividual variability or physical capacity. Conclusions: Monitoring biomarkers and multiple genomic regions can generate more efficient exercise-related phenotype interventions. Full article
(This article belongs to the Special Issue Tactical Athlete Health and Performance)
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11 pages, 1231 KB  
Article
Harnessing Visual Neuroplasticity Through Auditory Biofeedback—Functional and Electrophysiological Gains Across Retinal, Optic-Nerve, and Cortical Visual Impairment: A Prospective Pilot Study
by Marco Zeppieri, Roberta Amato, Daniela Catania, Mutali Musa, Alessandro Avitabile, Fabiana D’Esposito, Caterina Gagliano, Matteo Capobianco and Simonetta Gaia Nicolosi
Clin. Pract. 2025, 15(9), 170; https://doi.org/10.3390/clinpract15090170 - 17 Sep 2025
Viewed by 242
Abstract
Background: This prospective pilot study included four participants with chronic visual impairment and assessed functional and electrophysiological recovery following visual evoked potential (VEP)-guided auditory biofeedback across diverse etiologies. Low vision affects more than two billion people worldwide and imposes a sustained personal and [...] Read more.
Background: This prospective pilot study included four participants with chronic visual impairment and assessed functional and electrophysiological recovery following visual evoked potential (VEP)-guided auditory biofeedback across diverse etiologies. Low vision affects more than two billion people worldwide and imposes a sustained personal and socioeconomic burden. Conventional rehabilitation emphasizes optical aids and environmental modification without directly stimulating the visual pathway. Emerging evidence indicates that auditory biofeedback based on real-time cortical activity can leverage adult neuroplasticity. Methods: Four men (mean age 58 ± 12 years) with chronic visual impairment attributable to occipital stroke, stage IV macular hole, end-stage open-angle glaucoma, or diabetic maculopathy completed ten 10-min monocular sessions with the Retimax Vision Trainer over three weeks (15 Hz pattern reversal, 90% contrast). Primary end points were best corrected visual acuity (BCVA, ETDRS letters) and P100 amplitude/latency. Fixation stability was recorded with MAIA microperimetry when feasible. A focused PubMed review (2010–2025) mapped current evidence and research gaps. Results: Median BCVA improved by seven letters (IQR 0–15); three of eight eyes gained ≥ 10 letters and none lost vision. Mean P100 amplitude increased from 1.0 ± 1.2 µV to 3.0 ± 1.1 µV, while latency shortened by 3.9 ms. Electrophysiological improvement paralleled behavioural gain irrespective of lesion site. No adverse events occurred. Conclusions: A concise course of VEP-guided auditory biofeedback produced concordant functional and neurophysiological gains across retinal, optic nerve, and cortical pathologies. These pilot data support integration of closed-loop biofeedback into routine low vision care and justify larger sham-controlled trials. Full article
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16 pages, 302 KB  
Article
Prognostic Value of FasL, BDNF, and IL-1β as Predictors of Therapeutic Response in Schizophrenia
by Zofia Szymona-Kuciewicz, Maja Owe-Larsson, Marta Flis, Hanna Karakula-Juchnowicz, Barbara Zdzisinska, Ewa Dudzinska, Ewa M. Urbanska and Kinga Szymona
J. Clin. Med. 2025, 14(18), 6417; https://doi.org/10.3390/jcm14186417 - 11 Sep 2025
Viewed by 285
Abstract
Background/Objectives: Pro-inflammatory, neurotrophic, and proapoptotic factors affect the course of schizophrenia; however, their impact on the clinical response during relapse is not well recognized. A member of TNF family, Fas ligand (FasL), participates in apoptosis, but its connection with treatment-resistant schizophrenia is [...] Read more.
