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24 pages, 1495 KB  
Review
Inborn Errors of Immunity in Pediatric Hematology and Oncology: Diagnostic Principles for Clinical Practice
by Giulia Roberti, Giulia Maestrini, Beatrice Polito, Leonardo Amato, Eva Parolo, Gabriella Casazza, Rita Consolini and Giorgio Costagliola
J. Clin. Med. 2025, 14(17), 6295; https://doi.org/10.3390/jcm14176295 - 5 Sep 2025
Abstract
Immune dysregulation is being increasingly recognized as a leading sign of a wide spectrum of inborn errors of immunity (IEIs). Therefore, patients with IEIs are frequently managed in non-immunological settings, including hematology and oncology units, during the diagnostic process or follow-up. The most [...] Read more.
Immune dysregulation is being increasingly recognized as a leading sign of a wide spectrum of inborn errors of immunity (IEIs). Therefore, patients with IEIs are frequently managed in non-immunological settings, including hematology and oncology units, during the diagnostic process or follow-up. The most relevant hematological signs associated with IEIs comprise autoimmune cytopenia (AIC), lymphoproliferative diseases (LPD), malignancies, hemophagocytic lymphohystiocitosis (HLH), bone marrow failure (BMF), myelodysplastic syndromes (MDS), and peripheral or tissue eosinophilia. The prognosis of patients with IEIs can significantly improve when a molecular diagnosis is established, as it can allow the use of targeted treatments, guide appropriate follow-up strategies and, in some cases, support the rationale for hematopoietic stem cell transplantation or gene therapy. Therefore, there is an urgent need to recognize the warning signs suggestive for an underlying IEI among patients presenting with common hematological features and to ensure an appropriate diagnostic approach. As a general rule, clinicians should always provide a clinical alert in the presence of two or more IEI-associated hematological signs, as well as a positive familial history for IEI or hematologic immune dysregulation, a personal history of severe infections, and other signs of immune dysregulation. Concerning AIC, an increased likelihood of IEI is characteristic of patients with treatment refractoriness, autoimmune hemolytic anemia, or multilineage cytopenia. In the case of LPD, the main elements of suspicion are represented by the chronic or recurrent disease course, the persistence of Epstein–Barr Virus (EBV) infection, and the development of lymphoproliferation in atypical localizations. Among patients with malignancy, clinicians should investigate for IEI those with rare neoplasia, virus-associated tumors, and an association with syndromic features, while patients with HLH should always receive an immunological assessment when a clear rheumatologic trigger, underlying malignancy, or well-recognized cause is not evident. The case of MDS and BMF is complex, as new monogenic entities are continuously being described. However, it is pivotal to consider the presence of monocytopenia, warts, vasculitis, and neurological disease, as well as specific cytogenetic abnormalities, such as chromosome 7 monosomy, as warning sings for IEIs. Finally, the main red flags for IEIs in patients with eosinophilia are skeletal/facial abnormalities, recurrent abscesses, refractory eczema, organomegaly, or thrombocytopenia. Full article
13 pages, 558 KB  
Article
Epidemiological Changes in Pediatric RSV Infections in Poland (2016–2024): Impact of the COVID-19 Pandemic
by Agnieszka Blomberg, Magdalena Żak, Maria Koźba-Baranowska, Marcin Tkaczyk, Marta Depczyk-Bukała and Krzysztof Zeman
J. Clin. Med. 2025, 14(17), 6284; https://doi.org/10.3390/jcm14176284 - 5 Sep 2025
Abstract
Objective: The COVID-19 pandemic disrupted the seasonal pattern of RSV infections, increasing cases outside the typical epidemic season. This study aimed to assess the pandemic’s impact on the clinical characteristics of RSV infections in children hospitalized at the Polish Mother’s Memorial Health [...] Read more.
