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Search Results (55,718)

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Keywords = severe%20disease

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21 pages, 873 KB  
Review
Assessing Quality of Life in Genetic Cardiomyopathies: A Scoping Review
by Lucrezia Tomberli, Fausto Barlocco, Annariina Koivu, Jari Hyttinen, Iacopo Olivotto and Enrica Ciucci
Int. J. Environ. Res. Public Health 2026, 23(7), 833; https://doi.org/10.3390/ijerph23070833 (registering DOI) - 25 Jun 2026
Abstract
Genetic cardiomyopathies (GCMs) are chronic heart muscle disorders requiring lifelong monitoring and treatment. Although quality of life (QoL) and health-related quality of life (HRQoL) are increasingly recognized as important outcomes in cardiomyopathy care, their conceptualization and measurement remain inconsistent. This scoping review aims [...] Read more.
Genetic cardiomyopathies (GCMs) are chronic heart muscle disorders requiring lifelong monitoring and treatment. Although quality of life (QoL) and health-related quality of life (HRQoL) are increasingly recognized as important outcomes in cardiomyopathy care, their conceptualization and measurement remain inconsistent. This scoping review aims to (a) identify the tools most commonly used to assess QoL and HRQoL in adults with genetic cardiomyopathies and (b) map the thematic areas of existing studies, including symptom burden, psychological distress, diagnostic challenges, and the impact of medical and psychological interventions. PubMed, Scopus, and PsycINFO were systematically searched, and the final search was completed in November 2025. Seventeen peer-reviewed studies met the inclusion criteria and were included in this scoping review. The review followed the PRISMA extension for Scoping Reviews and included both quantitative, qualitative and mixed-methods designs. Most studies employed standardized tools such as EQ-5D (N = 5), SF-36/SF36v2 (N = 5), and the Kansas City Cardiomyopathy Questionnaire (N = 3), while others included the Minnesota Living with Heart Failure Questionnaire (N = 2) and disease-specific or ad hoc measures. The most frequently investigated themes included impairments in physical functioning, emotional well-being, symptom burden, psychological distress, and social participation. Several studies showed that patients’ perceived QoL was more closely associated with symptom burden and psychological adjustment than with objective clinical indicators alone. Clinical interventions showed mixed or limited effects on QoL and HRQoL outcomes, even when clinical parameters improved. Qualitative research further emphasized the lived experiences of patients and families, highlighting unmet needs in care. Less commonly addressed findings concerned caregiver perspectives, patient–provider communication, treatment adherence, socioeconomic disadvantage, healthcare costs, productivity loss, and the experiences of patients with rarer cardiomyopathy-related conditions. The results highlight how QoL and HRQoL are central but still inconsistently assessed outcomes in cardiomyopathy research. This review calls for greater conceptual clarity between QoL and HRQoL, greater standardization in measurement tools, broader inclusion of psychosocial variables, and more patient-centred research approaches to better support individuals living with cardiomyopathies. Full article
(This article belongs to the Section Behavioral and Mental Health)
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12 pages, 788 KB  
Communication
Cytokine Profiles in Patients with Type 2 Diabetes Across Different Durations of the Disease: An Exploratory Cross-Sectional Study
by Bernard Kordas, Jan Banach and Judyta K. Juranek
Curr. Issues Mol. Biol. 2026, 48(7), 651; https://doi.org/10.3390/cimb48070651 (registering DOI) - 25 Jun 2026
Abstract
Type 2 diabetes (T2D) is often accompanied by chronic low-grade inflammation, with altered cytokine balance. Although cytokine profiles have often been compared between patients with T2D and healthy individuals, less is known about how they differ among patients with varying disease duration. The [...] Read more.