Background/Objectives: Pro-inflammatory, neurotrophic, and proapoptotic factors affect the course of schizophrenia; however, their impact on the clinical response during relapse is not well recognized. A member of TNF family, Fas ligand (FasL), participates in apoptosis, but its connection with treatment-resistant schizophrenia is unknown. Methods: For this preliminary exploratory study, 53 patients with schizophrenia relapse and 45 healthy subjects were enrolled. Pro-inflammatory interleukin IL-1β, brain-derived neurotrophic factor (BDNF), FasL levels, and clinical evaluations (PANSS, SANS, SAPS) were studied at admission, after a 4-week therapy, and at remission. Results: In the clozapine-treated therapy-resistant group, IL-1β correlated negatively with clinical improvement (admission, 4-week treatment). In patients not treated with clozapine, IL-1β correlated negatively with disease duration (admission). A negative correlation occurred between FasL and clinical improvement in general symptoms (admission, 4-week treatment), FasL and leukocyte count (admission), and IL-1β and BDNF levels (4-week treatment). In the clozapine-treated group, the negative correlation between FasL levels and the leukocyte count was absent. Conclusions: The severity of psychopathology in patients with schizophrenia seems to correlate with higher IL-1β and lower BDNF. The novelty of our findings is the observation that higher FasL is negatively associated with the degree of clinical improvement. Thus, a decline of FasL during treatment may be proposed as a predictor of clinical recovery. With caution, we suggest that clozapine use may be linked to a protective effect against FasL signaling and the alleviation of apoptotic processes. Full article
11 pages, 794 KB  
Article
Identifying the Need for Prehabilitation in Cancer Patients Undergoing Nephrectomy or Nephroureterectomy
by Bente Thoft Jensen, Peter Blak Hjort, Kathrine Melchiorsen, Henriette Vind Thaysen, Ida Larsen, Mai Lorenzen, Rikke Knudsen and Anna K. Keller
Cancers 2025, 17(17), 2939; https://doi.org/10.3390/cancers17172939 - 8 Sep 2025
Viewed by 424
Abstract
Background: The potential benefits of prehabilitation in patients undergoing surgery for renal cell carcinoma (RCC) or upper-tract urothelial carcinoma (UTUC) remain unknown. The aim was to evaluate physical function and baseline characteristics over the course of treatment to identify a potential need for [...] Read more.
Background: The potential benefits of prehabilitation in patients undergoing surgery for renal cell carcinoma (RCC) or upper-tract urothelial carcinoma (UTUC) remain unknown. The aim was to evaluate physical function and baseline characteristics over the course of treatment to identify a potential need for prehabilitation. Methods: In this prospective observational study, 62 patients were enrolled—31 undergoing nephrectomies for RCC and 31 undergoing nephroureterectomy for UTUC. Baseline assessments included nutritional screening (NRS 2002), frailty (Clinical Frailty Scale), hemoglobin and iron levels, smoking status, and physical function using the Six-Minute Walk Test (6MWT) and the 30-Second Sit-to-Stand Test (30STS). Functional tests were repeated at hospital discharge and at two-week postoperative follow-up visit. Results: At baseline, 45% of RCC and 68% of UTUC patients were at nutritional risk. Preoperative frailty was present in 20% of the cohort, and 53% had anemia. Functional impairment below the lower limit values (LLVs) was observed in 16% for the RCC and 36% of the UTUC, assessed by 6MWT. The 30 STS revealed that 58% of RCC and 42% of UTUC were below LLV. At discharge, impairment peaked, with 59% and 82% of patients being below the LLVs, respectively. Functional performance partially recovered at follow-up but did not return to baseline levels. Conclusions: Preoperative nutritional deficits, anemia, and functional impairment are prevalent in patients undergoing nephrectomy or nephroureterectomy. A marked postoperative functional decline was identified postoperatively supporting a potential need for early individualized prehabilitation strategies to improve recovery in patients undergoing kidney cancer surgery. Full article
(This article belongs to the Special Issue Clinical Treatment and Prognostic Factors of Urologic Cancer)
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23 pages, 959 KB  
Systematic Review
Systemic Lupus Erythematosus in Pregnancy
by Angeliki Gerede, Efthymios Oikonomou, Sofoklis Stavros, Anastasios Potiris, Panagiota Papasozomenou, Menelaos Zafrakas, Ekaterini Domali, Nikolaos Nikolettos and Makarios Eleutheriades
Med. Sci. 2025, 13(3), 174; https://doi.org/10.3390/medsci13030174 - 4 Sep 2025
Viewed by 587
Abstract
Background/Objectives: The reciprocal relationship between Systemic Lupus Erythematosus (SLE) and pregnancy continues to elude the scientific community’s approaches for a clear understanding. Multiple studies have reached dissimilar results regarding the impact that SLE exerts on pregnancy, whilst the potential risks of lupus pregnancies [...] Read more.