Objective: The COVID-19 pandemic disrupted the seasonal pattern of RSV infections, increasing cases outside the typical epidemic season. This study aimed to assess the pandemic’s impact on the clinical characteristics of RSV infections in children hospitalized at the Polish Mother’s Memorial Health Institute in Łódź, based on a 9-year observation period from 2016 to 2024. Methods: A retrospective analysis was conducted on 330 children hospitalized for RSV between 2016 and 2024. Patients were divided into pre-COVID-19 (2016–2020, n = 160) and post-COVID-19 (2021–2024, n = 170) groups. The hospitalization course, the treatment duration, the use of oxygen, antibiotics, systemic steroids, the patient age structure, and risk factors were compared. Results: Following the pandemic, the age profile of hospitalized RSV patients shifted, with more children over 12 months (27% post-COVID-19 vs. 18% pre-COVID-19). RSV hospitalizations increased as COVID-19 cases declined (correlation coefficient: −1.0; p < 0.001). The average hospitalization duration decreased by 1.8 days (p = 0.002). Oxygen therapy was used more frequently post-pandemic (p < 0.001), while antibiotic use decreased (51.75% vs. 81.25%; p < 0.001). No significant difference was observed in ICU transfer rates. Premature infants and children with congenital defects experienced longer hospitalizations, with a stronger correlation noted post-COVID-19 (0.38; p < 0.001). Conclusions: The COVID-19 pandemic changed the profile of children hospitalized with RSV, increasing the proportion of older patients. Despite shorter hospital stays, prematurity and congenital anomalies remained key risk factors for severe disease. Study limitations include its retrospective design, selection bias, and limited socio-demographic and clinical data due to pandemic-related constraints. Full article
(This article belongs to the Section Respiratory Medicine)
23 pages, 16144 KB  
Article
Smart Bluetooth Stakes: Deployment of Soil Moisture Sensors with Rotating High-Gain Antenna Receiver on Center Pivot Irrigation Boom in a Commercial Wheat Field
by Samuel Craven, Austin Bee, Blake Sanders, Eliza Hammari, Cooper Bond, Ruth Kerry, Neil Hansen and Brian A. Mazzeo
Sensors 2025, 25(17), 5537; https://doi.org/10.3390/s25175537 - 5 Sep 2025
Abstract
Realization of the goals of precision agriculture is dependent on prescribing irrigation strategies matched to spatiotemporal variations in soil moisture on commercial farms. However, the scale at which these variations occur is not well understood. A high-spatial-density network of sensors with the ability [...] Read more.
Realization of the goals of precision agriculture is dependent on prescribing irrigation strategies matched to spatiotemporal variations in soil moisture on commercial farms. However, the scale at which these variations occur is not well understood. A high-spatial-density network of sensors with the ability to measure and report data over the course of a growing season is needed. In this work, design of the low-profile Smart Bluetooth Stake spatiotemporal soil moisture mapping system is presented. Smart stakes use Bluetooth Low Energy to communicate 64 MHz soil moisture impedance measurements from ground level to a receiver mounted on the center-pivot irrigation boom and equipped with a rotating high-gain parabolic antenna. Smart stakes can remain in the ground throughout the entire growing season without disrupting farm operations. A system of 86 sensors was deployed on a 50-hectare commercial field near Elberta, Utah, during the final growth stage of a crop of winter wheat. Different receiver antenna configurations were tested over the course of several weeks which included two full irrigation cycles. In the high-gain antenna configuration, data was successfully collected from 75 sensors, with successful packet transmission at ranges of approximately 600 m. Enough data was collected to construct a spatiotemporal moisture map of the field over the course of an irrigation cycle. Smart Bluetooth Stakes constitute an important advance in the spatial density achievable with direct sensors for precision agriculture. Full article
(This article belongs to the Special Issue Feature Papers in Smart Agriculture 2025)
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20 pages, 970 KB  
Review
The Emerging Role of the Gut Microbiome in Cerebral Cavernous Malformation: A New Novel Therapeutic Strategy?
by Hamidreza Sadegh and Jaesung P. Choi
Int. J. Mol. Sci. 2025, 26(17), 8622; https://doi.org/10.3390/ijms26178622 - 4 Sep 2025
Viewed by 223
Abstract
Cerebral cavernous malformation (CCM) is a cluster of abnormal blood vessels in the brain that leads to severe neurological deficits, seizures, and fatal hemorrhagic stroke. Currently, there is no available drug treatment for CCM. Most CCMs are conservatively managed by observing change in [...] Read more.