Type 2 diabetes (T2D) is often accompanied by chronic low-grade inflammation, with altered cytokine balance. Although cytokine profiles have often been compared between patients with T2D and healthy individuals, less is known about how they differ among patients with varying disease duration. The aim of this exploratory study was to compare selected pro-inflammatory and anti-inflammatory cytokines in patients with shorter and longer duration of clinically diagnosed T2D. Anonymized surplus serum samples from 18 patients with T2D were analyzed. Patients were divided into two groups according to disease duration: 1–7 years and 8–16 years post-T2D diagnosis. Serum concentrations of six pro-inflammatory cytokines (IL-1β, IL-5, IL-6, IL-8, TNF-α and IFN-γ), three cytokines with anti-inflammatory or immunoregulatory functions (IL-2, IL-4, IL-10), and pro- and anti-inflammatory ratios were measured. All tests were performed using MAGLUMI X8 (Snibe Diagnostics, Shenzhen, China) high-sensitivity chemiluminescent immunoassay according to the manufacturer’s guidelines. Statistical analysis of the data obtained was performed using GraphPad Prism (Boston, MA, USA). The longer-duration T2D group showed higher median concentrations of several pro-inflammatory cytokines, particularly IL-6, IL-8, TNF-α, and IFN-γ, compared with the shorter-duration group. Several values in the longer-duration group exceeded the assay-specific reference intervals provided by the diagnostic platform. Anti-inflammatory and immunoregulatory cytokines showed less consistent differences between groups. Correlation analysis indicated stronger correlations among pro-inflammatory cytokines than among anti-inflammatory or immunoregulatory cytokines. This cross-sectional study suggests that cytokine profiles may differ between patients with shorter and longer durations of T2D, with a pattern consistent with a more pro-inflammatory profile in the longer-duration group. Because of the small sample size, absence of healthy controls, and limited availability of clinical covariates, these findings should be interpreted as descriptive rather than confirmatory and require validation in larger, longitudinal studies with detailed metabolic characterization. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disease)
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18 pages, 331 KB  
Review
RSV Immunoprophylaxis in Infants and Children: Old Standards, New Agents and the Complexities Therein
by Bosco A. Paes, Paolo Manzoni, John R. Fullarton, Barry S. Rodgers-Gray and Xavier Carbonell-Estrany
Vaccines 2026, 14(7), 556; https://doi.org/10.3390/vaccines14070556 (registering DOI) - 25 Jun 2026
Abstract
Every year, respiratory syncytial virus (RSV) causes an estimated 33 million lower respiratory tract infections in children under five years of age, driving millions of hospitalizations worldwide and substantial mortality in developing countries. For 28 years, the monoclonal antibody (mAb) palivizumab has been [...] Read more.
Every year, respiratory syncytial virus (RSV) causes an estimated 33 million lower respiratory tract infections in children under five years of age, driving millions of hospitalizations worldwide and substantial mortality in developing countries. For 28 years, the monoclonal antibody (mAb) palivizumab has been the principal agent for RSV immunoprophylaxis, reducing hospitalization in defined high-risk groups through monthly intramuscular dosing. The recent approval of two second-generation long-acting mAbs, nirsevimab and clesrovimab, and maternal preF vaccine has fundamentally changed the RSV prevention landscape. In contrast to palivizumab, the long-acting mAbs offer single-dose seasonal protection across a broader infant population, enabling universal immunization programmes for the first time. In this review, we conjointly examine nirsevimab and clesrovimab across their mechanisms of action, pharmacokinetics, efficacy, safety and cost-effectiveness, using palivizumab as the reference standard. Cross-trial efficacy comparisons are complicated by differences in study populations and endpoint definitions; however, when these factors are considered, the available evidence suggests that all three agents offer broadly comparable protection against severe RSV disease. All three agents also demonstrate favourable and comparable tolerability profiles. Nirsevimab is now supported by a substantial body of real-world evidence confirming effectiveness in routine immunization programmes that closely align with registrational studies. Clesrovimab, as the newest agent, currently lacks real-world effectiveness, and both long-acting monoclonals require further confirmatory evidence in high-risk groups. Overall, existing data support that both monoclonals have equivalent efficacy and safety profiles as palivizumab, and choice should be based on cost-effectiveness and local availability, with consideration given to optimal integration of infant immunoprophylaxis alongside maternal RSV vaccination programmes. Full article
(This article belongs to the Special Issue Recent Progress of Vaccines for Respiratory Syncytial Virus (RSV))
11 pages, 222 KB  
Article
Prevalence and Antimicrobial Resistance of Pathogens Associated with Aerobic Vaginitis: A 10-Year Study in Greece
by Anthia Chasiakou, Stamatia Chasiakou, George Kaparos, Vasiliki-Georgia Prifti, Stiliani Demeridou, Athanasios Tsakris and Stavroula Baka
J. Clin. Med. 2026, 15(13), 4926; https://doi.org/10.3390/jcm15134926 (registering DOI) - 25 Jun 2026
Abstract
Background: Aerobic vaginitis (AV) is characterized by dysbiotic vaginal microflora with overgrowth of aerobic pathogens of enteric origin, presence of vaginal inflammation and immature epithelial cells. This study aimed to evaluate, over a period of 10 years, women of reproductive age (non-pregnant [...] Read more.