Background/Objectives: The reciprocal relationship between Systemic Lupus Erythematosus (SLE) and pregnancy continues to elude the scientific community’s approaches for a clear understanding. Multiple studies have reached dissimilar results regarding the impact that SLE exerts on pregnancy, whilst the potential risks of lupus pregnancies continue to encumber women of childbearing age. Whether SLE predisposes to a complicated pregnancy and conversely whether pregnancy impacts the progression of the disease is aimed to be assessed by this systematic review. Methods: A thorough search of original research articles was conducted using online databases (PubMed, Google Scholar), initially identifying 877 potential studies. Results: Upon further assessment for relevance and eligibility, 65 articles were selected for detailed analysis. Conclusions: We concluded that, even though advanced approaches have optimized SLE prognosis and treatment, the complexity of the disease requires further extensive study in order to grasp the mechanism behind the susceptibility to adverse complications. SLE pregnancy cannot be considered without risk. Comprehensive, multidisciplinary, and continuous monitoring of the disease course prior to, during, and after pregnancy is necessary to ensure optimal recovery and minimal maternal and fetal complications. Tailored treatments and novel biomarkers would move us towards precise patient-centered care that addresses each patient’s unique disease profile and pregnancy needs, ultimately improving both maternal and fetal outcomes in women with systemic lupus erythematosus. Full article
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13 pages, 2811 KB  
Systematic Review
Traumatic Bilateral Lumbosacral Jumped Facet Without Fracture in Childhood: Case Report and Systematic Review
by Maria Ilaria Borruto, Michele Pomponi, Calogero Velluto, Achille Marciano, Luca Proietti and Laura Scaramuzzo
J. Clin. Med. 2025, 14(17), 6228; https://doi.org/10.3390/jcm14176228 - 3 Sep 2025
Viewed by 440
Abstract
Background/Objectives: Traumatic dislocation of the lumbosacral facet joints without associated fractures is exceedingly rare in the pediatric population. Due to the unique anatomical and biomechanical features of the pediatric spine, such injuries present diagnostic and therapeutic challenges. This study aims to describe a [...] Read more.
Background/Objectives: Traumatic dislocation of the lumbosacral facet joints without associated fractures is exceedingly rare in the pediatric population. Due to the unique anatomical and biomechanical features of the pediatric spine, such injuries present diagnostic and therapeutic challenges. This study aims to describe a rare case of bilateral L5–S1 jumped facets without fracture in a 13-year-old boy and to review the existing literature on pediatric traumatic facet dislocations. Methods: We performed a systematic review according to PRISMA guidelines, searching PubMed, Embase, Scopus, and the Cochrane Library up to 16 January 2025. Keywords included “pediatric traumatic spondylolisthesis” and “pediatric traumatic facet joint”. Eligible studies reported traumatic lumbosacral or thoracolumbar facet dislocations in patients aged <18 years. In addition, we report the clinical course, surgical management, and outcome of a representative case from our institution. Results: The systematic review identified 14 pediatric cases across 11 studies. Most patients were male (71.4%), with high-energy trauma as the primary mechanism. The L5–S1 level was most frequently involved (57.1%). Neurological impairment was present in 57.1% of cases. All patients underwent surgical treatment, with posterior fixation being the most common approach. Our case involved bilateral L5–S1 jumped facets without fracture, successfully treated with open reduction and posterior fusion. Postoperative recovery was favorable, with neurological improvement. Conclusions: Traumatic bilateral facet dislocation without fracture is an extremely rare but serious condition in pediatric patients. Early recognition and surgical stabilization are essential to prevent permanent neurological damage. This study reinforces the importance of advanced imaging and prompt multidisciplinary management in optimizing outcomes. Full article
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21 pages, 820 KB  
Review
Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Pathophysiology, Clinical Patterns, and Therapeutic Challenges of Intractable and Severe Forms
by Tatsuro Misu
Int. J. Mol. Sci. 2025, 26(17), 8538; https://doi.org/10.3390/ijms26178538 - 2 Sep 2025
Viewed by 1382
Abstract
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is characterized by the predominance of optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), and cortical encephalitis, and can be diagnosed by the presence of pathogenic immunoglobulin G (IgG) antibodies targeting the extracellular domain of MOG in [...] Read more.