Cerebral cavernous malformation (CCM) is a cluster of abnormal blood vessels in the brain that leads to severe neurological deficits, seizures, and fatal hemorrhagic stroke. Currently, there is no available drug treatment for CCM. Most CCMs are conservatively managed by observing change in appearance (MRI), recent hemorrhage, or any clinical symptoms. Neurosurgery is the only current treatment option, but it is only effective in a few cases. Since most CCM lesions are surgically inaccessible, when left untreated they lead to severe neurological deficits, seizures, and fatal hemorrhagic stroke. Hence, new non-invasive, safe, and effective treatment strategies are urgently needed. Recent research has identified gut microbiome dysbiosis and its innate immune response as the critical stimulus in experimental CCM pathogenesis, demonstrating the importance of the gut–brain axis in CCM. Importantly, CCM patients also manifest gut microbiome dysbiosis and gut barrier health can impact CCM disease course. This review highlights the emerging involvement of the gut microbiome in CCM pathogenesis and its potential as a therapeutic target. While preclinical data suggest mechanistic links, the lack of clinical intervention studies limits current applicability and underscores the need for translational research. Full article
(This article belongs to the Special Issue Molecular Mechanism and Treatment of Hemangioma)
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9 pages, 619 KB  
Case Report
A Rare Tetrad of Sickle Cell Disease, Vascular Ehlers–Danlos Syndrome, Primary Ciliary Dyskinesia, and Phelan–McDermid Syndrome in a Saudi Child: A Complex Multisystem Pediatric Case Report
by Gassem Gohal
Pediatr. Rep. 2025, 17(5), 89; https://doi.org/10.3390/pediatric17050089 - 4 Sep 2025
Viewed by 102
Abstract
Background: The coexistence of sickle cell disease (SCD), vascular Ehlers–Danlos syndrome (vEDS), primary ciliary dyskinesia (PCD), and Phelan–McDermid syndrome (PMS) in a single pediatric patient is extremely rare and poses substantial diagnostic and management challenges. Case presentation: We report an 8-year-old male from [...] Read more.
Background: The coexistence of sickle cell disease (SCD), vascular Ehlers–Danlos syndrome (vEDS), primary ciliary dyskinesia (PCD), and Phelan–McDermid syndrome (PMS) in a single pediatric patient is extremely rare and poses substantial diagnostic and management challenges. Case presentation: We report an 8-year-old male from Jazan, Saudi Arabia, born to consanguineous parents, with early-onset SCD, followed by the identification of vEDS, PCD, and PMS through clinical presentation and whole exome sequencing. His disease course has been exceptionally severe, marked by monthly hospitalizations, multiple PICU admissions, and a wide spectrum of systemic complications. Conclusions: The coexistence of SCD, vEDS, PCD, and PMS may lead to synergistic vascular, pulmonary, and neurodevelopmental compromise, demanding multidisciplinary long-term management. This case underscores the need for a comprehensive targeted genetic assessment in patients with unusually aggressive or syndromic SCD phenotypes, particularly in regions with high levels of consanguineous marriages. Full article
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26 pages, 1237 KB  
Study Protocol
A Novel Macro-Level Model in Evaluating Health and Safety Training Based on Virtual Reality
by Antonella Pireddu, Claudia Giliberti, Alessandro Innocenti, Carla Simeoni and Michela Bonafede
Int. J. Environ. Res. Public Health 2025, 22(9), 1378; https://doi.org/10.3390/ijerph22091378 - 3 Sep 2025
Viewed by 247
Abstract
This document proposes a new evaluation model to be applied to a training course on health and safety at work based on virtual reality. The model refers to three macro-levels (design, delivery, and evaluation), which extend throughout the training life cycle. At macro [...] Read more.