Background: Aerobic vaginitis (AV) is characterized by dysbiotic vaginal microflora with overgrowth of aerobic pathogens of enteric origin, presence of vaginal inflammation and immature epithelial cells. This study aimed to evaluate, over a period of 10 years, women of reproductive age (non-pregnant and pregnant) as well as menopausal women affected by AV. Methods: We included non-pregnant, pregnant and menopausal women diagnosed with AV over a period of 10 years. Diagnosis of AV was determined according to the criteria proposed by Donders in 2002. The isolated pathogens were identified with the rapid identification system I-dOne (Alifax S.r.l, Polverara, Italy) and the automated system VITEK2 (Biomerieux, Marcy l’Etoile, France), which was used for antimicrobial susceptibility testing. Results: The overall aerobic vaginitis prevalence rate during the studied period was 9.5%. The most common isolated pathogens were Escherichia coli 27.3%, Enterococcus faecalis 25.0%, Streptococcus agalactiae 22.2%, Klebsiella pneumoniae 8.9%, Proteus spp 4.7%, and Staphylococcus aureus 3.5%. E. coli infection significantly increased the odds of mild AV by 1.65 times (p = 0.002) and Proteus species infection was over 6 times more likely to progress to severe disease (p < 0.001). Furthermore, pregnant women were more likely to be infected with E. faecalis (p < 0.001) while menopausal women were diagnosed significantly more with severe AV (p < 0.001) compared to the other groups. Conclusions: The prevalence of aerobic vaginitis in the population studied was in concordance with global rates. Menopausal women displayed increased severe AV cases while, in contrast, mild cases were recorded during pregnancy. The most commonly isolated pathogens were of enteric origin. Full article
(This article belongs to the Special Issue Genitourinary Infections: Current Status and Emerging Challenges)
9 pages, 234 KB  
Case Report
Fulminant Hepatitis Due to Enterovirus E25 Systemic Infection in a Pediatric Patient
by Silvia Garattini, Lorenza Romani, Luana Coltella, Tommaso Alterio, Stefania Mercadante, Costanza Tripiciano, Maia De Luca, Sara Chiurchiù, Laura Cursi, Francesca Ippolita Calò Carducci, Cristina Russo, Carlo Federico Perno, Alberto Villani, Andrea Pietrobattista, Stefania Bernardi and Laura Lancella
Pathogens 2026, 15(7), 666; https://doi.org/10.3390/pathogens15070666 (registering DOI) - 25 Jun 2026
Abstract
Pediatric acute liver failure (PALF) is a rare but life-threatening condition characterized by rapid clinical deterioration and high mortality. Viral infections represent a major etiology of PALF, although the causative agent remains unidentified in a substantial proportion of cases. Human Enteroviruses (EVs) are [...] Read more.
Pediatric acute liver failure (PALF) is a rare but life-threatening condition characterized by rapid clinical deterioration and high mortality. Viral infections represent a major etiology of PALF, although the causative agent remains unidentified in a substantial proportion of cases. Human Enteroviruses (EVs) are typically associated with self-limiting illnesses; however, they may rarely cause severe systemic disease, including fulminant hepatitis, particularly in neonates and young children. We describe the case of a 4-year-old previously healthy male who presented with acute fulminant hepatitis secondary to systemic Echovirus 25 (E25) infection, with concomitant Epstein–Barr virus (EBV) co-infection of recent onset. The diagnosis was established through multiplex PCR on cerebrospinal fluid, blood, stool, and nasopharyngeal aspirate, with serotype confirmation by the Italian National Institute of Health. The patient required intensive supportive care including therapeutic plasma exchange (TPE), continuous kidney replacement therapy (CKRT), and intravenous immunoglobulins (IGIV). Despite initial clinical deterioration and placement on the liver transplant list, the patient achieved complete hepatic recovery and was discharged after fourteen days of hospitalization without requiring transplantation. This case highlights the importance of prompt virological workup including enterovirus PCR in children presenting with acute liver failure of undetermined etiology and supports the use of extracorporeal therapies as a bridge to recovery. Full article
(This article belongs to the Section Viral Pathogens)
15 pages, 572 KB  
Article
Impact of Gene Polymorphism rs2275913 and Serum IL-17A Levels on Liver Fibrosis Severity Across the Natural History of Chronic Hepatitis B in Indonesia
by Ummi Maimunah, Andrio Palayukan, Juniastuti, Brahmana Askandar Tjokroprawiro and Muhammad Miftahussurur
Diseases 2026, 14(7), 227; https://doi.org/10.3390/diseases14070227 (registering DOI) - 25 Jun 2026
Abstract
Background: A complex interplay between viral activity and host immune responses drives the progression of liver fibrosis in chronic hepatitis B. The T helper 17 (Th17) immune pathway, which produces the pro-inflammatory cytokine interleukin-17A (IL-17A), has been implicated in hepatic fibrogenesis. However, the [...] Read more.