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is characterized by the predominance of optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), and cortical encephalitis, and can be diagnosed by the presence of pathogenic immunoglobulin G (IgG) antibodies targeting the extracellular domain of MOG in the serum and cerebrospinal fluid (CSF). Initially considered a variant of multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), it is now widely recognized as a separate entity, supported by converging evidence from serological, pathological, and clinical studies. Patients with MOGAD often exhibit better recovery from acute attacks; however, their clinical and pathological features vary based on the immunological role of MOG-IgG via antibody- or complement-mediated perivenous demyelinating pathology, in addition to MOG-specific cellular immunity, resulting in heterogeneous demyelinated lesions from vanishing benign forms to tissue necrosis, even though MOGAD is not a mild disease. The key is the immunological mechanism of devastating lesion coalescence and long-term degenerating mechanisms, which may still accrue, particularly in the relapsing, progressing, and aggressive clinical course of encephalomyelitis. The warning features of the severe clinical forms are: (1) fulminant acute multifocal lesions or multiphasic ADEM transitioning to diffuse (Schilder-type) or tumefactive lesions; (2) cortical or subcortical lesions related to brain atrophy and/or refractory epilepsy (Rasmussen-type); (3) longitudinally extended spinal cord lesions severely affected with residual symptoms. In addition, it is cautious for patients refractory to acute stage early 1st treatment including intravenous methylprednisolone treatment and apheresis with residual symptoms and relapse activity with immunoglobulin and other 2nd line treatments including B cell depletion therapy. Persistent MOG-IgG high titration, intrathecal production of MOG-IgG, and suggestive markers of higher disease activity, such as cerebrospinal fluid interleukin-6 and complement C5b-9, could be identified as promising markers of higher disease activity, worsening of disability, and poor prognosis, and used to identify signs of escalating treatment strategies. It is promising of currently ongoing investigational antibodies against anti-interleukin-6 receptor and the neonatal Fc receptor. Moreover, due to possible refractory issues such as the intrathecal production of autoantibody and the involvement of complement in the worsening of the lesion, further developments of other mechanisms of action such as chimeric antigen receptor T-cell (CAR-T) and anti-complement therapies are warranted in the future. Full article
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31 pages, 1533 KB  
Review
Immunodynamic Disruption in Sepsis: Mechanisms and Strategies for Personalized Immunomodulation
by Jhan S. Saavedra-Torres, María Virginia Pinzón-Fernández, Humberto Alejandro Nati-Castillo, Valentina Cadena Correa, Luis Carlos Lopez Molina, Juan Estaban Gaitán, Daniel Tenorio-Castro, Diego A. Lucero Guanga, Marlon Arias-Intriago, Andrea Tello-De-la-Torre, Alice Gaibor-Pazmiño and Juan S. Izquierdo-Condoy
Biomedicines 2025, 13(9), 2139; https://doi.org/10.3390/biomedicines13092139 - 2 Sep 2025
Viewed by 1105
Abstract
Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection. It follows a dynamic course in which early hyperinflammation coexists and overlaps with progressive immune suppression, a process best described as immunodynamic disruption. Key mechanisms include extensive lymphocyte death, expansion [...] Read more.
Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection. It follows a dynamic course in which early hyperinflammation coexists and overlaps with progressive immune suppression, a process best described as immunodynamic disruption. Key mechanisms include extensive lymphocyte death, expansion of regulatory T cells, impaired antigen presentation, and persistent activation of inhibitory checkpoints such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4). These changes reduce immune competence and increase vulnerability to secondary infections. Clinically, reduced expression of Human Leukocyte Antigen–DR (HLA-DR) on monocytes and persistent lymphopenia have emerged as robust biomarkers for patient stratification and timing of immunomodulatory therapies. Beyond the acute phase, many survivors do not achieve full immune recovery but instead develop a Persistent Immune Remnant, defined as long-lasting immune, metabolic, and endothelial dysfunction despite apparent clinical resolution. Recognizing PIR emphasizes the need for long-term monitoring and biomarker-guided interventions to restore immune balance. To integrate these observations, we propose the SIMMP–Sepsis model (Sepsis-Associated Persistent Multiorgan Immunometabolic Syndrome), which links molecular dysfunction to clinical trajectories and provides a framework for developing precision immunotherapies. This perspective reframes sepsis not only as an acute crisis but also as a chronic immunometabolic syndrome, where survival marks the beginning of active immune restoration. Full article
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14 pages, 932 KB  
Article
Strength-Dependent Differences in the Magnitude and Time Course of Post-Activation Performance Enhancement in High Jump Athletes
by Javier Sanchez-Sanchez and Alejandro Rodríguez-Fernández
J. Funct. Morphol. Kinesiol. 2025, 10(3), 333; https://doi.org/10.3390/jfmk10030333 - 29 Aug 2025
Viewed by 591
Abstract
Background: A post-activation performance enhancement (PAPE) can acutely improve explosive actions, but its time course may be influenced by individual strength levels. Objectives: The aim of this study was to analyze the performance responses following three PAPE protocols, considering the strength [...] Read more.