This document proposes a new evaluation model to be applied to a training course on health and safety at work based on virtual reality. The model refers to three macro-levels (design, delivery, and evaluation), which extend throughout the training life cycle. At macro level 1, design, the quality of the model intended for the virtual reality experience is evaluated, as well as its adaptation to the work environment and its compliance with applicable voluntary and mandatory standards; in macro level 2, delivery, the performance of the model, the individual reactions of users with headsets, their performance and psycho-physical state, the time, and the score achieved are evaluated; in macro level 3, evaluation, the long-term effects of subjective training and the social and economic impact that virtual reality training has had on the organisation are evaluated. The study investigates assessment models for virtual-reality-based occupational health and safety courses and identifies a model outlining general criteria that can be adapted to several types of courses and different work sectors. By examining the typical stages of the training life cycle and drawing on training evaluation models such as Kirkpatrick or Molenda and Information and Communication Technology metrics, the study identifies the key elements for assessing the effectiveness of virtual reality training in occupational health and safety. 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 389
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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17 pages, 1175 KB  
Article
The Prevalence and Drug Susceptibility of Candida Species and an Analysis of Risk Factors for Oral Candidiasis—A Retrospective Study
by Marcin Tkaczyk, Anna Kuśka-Kielbratowska, Jakub Fiegler-Rudol, Wojciech Niemczyk, Anna Mertas, Dariusz Skaba and Rafał Wiench
Antibiotics 2025, 14(9), 876; https://doi.org/10.3390/antibiotics14090876 - 30 Aug 2025
Viewed by 353
Abstract
Background: Oral candidiasis is a prevalent opportunistic infection, predominantly caused by Candida albicans (CA), though non-albicans Candida (NAC) species are increasing worldwide. This study aimed to characterize the prevalence of Candida species, evaluate antifungal susceptibility, and identify predisposing risk factors in [...] Read more.
Background: Oral candidiasis is a prevalent opportunistic infection, predominantly caused by Candida albicans (CA), though non-albicans Candida (NAC) species are increasing worldwide. This study aimed to characterize the prevalence of Candida species, evaluate antifungal susceptibility, and identify predisposing risk factors in patients with oral mucosal candidiasis. Methods: A retrospective review of 1286 electronic patient medical records (788 women, 498 men) from 2018 to 2022 was conducted at the Department of Periodontal and Oral Mucosa Diseases, Medical University of Silesia. Swabs from the oral cavity were processed to identify Candida strains by mass spectrometry, followed by drug susceptibility testing for amphotericin B, nystatin, flucytosine, econazole, ketoconazole, miconazole, and fluconazole. Relevant local and systemic predisposing factors were recorded and analyzed statistically. Results: Among 958 patients with positive fungal cultures, CA accounted for 66.79% of isolates, while NAC constituted 33.21%. Multi-strain infections were detected in 8.46% of patients. CA showed lower resistance (<10%) to amphotericin B, nystatin, and flucytosine, but up to 30% resistance to azoles. NAC strains demonstrated elevated resistance rates (>40% for most azoles), with C. krusei exhibiting the highest resistance to the previously mentioned antifungal agents. Key risk factors included wearing removable dentures (p = 0.042) and uncontrolled diabetes mellitus (p = 0.0431). Additional factors, including poor oral hygiene, reduced salivary flow, and immunosuppressive conditions, further increased infection risk. Patients presenting with multiple risk factors were more likely to have multi-strain infections and more severe disease courses. Conclusions: This retrospective analysis highlights the growing prevalence of NAC, rising antifungal resistance (particularly to azoles), and the importance of identifying risk factors, especially denture use and poor glycemic control. Enhanced preventive strategies, robust diagnostic approaches, and optimized antifungal regimens are essential to address this evolving clinical challenge. Full article
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8 pages, 757 KB  
Case Report
Hyponatremia Due to VZV-Induced SIADH in an Older Patient: Case Report and Literature Review
by Zuzanna Żak-Skryśkiewicz, Patrycja Krupińska, Carlo Bieńkowski and Przemysław Witek
Infect. Dis. Rep. 2025, 17(5), 106; https://doi.org/10.3390/idr17050106 - 30 Aug 2025
Viewed by 272
Abstract
Introduction: Hyponatremia is a common finding in hospitalized patients, especially the elderly. Symptoms of hyponatremia can vary depending on the concentration of sodium in serum as well as the dynamics of its escalation. Hyponatremia can have many etiologies, including medication, vomiting, or diarrhea, [...] Read more.