Background: A complex interplay between viral activity and host immune responses drives the progression of liver fibrosis in chronic hepatitis B. The T helper 17 (Th17) immune pathway, which produces the pro-inflammatory cytokine interleukin-17A (IL-17A), has been implicated in hepatic fibrogenesis. However, the relationship between IL-17A levels, IL-17A G197A (rs2275913) gene SNP, and the degree of liver fibrosis across different phases of the natural history of chronic hepatitis B remains insufficiently explored. Methods: This study employed an analytical observational design with a cross-sectional approach in treatment-naïve patients with chronic hepatitis B. The degree of liver fibrosis was assessed using liver elastography. IL-17A (rs2275913) gene SNP was analysed using Real-Time PCR, while serum IL-17A levels were measured using enzyme-linked immunosorbent assay. Statistical analyses included Spearman’s correlation, the contingency coefficient, the Chi-square test, the Kruskal–Wallis test, and the Mann–Whitney test, with a significance level set at p < 0.05. Results: A total of 76 patients with chronic hepatitis B were included in this study. The phase of disease progression was significantly associated with the degree of liver fibrosis (p = 0.016). Median IL-17A levels increased in parallel with fibrosis severity (p = 0.003), with a particularly significant association observed during the R phase (p = 0.002). However, no significant association was found between the IL-17A G197A (rs2275913) gene SNP and either liver fibrosis severity or serum IL-17A levels. Conclusions: Elevated serum IL-17A levels were associated with greater liver fibrosis severity, particularly during the reactivation phase of chronic hepatitis B. These findings suggest a potential relationship between IL-17A-mediated immune responses and liver fibrosis in patients with chronic hepatitis B. Full article
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8 pages, 2970 KB  
Case Report
Improvement in Lower Facial Weakness and Swallowing Movements Following Semi-Dynamic Fascia Lata Grafting in Oculopharyngodistal Myopathy: A Case Report
by Sho Arakaki and Tetsuji Uemura
J. Aesthetic Med. 2026, 2(3), 12; https://doi.org/10.3390/jaestheticmed2030012 (registering DOI) - 25 Jun 2026
Abstract
Background: Oculopharyngodistal myopathy (OPDM) is a rare disorder with progressive ptosis, ophthalmoplegia, and oral incompetence, which pose challenges to management. While surgical interventions for blepharoptosis have been reported, addressing concurrent facial muscle weakness remains a significant challenge in comprehensive disease management. Case: A [...] Read more.
Background: Oculopharyngodistal myopathy (OPDM) is a rare disorder with progressive ptosis, ophthalmoplegia, and oral incompetence, which pose challenges to management. While surgical interventions for blepharoptosis have been reported, addressing concurrent facial muscle weakness remains a significant challenge in comprehensive disease management. Case: A 59-year-old woman with OPDM exhibited severe ptosis and oral incompetence. Despite undergoing prior cosmetic interventions, these symptoms had progressively worsened over 10 years. Preoperative evaluation revealed complete ptosis with a margin reflex distance 1 (MRD-1) of 0 mm and preserved Bell’s phenomenon. A two-stage reconstruction using fascia lata grafting corrected ptosis with a frontalis sling and restored oral competence with U-shaped grafts anchored to the zygomatic arches. Results: At 3 years and 6 months postoperatively, eyelid elevation had improved without corneal exposure, and oral competence was restored, resolving drooling. Conclusions: Semi-dynamic reconstruction using fascia lata grafting effectively addresses ptosis and oral incompetence in OPDM, improving visual and swallowing functions and enhancing quality of life. Full article
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19 pages, 741 KB  
Article
Enhanced Discrimination of Coronary Artery Disease Severity by Circulating Phoenixin-14: Evidence from a Clinical Laboratory Study
by İsmail Polat, Bekir Dagdeviren, Mehdi Karasu, Ömer Bedir, Suna Aydin, Elif Emre, Musa Sari, Özlem Seçen, Çetin Mirzaoglu and Suleyman Aydin
Int. J. Mol. Sci. 2026, 27(13), 5719; https://doi.org/10.3390/ijms27135719 (registering DOI) - 24 Jun 2026
Abstract
Early identification of anatomically significant coronary artery disease (CAD) remains a major clinical challenge despite advances in cardiovascular diagnostics. Novel circulating biomarkers may improve risk stratification and diagnostic discrimination beyond conventional parameters. We investigated the diagnostic utility of four emerging biomarkers—Phoenixin-14, Syntenin-1, Alamandine, [...] Read more.