Background: A post-activation performance enhancement (PAPE) can acutely improve explosive actions, but its time course may be influenced by individual strength levels. Objectives: The aim of this study was to analyze the performance responses following three PAPE protocols, considering the strength level as a modulating factor in trained high jump athletes. Methods: Twenty-one male high jumpers (Tier 3) were divided into stronger (SG, n = 10) and weaker (WG, n = 11) groups based on the median load (80 kg) lifted at 0.8 m/s in a velocity-based half-squat test. The participants completed three squat-based PAPE protocols (velocity loss thresholds of 5%, 10%, and 15%) in a randomized, double-blind crossover design. Their performance in a 10 m sprint (S10) and a countermovement jump (CMJ) was assessed at baseline and 0, 4, 8, and 12 min post-intervention. Results: No significant three-way interactions were observed for the S10 or CMJ performance (p > 0.05). The absolute CMJ performance was consistently higher in the SG across all the time points (p < 0.001, d = 1.25, large), with significant peak values observed at 4 min post-activation. However, both groups exhibited transient improvements in their S10 and CMJ performance that were statistically significant (p < 0.05) and of a large magnitude (d = 1.93–3.15), observed at 4 and/or 8 min post-activation, which subsequently declined by 12 min. Conclusions: The strength level modulates both the time course and the magnitude of the PAPE. Stronger athletes responded better to both less and more demanding protocols (5% to 15% velocity loss thresholds) with a 4–8 min recovery, whereas weaker athletes benefited mainly from less demanding stimuli (5% velocity loss thresholds), provided that the recovery was sufficient (≈4 min) to allow potentiation to emerge. However, with more demanding protocols (15% velocity loss thresholds), a longer recovery period (≈8 min) appears necessary. Full article
(This article belongs to the Special Issue Sports-Specific Conditioning: Techniques and Applications)
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17 pages, 2848 KB  
Article
Zileuton Attenuates Acute Kidney Injury in Glycerol-Induced Rhabdomyolysis by Regulating Myeloid-Derived Suppressor Cells in Mice
by Tae Won Lee, Eunjin Bae, Jin Hyun Kim, Myeong Hee Jung and Dong Jun Park
Int. J. Mol. Sci. 2025, 26(17), 8353; https://doi.org/10.3390/ijms26178353 - 28 Aug 2025
Viewed by 543
Abstract
Rhabdomyolysis is characterized by the breakdown of skeletal muscle tissue, frequently leading to acute kidney injury (AKI). Traditional conservative treatments have shown limited effectiveness in modifying the disease course, thereby necessitating targeted pharmacological approaches. Zileuton (Z), a selective inhibitor of 5-lipoxygenase (5-LOX), has [...] Read more.