Introduction: Hyponatremia is a common finding in hospitalized patients, especially the elderly. Symptoms of hyponatremia can vary depending on the concentration of sodium in serum as well as the dynamics of its escalation. Hyponatremia can have many etiologies, including medication, vomiting, or diarrhea, and central nervous system disorders, including tumors, trauma, and infections. Case report: In this case, we present a 74-year-old patient who was admitted to the Department of Internal Medicine with symptomatic, acute, and severe hyponatremia in the course of the syndrome of inappropriate antidiuretic hormone secretion due to varicella zoster virus meningoencephalitis. Clinical improvement and normalization of natremia occurred after the initiation of causal treatment. Conclusion: Given the complexity of the potential causes of hyponatremia and the variety of treatments available, it is essential to thoroughly consider the possible reasons for electrolyte abnormalities, including uncommon ones such as central nervous system infections. Full article
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14 pages, 1359 KB  
Article
IL-24 in COVID-19 Patients: Correlations with Disease Progression
by Richard Vollenberg, Katharina Schütte-Nütgen, Markus Strauss, Jonel Trebicka, Julia Fischer and Phil-Robin Tepasse
Int. J. Mol. Sci. 2025, 26(17), 8403; https://doi.org/10.3390/ijms26178403 - 29 Aug 2025
Viewed by 209
Abstract
Interleukin-24 (IL-24) is a cytokine known for its role in immune regulation and apoptosis, with potential implications in viral infections like COVID-19. This study aimed to investigate the association between IL-24 serum levels and the severity of COVID-19 disease. In this prospective bi-center [...] Read more.
Interleukin-24 (IL-24) is a cytokine known for its role in immune regulation and apoptosis, with potential implications in viral infections like COVID-19. This study aimed to investigate the association between IL-24 serum levels and the severity of COVID-19 disease. In this prospective bi-center cross-sectional study, we enrolled 41 COVID-19 patients from two hospitals in Germany. Serial blood samples were collected from a subset of patients, resulting in 88 total blood samples. Patients were categorized into critical, severe, moderate, and mild disease groups based on WHO criteria. IL-24 serum levels were measured during the acute or convalescent phase using an ELISA assay. Inflammatory markers, and kidney and liver function parameters were also evaluated. Statistical analysis included non-parametric tests and correlation analysis. Elevated IL-24 serum levels were observed in ambulant patients (mild disease), compared to hospitalized patients (critical, severe, moderate disease, p < 0.05). IL-24 levels were also significantly higher in patients without oxygenation disorder compared to those with oxygenation therapy (p < 0.05). A negative correlation was found between IL-24 levels and markers of inflammation and liver/kidney function. Elevated IL-24 serum levels were associated with milder COVID-19 courses, suggesting a protective role in modulating immune responses and promoting antiviral apoptosis. Conversely, reduced IL-24 in severe cases may reflect impaired immune regulation, highlighting its potential as a biomarker and therapeutic target. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology (6th Edition))
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16 pages, 287 KB  
Article
Prevalence, Severity, Concomitant Factors, and Natural Trajectory of Insomnia in Patients with Long COVID
by Jamie Hansel Robinson, Halle Bakir, Alicia Shanti James, Marquita S. Brooks, Stephen J. Thomas and Kristine L. Lokken
J. Clin. Med. 2025, 14(17), 6114; https://doi.org/10.3390/jcm14176114 - 29 Aug 2025
Viewed by 348
Abstract
Background/Objective: Insomnia is a clinically important symptom in Long COVID; however, few studies have addressed the presentation and course of insomnia symptoms in patients with Long COVID. Methods: The Insomnia Severity Index (ISI) was administered as part of a comprehensive baseline neuropsychological evaluation [...] Read more.