Early identification of anatomically significant coronary artery disease (CAD) remains a major clinical challenge despite advances in cardiovascular diagnostics. Novel circulating biomarkers may improve risk stratification and diagnostic discrimination beyond conventional parameters. We investigated the diagnostic utility of four emerging biomarkers—Phoenixin-14, Syntenin-1, Alamandine, and Cerebellin-1—for the assessment of CAD severity. In this prospective observational study, 90 participants undergoing coronary angiography were categorized into three groups: severe CAD (≥70% stenosis; n = 30), non-obstructive/non-critical CAD (<70% stenosis; n = 30), and angiographically normal controls (n = 30). Patients with acute coronary syndrome, diabetes mellitus, prior coronary revascularization, cardiomyopathy, or significant systemic disease were excluded. Circulating biomarker concentrations were quantified using the enzyme-linked immunosorbent assay. Comparative analyses, correlation testing, and receiver operating characteristic (ROC) analyses were performed to evaluate discriminatory performance. Circulating Phoenixin-14 concentrations progressively declined across the control, non-critical CAD, and severe CAD groups [40.1 (29.0–49.7) vs. 24.4 (18.5–30.1) vs. 16.7 (13.4–19.0) pg/mL, respectively; p < 0.001]. Phoenixin-14 demonstrated outstanding discrimination for severe CAD, achieving an area under the ROC curve (AUC) of 0.969 (95% CI, 0.888–0.997), with 86.7% sensitivity and 96.7% specificity at a threshold of ≤20.2 pg/mL. Diagnostic performance was substantially lower for Syntenin-1 (AUC, 0.795), Alamandine (AUC, 0.661), and Cerebellin-1 (AUC, 0.597). Phoenixin-14 also showed robust discrimination for non-critical CAD (AUC, 0.832). Biomarker concentrations exhibited correlations with metabolic indices while remaining largely independent of traditional cardiovascular risk factors. Among the evaluated novel circulating biomarkers, Phoenixin-14 demonstrated superior diagnostic performance for both obstructive and non-obstructive CAD, markedly outperforming Syntenin-1, Alamandine, and Cerebellin-1. These findings identify Phoenixin-14 as a promising candidate biomarker for CAD severity assessment and clinical risk stratification. Larger multicenter studies are warranted to validate these exploratory findings and determine their incremental value in contemporary cardiovascular practice. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
12 pages, 843 KB  
Review
The Role of FGF1 in Chronic Liver Diseases
by Tao Liu, Meihong Yu, Liu Han, Jing Wu, Deliang Liu and Yuyong Tan
Biomedicines 2026, 14(7), 1436; https://doi.org/10.3390/biomedicines14071436 (registering DOI) - 24 Jun 2026
Abstract
Chronic liver disease (CLD) constitutes a major global health burden, with high morbidity and mortality, limited treatment options for several etiologies, and an urgent need for novel therapeutic targets. Fibroblast growth factor 1 (FGF1) is a unique member of the FGF family capable [...] Read more.
Chronic liver disease (CLD) constitutes a major global health burden, with high morbidity and mortality, limited treatment options for several etiologies, and an urgent need for novel therapeutic targets. Fibroblast growth factor 1 (FGF1) is a unique member of the FGF family capable of binding all four FGFR subtypes, thereby regulating multiple signaling pathways including PI3K/AKT, Ras/MAPK, and PLCγ, which are involved in metabolism, cell survival, proliferation, and tissue repair. Emerging evidence highlights the multifaceted and context-dependent roles of FGF1 in CLD. In drug-induced liver injury (DILI) caused by anti-tuberculosis drugs, acetaminophen, or doxorubicin, FGF1 confers protection by restoring bile acid homeostasis, reducing oxidative stress, inflammation, and apoptosis. In Metabolic dysfunction-associated steatotic liver disease (MASLD), FGF1 ameliorates hepatic steatosis, oxidative injury, and insulin resistance through downregulation of SREBP1, upregulation of PPARα, and activation of Nrf2-mediated antioxidant responses. Conversely, in primary sclerosing cholangitis (PSC), FGF1 aggravates ductular reaction, biliary senescence, and liver fibrosis via upregulation of SASP and TGF-β1, suggesting that inhibition of the FGF1/FGFR axis may be therapeutic. For alcohol-related liver disease (ALD), although direct experimental evidence is lacking, FGF1 is hypothesized to confer protection given its known activities against oxidative stress, lipid dysregulation, and cell death. Despite its promise, the mitogenic potential of FGF1 raises safety concerns; however, N-terminally modified FGF1 analogs (e.g., FGF1Δ) retain metabolic benefits with reduced proliferative activity. Collectively, FGF1 represents a versatile and disease-dependent regulator in CLD, warranting further mechanistic studies, safety evaluations, and development of targeted analogs as a novel therapeutic strategy for difficult-to-treat liver diseases. Full article
(This article belongs to the Special Issue Chronic Liver Disease: From Mechanisms to Therapeutic Approaches)
25 pages, 1038 KB  
Systematic Review
The Latest Advances in Rosacea Treatment: A Systematic Review
by Anastazja Andrusiewicz, Sofiia Khimuk, Jakub Niżnik, Dmytro Sirko, Daniel Mijas and Danuta Nowicka
Pharmaceuticals 2026, 19(7), 982; https://doi.org/10.3390/ph19070982 (registering DOI) - 24 Jun 2026
Abstract
Background: Rosacea is a chronic inflammatory dermatosis characterized by vascular dysregulation, immune dysfunction, neurovascular alterations, and microbial involvement. Recent advances in understanding its pathophysiology have led to the development of targeted therapeutic strategies addressing multiple disease mechanisms. This systematic review aimed to evaluate [...] Read more.