Rhabdomyolysis is characterized by the breakdown of skeletal muscle tissue, frequently leading to acute kidney injury (AKI). Traditional conservative treatments have shown limited effectiveness in modifying the disease course, thereby necessitating targeted pharmacological approaches. Zileuton (Z), a selective inhibitor of 5-lipoxygenase (5-LOX), has demonstrated efficacy in enhancing renal function recovery in animal models of AKI induced by agents such as cisplatin, aminoglycosides, and polymyxins. The present study aimed to evaluate the therapeutic potential of a single dose of Z in mitigating rhabdomyolysis-induced AKI (RI-AKI) via modulation of myeloid-derived suppressor cells (MDSCs). Male C57BL/6 mice were assigned to four experimental groups: Sham (intraperitoneal administration of 0.9% saline), Z (single intraperitoneal injection of Z at 30 mg/kg body weight), glycerol (Gly; single intramuscular dose of 50% glycerol at 8 mL/kg), and glycerol plus Z (Z + Gly; concurrent administration of glycerol intramuscularly and Z intraperitoneally). Animals were sacrificed 24 h post-glycerol injection for analysis. Zileuton administration significantly improved renal function, as indicated by reductions in blood urea nitrogen (BUN) levels (129.7 ± 17.9 mg/dL in the Gly group versus 101.7 ± 6.8 mg/dL in the Z + Gly group, p < 0.05) and serum creatinine (Cr) levels (2.2 ± 0.3 mg/dL in the Gly group versus 0.9 ± 0.3 mg/dL in the Gly + Z group p < 0.05). Histopathological assessment revealed a marked decrease in tubular injury scores in the Z + Gly group compared to the Gly group. Molecular analyses demonstrated that Z treatment downregulated mRNA expression of macrophage-inducible C-type lectin (mincle) and associated macrophage infiltration-related factors, including Areg-1, Cx3cl1, and Cx3CR1, which were elevated 24 h following glycerol administration. Furthermore, the expression of NLRP-3, significantly upregulated post-glycerol injection, was attenuated by concurrent Z treatment. Markers of mitochondrial biogenesis, such as mitochondrial DNA (mtDNA), transcription factor A mitochondrial (TFAM), and carnitine palmitoyltransferase 1 alpha (CPT1α), were diminished 24 h after glycerol injection; however, their expression was restored upon simultaneous Z administration. Additionally, Z reduced protein levels of BNIP3, a marker of mitochondrial autophagy, while enhancing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), suggesting that Z ameliorates RI-AKI severity through the regulation of mitochondrial quality control mechanisms. Zileuton also decreased infiltration of CD11b(+) Gr-1(+) MDSCs and downregulated mRNA levels of MDSC-associated markers, including transforming growth factor-beta (TGF-β), arginase-1 (Arg-1), inducible nitric oxide synthase (iNOS), and iron regulatory protein 4 (Irp4), in glycerol-injured kidneys relative to controls. These markers were elevated 24 h post-glycerol injection but were normalized following concurrent Z treatment. Collectively, these findings suggest that Zileuton confers reno-protective effects in a murine model of RI-AKI, potentially through modulation of mitochondrial dynamics and suppression of MDSC-mediated inflammatory pathways. Further research is warranted to elucidate the precise mechanisms by which Z regulates MDSCs and to assess its therapeutic potential in clinical contexts. Full article
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11 pages, 3101 KB  
Case Report
Macular Neovascularization in Pediatric Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency: A Retrospective Analysis of a Case Series
by Magdalena Hubert, Maciej Gawęcki and Andrzej Grzybowski
J. Clin. Med. 2025, 14(17), 6062; https://doi.org/10.3390/jcm14176062 - 27 Aug 2025
Viewed by 526
Abstract
Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare autosomal recessive metabolic disorder affecting long-chain fatty acid β-oxidation. A hallmark feature of LCHADD is progressive chorioretinopathy, which may lead to severe visual complications, including macular neovascularization (MNV). The goal of the study was [...] Read more.
Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare autosomal recessive metabolic disorder affecting long-chain fatty acid β-oxidation. A hallmark feature of LCHADD is progressive chorioretinopathy, which may lead to severe visual complications, including macular neovascularization (MNV). The goal of the study was to analyze MNV in patients with genetically confirmed LCHADD. Methods: Data of 8 patients with LCHADD from the Kaszubia region in Poland followed in the clinic were retrospectively analyzed. The analyses included genetic confirmation, ophthalmologic examinations, spectral-domain optical coherence tomography (SD-OCT), and treatment responses. Results: Two patients with MNV in the course of LCHADD were identified. In Patient 1, a 9-year-old female, unilateral MNV at the fibrotic stage with a visual acuity of counting fingers was diagnosed in the right eye. No treatment was administered. The left eye remained stable, maintaining a best corrected visual acuity (BCVA) of 0.9 on the decimal Snellen chart. Patient 2, male, was followed from age 8 to 16 and during that time developed bilateral MNV. The right eye presented with inactive MNV at the age of 9, resulting in BCVA reduction to 0.3 without active fluid, and remained stable without intervention. The left eye developed active MNV at age 15 with subretinal fluid and retinal edema. Treatment with five intravitreal injections of ranibizumab led to complete resolution and recovery of BCVA to 1.0. Conclusions: MNV, although rare, can develop in pediatric LCHADD patients silently and bilaterally. Early detection through regular ophthalmologic screening is crucial, as timely anti-VEGF treatment can preserve or restore vision. Delayed diagnosis may result in irreversible damage and limited therapeutic benefit. Full article
(This article belongs to the Section Ophthalmology)
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13 pages, 507 KB  
Article
Glycocalyx-Shedding and Inflammatory Reactions Occur Yet Do Not Predict Complications Resulting from an Esophagectomy in an Accelerated Recovery After Surgery Program
by Hendrik Drinhaus, Christoph Mallmann, Corvin Cleff, Tobias Neumann, Christina Daniels, Christiane J. Bruns, Andrea U. Steinbicker, Wolfgang Schröder and Thorsten Annecke
J. Clin. Med. 2025, 14(17), 6048; https://doi.org/10.3390/jcm14176048 - 26 Aug 2025
Viewed by 541
Abstract
Background/Objectives: “Accelerated Recovery after Surgery” (ARAS) programs for esophagectomy aim to shorten the perioperative course without increases in morbidity or mortality. In such programs, the prediction and early detection of perioperative complications is essential, as ICU observation times are limited. We evaluated two [...] Read more.
Background/Objectives: “Accelerated Recovery after Surgery” (ARAS) programs for esophagectomy aim to shorten the perioperative course without increases in morbidity or mortality. In such programs, the prediction and early detection of perioperative complications is essential, as ICU observation times are limited. We evaluated two potential laboratory markers as predictors for postoperative complications: shedding of the endothelial glycocalyx and the veno-arterial CO2-gap as indicators of microcirculatory disturbances. Methods: In total, 26 patients undergoing hybrid Ivor Lewis esophagectomy within an ARAS program were included. Macrocirculatory conditions were kept stable by enhanced hemodynamic monitoring (PiCCO). Glycocalyx shedding parameters (Syndecan-1, heparan sulfate, hyaluronic acid) and a panel of inflammatory mediators were measured preoperatively, upon ICU-admission, and on the first postoperative day. The veno-arterial CO2-gap was calculated at induction of anesthesia, during laparoscopy, and upon admission to the ICU. Results: Complications (Dindo-Clavien ≥3) occurred in n = 16 (62%) patients. From preoperatively to admission to the ICU, Syndecan-1 (29 pre-op to 56 ng/mL at ICU-admission) and Interleukins 1b (1.2 to 1.4 pg/mL), 6 (1.3 to 19.9 pg/mL), 8 (5.2 to 19.9 pg/mL), and 10 (0.50 to 1.33 pg/mL) increased, indicating a temporary increase in inflammation and glycocalyx shedding during surgery. A difference between patients with or without complications could not be detected. There was also no difference in the veno-arterial CO2-gap between the two groups (median of 6.8 mmHg in all patients, 6.7 in patients with complications, 7.8 in patients without complications). Conclusions: Signs of microcirculatory dysfunctions and inflammation occurred during esophagectomy within an ARAS protocol with tightly controlled hemodynamics. Increases in Syndecan-1 and the veno-arterial CO2-gap could not predict perioperative complications. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Outcomes and Therapeutic Management)
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9 pages, 5551 KB  
Case Report
Is Semaglutide Linked to NAION? A Case Report on a Rare Ocular Complication
by Dina Lešin Gaćina, Tomislav Vidović, Nikolina Vlajić Oreb, Lovorka Matković and Sonja Jandroković
Reports 2025, 8(3), 149; https://doi.org/10.3390/reports8030149 - 20 Aug 2025
Viewed by 1575
Abstract
Background and Clinical Significance: Ischemic optic neuropathies (IONs) are significant causes of vision loss resulting from compromised blood flow to the optic nerve. Diabetes mellitus (DM) exacerbates the risk of IONs through chronic hyperglycemia and associated vascular dysfunction. Recently, semaglutide, a glucagon-like [...] Read more.