Background/Objective: Insomnia is a clinically important symptom in Long COVID; however, few studies have addressed the presentation and course of insomnia symptoms in patients with Long COVID. Methods: The Insomnia Severity Index (ISI) was administered as part of a comprehensive baseline neuropsychological evaluation (Time 1) for patients with Long COVID at an Academic Medical Center (AMC). Data were gathered on 172 consecutively referred patients between the dates of November 2020 and May 2022. The mean age of patients at Time 1 was 49 years (range: 18 to 78), with a mean of 15 years of education. Patients were 70% female and 30% male and identified as White/Caucasian (78%), Black/African American (21%), or American Indian (1%). Patients’ severity of COVID-19 infection and self-reported emotional, somatic, cognitive, and fatigue symptoms were also gathered to identify concomitant risk factors for insomnia in Long COVID. Patients were then followed to observe the natural trajectory of insomnia complaints in Long COVID, with the Time 2 evaluation a mean of 9 months after the Time 1 evaluation. Results: Seventy-eight percent of Long COVID patients reported insomnia symptoms at Time 1, with 30% reporting Subthreshold Insomnia symptoms (ISI Score = 8–14), 30% reporting Moderate Insomnia symptoms (ISI Score = 15–21), and 18% reporting Severe Clinical Insomnia (ISI Score = 22–28). Severity of acute COVID-19 infection was not correlated with severity of insomnia in Long COVID; however, being non-white (r = 0.24, n = 172, p < 0.01) and having higher self-reported levels of anxiety (r = 0.41, n = 172, p < 0.01), depression (r = 0.52, n = 172, p < 0.01), perceived stress (r = 0.38, n = 172, p < 0.01), somatic symptoms (r = 0.51, n = 172, p < 0.01), cognitive failures, and fatigue were significantly correlated with insomnia symptoms. Insomnia was also significantly correlated with lower global cognitive function (r = 0.51, n = 172, p < 0.01) and lower cognitive flexibility (r = −0.17, n = 172, p < 0.05). There was a statistically significant decrease in reported ISI scores from Time 1 to Time 2 (t = −3.04; p = 0.003); however, ISI mean scores at both Time 1 (ISI Score = 14) and Time 2 (ISI Score = 12) remained in the Subthreshold Insomnia range (ISI score 8–14). Conclusions: Findings suggest that a large majority of Long COVID patients experience insomnia symptoms. Additionally, insomnia symptoms did not dissipate over time in a clinically meaningful way and were highly correlated with reduced global cognitive function, reduced cognitive flexibility, and higher levels of reported mood symptoms, fatigue, somatic symptoms, and experience of cognitive failures. Thus, there is a pressing need for intervention strategies to treat insomnia in Long COVID patients. Full article
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 301
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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29 pages, 2956 KB  
Article
The Influence of Anti-C3aR and Anti-C5aR Antibody Levels on the Course of Specific Glomerulonephritis Types
by Maciej Szymczak, Harald Heidecke, Marcelina Żabińska, Łucja Janek, Jakub Wronowicz, Krzysztof Kujawa, Kai Schulze-Forster, Karolina Marek-Bukowiec, Tomasz Gołębiowski and Mirosław Banasik
J. Clin. Med. 2025, 14(17), 6082; https://doi.org/10.3390/jcm14176082 - 28 Aug 2025
Viewed by 405
Abstract
Background: The complement system factors’ role in the pathogenesis of autoimmunological diseases is known, but the influence of autoantibodies against complement factors’ receptors on the course of specific glomerular diseases remains unclear. Methods: We measured the levels of anti-C3aR and anti-C5aR [...] Read more.