Background: Rosacea is a chronic inflammatory dermatosis characterized by vascular dysregulation, immune dysfunction, neurovascular alterations, and microbial involvement. Recent advances in understanding its pathophysiology have led to the development of targeted therapeutic strategies addressing multiple disease mechanisms. This systematic review aimed to evaluate contemporary evidence regarding emerging and established treatment approaches for rosacea. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, and Web of Science were searched for studies published between 2016 and 2025. Original human studies evaluating therapeutic interventions for rosacea were included. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. Results: Fifteen studies involving 537 patients with rosacea and 77 controls (614 participants in total) met the eligibility criteria. Evaluated interventions included vascular-targeted therapies, topical anti-inflammatory agents, systemic and immunomodulatory treatments, and microbiome-oriented approaches. Oxymetazoline, pulsed-dye laser, platelet-rich plasma, ivermectin, azelaic acid, dapsone, sulfur preparations, and metronidazole demonstrated clinical benefits in reducing erythema, inflammatory lesions, or overall disease severity. Emerging therapies, including tofacitinib and oral ivermectin, showed promising results in refractory disease. Microbiome-related interventions, particularly Demodex-targeted therapies and Helicobacter pylori eradication, were also associated with clinical improvement. Risk-of-bias assessment identified two studies with low risk of bias, twelve with moderate risk of bias, and one study with high risk of bias. Conclusions: Current evidence supports a multimodal and mechanism-based approach to rosacea management, integrating vascular, inflammatory, immunological, and microbiological targets. However, the available evidence remains limited by small sample sizes, heterogeneous methodologies, short follow-up periods, and a predominance of non-randomized study designs. Large, well-designed randomized controlled trials are needed to establish optimal evidence-based treatment strategies and define the long-term efficacy and safety of emerging therapies. Full article
(This article belongs to the Special Issue Drug Therapy for Autoimmune and Inflammatory Skin Conditions)
23 pages, 757 KB  
Review
Biosecurity and Diagnosis of Viral Hemorrhagic Fevers: Strategic Considerations for Military Medicine
by Salvatore Giovanni De-Simone, Andreia Carneiro da Silva, Marianne Melo Monnerat, Carlos Medicis Morel, David William Provance and Flávio Rocha da Silva
Diagnostics 2026, 16(13), 1968; https://doi.org/10.3390/diagnostics16131968 (registering DOI) - 24 Jun 2026
Abstract
Viral hemorrhagic fevers (VHFs) are severe infectious diseases caused by RNA viruses of the families Arenaviridae, Filoviridae, Flaviviridae, and Hantaviridae, characterized by high morbidity, significant case fatality rates, and frequent diagnostic uncertainty in early disease stages. For military medical services, timely clinical recognition [...] Read more.
Viral hemorrhagic fevers (VHFs) are severe infectious diseases caused by RNA viruses of the families Arenaviridae, Filoviridae, Flaviviridae, and Hantaviridae, characterized by high morbidity, significant case fatality rates, and frequent diagnostic uncertainty in early disease stages. For military medical services, timely clinical recognition and laboratory confirmation are essential to guide patient management, prevent nosocomial transmission, and maintain operational continuity, particularly in endemic or resource-limited deployment settings. This review critically examines current diagnostic approaches to VHF-causative agents, emphasizing their use in clinical and field medical settings. The diagnostic process, from exposure through specimen collection, laboratory testing, and result interpretation is analyzed, including the use of molecular, serological, and antigen-based assays. Particular attention is given to deployable diagnostic platforms and their role in bridging the gap between frontline clinical suspicion and definitive laboratory confirmation. Biosafety requirements and infection prevention measures are discussed as integral components of clinical diagnostic workflows, aligned with guidance from the World Health Organization and the Centers for Disease Control and Prevention. Comparative analyses of virus-specific diagnostic timelines and laboratory requirements are presented to support differential diagnosis and clinical decision-making. Emerging technologies, including rapid molecular assays and genomic methods, are evaluated for their potential to improve early diagnosis and patient outcomes. This review highlights the central role of diagnostic readiness in clinical management of the VHFs and provides evidence-based considerations to support military clinicians facing high-risk febrile illnesses in operational environments. Full article
(This article belongs to the Collection Diagnostic Virology)
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15 pages, 1022 KB  
Article
P. hybridus Extract Ze 339 Inhibits RSV Infection by Altering Host Metabolism
by Fabian Otte, Verena M. Merk, Georg Boonen, Thomas Klimkait, Veronika Butterweck and David Hauser
Viruses 2026, 18(7), 697; https://doi.org/10.3390/v18070697 (registering DOI) - 24 Jun 2026
Abstract
Respiratory syncytial virus (RSV) remains a major cause of severe respiratory disease worldwide, particularly affecting young children and immunocompromised individuals, highlighting the need for additional therapeutic strategies. In this study, the antiviral activity of the Petasites hybridus extract Ze 339 was investigated in [...] Read more.