Background and Clinical Significance: Ischemic optic neuropathies (IONs) are significant causes of vision loss resulting from compromised blood flow to the optic nerve. Diabetes mellitus (DM) exacerbates the risk of IONs through chronic hyperglycemia and associated vascular dysfunction. Recently, semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been linked to ocular complications, including non-arteritic anterior ischemic optic neuropathy (NAION), potentially due to the rapid glycemic changes or vascular effects. Case Presentation: A 55-year-old female with type 2 DM, hypertension, and hyperlipidemia presented with blurred vision and optic disc edema after four months of semaglutide therapy (Ozempic®, Sydney, Australia). Initially diagnosed with diabetic papillopathy (DP), her condition progressed to NAION, leading to partial visual recovery with corticosteroid treatment and improved glycemic management. Diagnostic evaluations, including visual field testing, optical coherence tomography, and fluorescein angiography, supported the diagnosis. Conclusions: This case report describes the clinical course of a diabetic patient treated with a semaglutide who developed an ischemic optic event. The timing of symptom onset in relation to the initiation of semaglutide therapy raises the possibility of a causal association between the drug and this rare ocular complication. Close monitoring of ocular health is crucial for patients on GLP-1 receptor agonists, particularly those with pre-existing vascular risk factors. Further research is needed to elucidate the underlying mechanisms and guide clinical practice. Full article
(This article belongs to the Section Ophthalmology)
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36 pages, 1587 KB  
Article
Long-Term Noninvasive Genetic Monitoring Guides Recovery of the Endangered Columbia Basin Pygmy Rabbits (Brachylagus idahoensis)
by Stacey A. Nerkowski, Paul A. Hohenlohe, Janet L. Rachlow, Kenneth I. Warheit, Jonathan A. Gallie and Lisette P. Waits
Genes 2025, 16(8), 956; https://doi.org/10.3390/genes16080956 - 13 Aug 2025
Viewed by 1154
Abstract
Background/Objectives: Loss and fragmentation of habitat from agricultural conversion led to the near extirpation of the pygmy rabbit (Brachylagus idahoensis Merriam, 1891) population in the Columbia Basin (CB) of Washington, USA. Recovery efforts began in 2002 and included captive breeding, translocations from [...] Read more.
Background/Objectives: Loss and fragmentation of habitat from agricultural conversion led to the near extirpation of the pygmy rabbit (Brachylagus idahoensis Merriam, 1891) population in the Columbia Basin (CB) of Washington, USA. Recovery efforts began in 2002 and included captive breeding, translocations from other regions for genetic rescue, and reintroduction into native habitat in three sites: Sagebrush Flat (SBF), Beezley Hills (BH), and Chester Butte (CHB). Methods: We used noninvasive and invasive genetic sampling to evaluate demographic and population genetic parameters on three translocated populations of pygmy rabbits over eight years (2011–2020). For each population, our goal was to use fecal DNA sampling and 19 microsatellite loci to monitor spatial distribution, apparent survival rates, genetic diversity, reproduction, effective population size, and the persistence of CB ancestry. Over the course of this study, 1978 rabbits were reintroduced as part of a cooperative conservation effort between state and federal agencies. Results: Through winter and summer monitoring surveys, we detected 168 released rabbits and 420 wild-born rabbits in SBF, 13 released rabbits and 2 wild-born in BH, and 16 released rabbits in CHB. Observed heterozygosity (Ho) values ranged from 0.62–0.84 (SBF), 0.59–0.80 (BH), and 0.73–0.77 (CHB). Allelic richness (AR) ranged from 4.67–5.35 (SBF), 3.71–5.41 (BH), and 3.69–4.65 (CHB). Effective population (Ne) within SBF varied from 12.3 (2012) to 44.3 (2017). CB ancestry persisted in all three wild populations, ranging from 15 to 27%. CB ancestry persisted in 99% of wild-born juveniles identified in SBF. Apparent survival of juvenile rabbits differed across years (1–39%) and was positively associated with release date, release weight, and genetic diversity. Survival of adults (0–43%) was positively influenced by release day, with some evidence that genetic diversity also positively influenced adult apparent survival. Conclusions: Noninvasive genetic sampling has proven to be an effective and efficient tool in monitoring this reintroduced population, assessing both demographic and genetic factors. This data has helped managers address the goals of the Columbia Basin recovery program of establishing multiple sustainable wild populations within the sagebrush steppe habitat of Washington. Full article
(This article belongs to the Special Issue Advances of Genetics in Wildlife Conservation and Management)
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