Background: The complement system factors’ role in the pathogenesis of autoimmunological diseases is known, but the influence of autoantibodies against complement factors’ receptors on the course of specific glomerular diseases remains unclear. Methods: We measured the levels of anti-C3aR and anti-C5aR antibodies in patients with membranous nephropathy (n = 18), primary focal and segmental glomerulosclerosis (FSGS) (n = 25), lupus nephritis (LN) (n = 17), IgA nephropathy (n = 14), mesangial proliferative (non-IgA) glomerulonephritis (n = 6), c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis (n = 40), and p (perinuclear)-ANCA vasculitis (n = 16). These conditions were compared to a healthy control group (n = 22). Then, for up to two years, we tracked the patients’ clinical progress (in terms of creatinine, total protein, and albumin levels) and compared the outcomes with their antibody levels. Results: The lupus nephritis group had higher levels of anti-C3aR and anti-C5aR antibodies than the other groups. The lupus nephritis group’s anti-C3aR antibody level showed a negative correlation with albumin and total protein at several time points of observation. Additionally, at numerous observational points, the anti-C3aR antibody level showed a positive correlation with both the basic albumin level in the FSGS group and the total protein level. Conclusions: The anti-C3aR and anti-C5aR antibodies are higher in lupus nephritis patients compared to other glomerulonephritis patients and healthy individuals. Albumin and total protein levels appear to be correlated positively with anti-C3aR antibody levels in FSGS and negatively in lupus nephritis. Full article
(This article belongs to the Section Nephrology & Urology)
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16 pages, 289 KB  
Review
The Controversies in the Relationship Between Helicobacter pylori Infection and Inflammatory Bowel Disease: Narrative Review
by Jonatan Vukovic and Ivana Jukic
J. Clin. Med. 2025, 14(17), 6083; https://doi.org/10.3390/jcm14176083 - 28 Aug 2025
Viewed by 631
Abstract
Background/Objective: The relationship between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD) remains controversial. While H. pylori is a well-established pathogen in gastroduodenal diseases, emerging evidence suggests it may exert immunomodulatory effects that influence the pathogenesis [...] Read more.
Background/Objective: The relationship between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD) remains controversial. While H. pylori is a well-established pathogen in gastroduodenal diseases, emerging evidence suggests it may exert immunomodulatory effects that influence the pathogenesis and clinical course of IBD. This review aims to explore the association between H. pylori infection and IBD, focusing on infection prevalence among IBD patients, the potential protective or harmful roles of H. pylori, and the impact of eradication therapy on IBD onset and activity. Methods: A comprehensive literature search was conducted using PubMed up to, including clinical studies, meta-analyses, systematic reviews, and observational data. A total of 40 studies met the inclusion criteria and were critically reviewed. Results: The majority of studies indicate a significantly lower prevalence of H. pylori infection among patients with IBD compared to the general population. Several meta-analyses support a potential protective effect, particularly in Crohn’s disease and among CagA-positive H. pylori strains. However, data on the impact of eradication therapy on IBD progression remain inconclusive. Some studies suggest a higher relapse risk post-eradication, while others report no change in disease activity. Variability in outcomes may be influenced by geographic, demographic, and methodological differences, as well as disease activity at the time of eradication. Conclusions: Although numerous studies support an inverse association between H. pylori infection and IBD, the nature and direction of this relationship remain unclear. Given the complex interplay between host immunity, gut microbiota, and antibiotic exposure, the decision to eradicate H. pylori in IBD patients should be individualized. Further prospective studies are needed to clarify the immunological and microbiological mechanisms underlying this association and to inform clinical guidelines. Full article
(This article belongs to the Special Issue Clinical Advances in Gastrointestinal Inflammation)
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 433
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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