Respiratory syncytial virus (RSV) remains a major cause of severe respiratory disease worldwide, particularly affecting young children and immunocompromised individuals, highlighting the need for additional therapeutic strategies. In this study, the antiviral activity of the Petasites hybridus extract Ze 339 was investigated in RSV-infected cell-culture models. Antiviral efficacy was assessed using plaque reduction assays, reporter virus analyses, and proteomic profiling to elucidate potential mechanisms of action. Ze 339 potently reduced the infectivity of both RSVA and RSVB in vitro and retained antiviral activity when administered up to six hours post-infection, resulting in markedly reduced plaque formation and viral protein biosynthesis without inducing cytotoxicity. Proteomic analyses revealed that Ze 339 modulates host cell pathways associated with reduced cell proliferation, attenuated immune signaling, and enhanced cholesterol and lipid metabolism. These changes were more pronounced in infected than in uninfected cells and coincided with a marked downregulation of viral proteins. The observed proteomic signature suggests a host-directed antiviral effect and identifies altered lipid metabolism and cell-cycle-associated pathways as potential contributors to reduced RSV replication. Taken together, these findings demonstrate the antiviral activity of Ze 339 against RSV and support the hypothesis that modulation of host cell pathways contributes to its antiviral effects, providing a rationale for further evaluation of Ze 339 as a repurposed therapeutic candidate for RSV infection. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
22 pages, 1994 KB  
Article
Naphthoquinone-Amino Acids Regulate Cellular Cancer Associated Processes, p53 and miR-34a-5p Expression in Immortal and Tumorigenic Cervical Cell Lines
by Jessica Lizbeth Sifuentes-Padilla, Angelica Judith Granados-López, Antonia Monserrat Campos-Lujan, Abel Suárez-Castro, Mayra Denise Herrera, Yamilé López-Hernández, Hiram Hernández-López, José Antonio Varela-Silva, Rosalinda Gutiérrez-Hernández, Claudia Araceli Reyes-Estrada, Sergio Hugo Sánchez-Rodríguez, Ernesto Rivera-Ávalos, Denisse de Loera and Jesús Adrián López
Int. J. Mol. Sci. 2026, 27(13), 5703; https://doi.org/10.3390/ijms27135703 (registering DOI) - 24 Jun 2026
Abstract
Cervical cancer is a malignant disease that affects women worldwide and is associated with both high incidence and a high mortality rate. miR-34 is a direct transcriptional-target of p53 and is downregulated in several types of cancers. 1,4-Naphthoquinones (NQs) have anticancer properties and [...] Read more.
Cervical cancer is a malignant disease that affects women worldwide and is associated with both high incidence and a high mortality rate. miR-34 is a direct transcriptional-target of p53 and is downregulated in several types of cancers. 1,4-Naphthoquinones (NQs) have anticancer properties and have been used to modulate miR-34 expression. We tested (3-chloro-NQ-2-yl)-alanine (ANQCl), -methionine (MNQCl), -glycine (GNQCl), -phenylalanine (FNQCl), -asparagine (NNQCl), and (1,4-napthoquinon-2-yl)-asparagine (NNQ) in immortal and tumorigenic cells, both HPV-positive and -negative, simulating precancerous and cancerous status to observe the response of the p53-miR-34 system, migration and invasion. A dose–response was achieved to determine the IC50 of the compounds in SiHa, CaLo, C33-A and HaCaT cells. HaCaT cell migration inhibition was more potent than in SiHa, CaLo, and C33-A cells, while invasion hindrance was more evident in the tumorigenic SiHa, CaLo and C33-A. NNQCl, GNQCl, ANQCl and FNQCl compounds induced p53 overexpression in SiHa and CaLo cells. Compound ANQCl in SiHa and FNQCl in CaLo induced miR-34a overexpression, probably via p53. Migration and invasion of most compounds decreased independently of p53-miR-34. NQ-amino acids exert effect on cell proliferation, migration and invasion in cervical cancer cells, suggesting their potential use in the field of cancer treatment. Full article
(This article belongs to the Special Issue Recent Advances in Non-Coding RNAs in Human Research)
16 pages, 720 KB  
Article
Prevalence of rs850683722 Variant and Its Influence on the Course of Myxomatous Mitral Valve Disease in 105 Cavalier King Charles Spaniel Dogs in the Polish Population
by Maksymilian Lewicki, Sylwia Barbara Górczyńska-Kosiorz, Justyn Gach, Piotr Frydrychowski, Zuzanna Wojtczak and Agnieszka Noszczyk-Nowak
Animals 2026, 16(13), 1956; https://doi.org/10.3390/ani16131956 (registering DOI) - 24 Jun 2026
Abstract
Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disease in small-breed dogs and shows particularly high prevalence and early onset in Cavalier King Charles Spaniels (CKCS). Although MMVD is considered a complex, polygenic disease, the clinical relevance of individual genetic [...] Read more.
Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disease in small-breed dogs and shows particularly high prevalence and early onset in Cavalier King Charles Spaniels (CKCS). Although MMVD is considered a complex, polygenic disease, the clinical relevance of individual genetic variants remains incompletely understood. The angiotensin-converting enzyme (ACE) gene variant rs850683722 has previously been associated with altered ACE activity and differences in renin–angiotensin–aldosterone system-related responses in dogs with MMVD. The aim of this study was to determine the prevalence of rs850683722 in a Polish population of CKCS dogs and to assess whether this variant is associated with the clinical course of MMVD. A total of 105 CKCS dogs were included in the study. All dogs underwent standardized cardiovascular evaluation, including echocardiography, electrocardiography, and systolic blood pressure measurement. MMVD diagnosis and staging were performed according to current ACVIM consensus criteria. Genotyping of the rs850683722 variant was performed using Sanger sequencing for 95 dogs, while next-generation sequencing data was obtained for 10 dogs. Genotype distribution, allele frequencies, conformity with the Hardy–Weinberg equilibrium (HWE), sex-related differences, and associations between genotype and age at progression to selected MMVD stages or the primary clinical endpoint were assessed statistically. The most frequent genotype was AA, detected in fifty-nine dogs, followed by GG in thirty-seven dogs and AG in nine dogs. When dogs carrying at least one A allele were considered variant-positive, the overall prevalence of the variant-positive genotype was 64.8%. The calculated allele frequencies were 0.605 for the A allele and 0.395 for the G allele. The observed genotype distribution deviated markedly from the Hardy–Weinberg equilibrium, mainly because of a pronounced deficit of heterozygous dogs. No significant association was detected between genotype and sex. Genotype was also not significantly associated with age at progression to stage B2 or stage C. A statistically significant difference in age of death was demonstrated by genotype, but this difference was not reflected in the survival analysis. The rs850683722 variant was highly prevalent in the studied Polish CKCS population, with a frequency comparable to previously reported data for this breed. Despite its documented biological association with ACE activity and RAAS-related responses, the variant was not significantly associated with the clinical progression of MMVD in this cohort. These findings suggest that rs850683722 alone seems unlikely to be a reliable marker for predicting the severity or rate of MMVD progression in Polish CKCS dogs. Further studies including larger cohorts, longer follow-up, pedigree information, and the direct assessment of RAAS activity may help clarify whether this variant has stage-dependent or treatment-related clinical relevance. Full article
(This article belongs to the Section Veterinary Clinical Studies)
9 pages, 4623 KB  
Case Report
Multiple Brain Microabscesses and a Lung Abscess Caused by Streptococcus intermedius Following COVID-19: A Case Report and Literature Review
by Ryoma Takeda, Kazunori Yamada, Takenori Abe, Tomoyuki Ishigo and Hirohiko Nakamura
Infect. Dis. Rep. 2026, 18(4), 64; https://doi.org/10.3390/idr18040064 (registering DOI) - 24 Jun 2026
Abstract
Background: Secondary bacterial infections are increasingly recognized after coronavirus disease 2019 (COVID-19); however, bacterial abscess formation remains uncommon, and the simultaneous occurrence of brain and lung abscesses has not been previously reported. We report a rare case of Streptococcus intermedius infection presenting with [...] Read more.
Background: Secondary bacterial infections are increasingly recognized after coronavirus disease 2019 (COVID-19); however, bacterial abscess formation remains uncommon, and the simultaneous occurrence of brain and lung abscesses has not been previously reported. We report a rare case of Streptococcus intermedius infection presenting with multiple brain microabscesses and a lung abscess following COVID-19. Case Presentation: A 75-year-old man with no significant medical history except cholelithiasis experienced persistent fever following a diagnosis of COVID-19 and subsequently developed impaired consciousness 17 days later. Because bacterial meningitis was suspected, he was admitted to a neurology-specialized hospital on the same day. Brain MRI revealed more than 80 small enhancing lesions scattered throughout the brain parenchyma, consistent with multiple microabscesses. Chest CT demonstrated a mass-like lesion in the left lower lobe. Although cerebrospinal fluid cultures were negative, blood cultures obtained on admission yielded S. intermedius. Further investigation of the source of infection revealed moderate periodontitis, suggesting the oral cavity as the probable portal of entry. The patient was treated with intravenous antibiotics for eight weeks based on antimicrobial susceptibility testing, resulting in near-complete resolution of the lesions. Conclusions: Although a causal relationship between COVID-19 and abscess formation cannot be established, COVID-19-associated immune and mucosal barrier dysfunction may have contributed to the progression and dissemination of infection in this patient. Clinicians should be aware of the possibility of severe bacterial superinfection when fever or respiratory symptoms related to COVID-19 persist, even in patients without overt immunocompromise, particularly in those with pre-existing oral infections. Full article
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