Search Results (2,812)

Background: Compressive cryotherapy, which combines cold therapy with compression, has gained attention to relieve pain and swelling after the Knee arthroscopy. However, there is still limited evidence specifically related to its use after knee arthroscopy. Objective: This study investigated the efficacy of compressive cryotherapy in decreasing postoperative pain and swelling in patients following knee arthroscopy. Methods: A quasi-experimental study was conducted at the Kasr Al-Ainy Hospital. Sixty patients scheduled for knee arthroscopy were divided into two groups. The intervention group (n = 30) received compressive cryotherapy using a cold-pack knee wrap set at 2 to 5 °C for 15 to 20 min, three times daily. The control group (n = 30) received standard postoperative care. Pain was assessed with the Numerical Rating Scale. Swelling was measured by assessing knee circumference at the mid-patella. Assessments occurred immediately after surgery (baseline), and on the first and second postoperative days. Non-parametric tests used in the analysis included the Chi-square test, the Mann–Whitney U test, the Friedman test, and the Wilcoxon signed-rank test with Bonferroni–Holm correction. Results: Patients in the compressive cryotherapy group experienced a greater reduction in pain than those in the control group. By the first postoperative day, none of the patients in the intervention group reported severe pain (p < 0.001). Knee circumference decreased significantly in the intervention group, from a median of 51.05 cm [IQR: 49.1–53.2] at baseline to 40.90 cm [39.8–42.1] by the second day. In comparison, the control group showed a smaller reduction, from 52.70 cm [50.8–54.5] to 48.55 cm [46.8–50.9]. Between-group differences in swelling were significant at the first postoperative assessment (U = 105.0, p < 0.001) and on day 2 (U = 62.5, p < 0.001). Overall, differences in both pain intensity and knee swelling between groups were statistically significant across all time points (p < 0.001). Conclusions: Compressive cryotherapy is an effective non-pharmacological intervention for reducing pain and swelling in the early postoperative period following knee arthroscopy. These results suggest that it could be a valuable addition to routine postoperative care, helping patients recover more comfortably and quickly. Full article

Background: Heart re-transplantation represents an effective option in selected patients with graft failure. Although the results of heart re-transplantation have improved in recent years, little is known about the outcomes in patients requiring late (>1 year) re-transplantation or about the effects of prolonged exposure to immunosuppression on multiorgan function. Methods: Among all the heart re-transplantations performed, from November 1988 to April 2025, a total of 30 patients underwent late re-transplantation. Since literature data on late re-HTx are generally limited to those performed within 20 years, patients were divided according to the interval from primary to re-transplantation: <20 (Group A) or ≥20 years (Group B). Results: Group A included 17 patients re-transplanted after a median time of 15 years, and Group B 13 patients after a median time of 23 years. Group B patients were more commonly affected by severe chronic kidney disease and received more combined heart and kidney transplantation. Overall survival at 1, 5 and 10 years was 80%, 68% and 60%, and did not differ between Groups A and B (p = 0.5). However, Group B recipients were more commonly affected by malignancies (p < 0.01). Compared to primary heart transplantation in the same population, re-transplantation was associated with higher, albeit not statistically significantly, rates of infections, grade ≥ 2 rejections and malignancies. Conclusions: Late heart re-transplantation is associated with satisfactory outcomes and could be effectively considered in patients with late graft dysfunction. However, the prolonged exposure to immunosuppression requires particular attention in early pharmacological management as well as a close follow-up, especially in patients requiring heart re-transplantation after >20 years. Full article

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy caused by persistent infection with human T-cell leukemia virus type 1 (HTLV-1). ATLL remains difficult to treat despite intensive chemotherapy, antiviral therapy, and hematopoietic stem cell transplantation. The limited durability of current treatment strategies highlights the need for mechanism-based therapeutic approaches. Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that regulates transcription, RNA splicing, DNA damage responses, and immune signaling through symmetric dimethylation of histone and non-histone substrates. PRMT5 is frequently overexpressed across hematologic and solid tumors. Preclinical studies indicate that PRMT5 expression is elevated during HTLV-1-mediated T-cell transformation and that pharmacologic inhibition of PRMT5 selectively impairs the survival and transformation of infected T cells in vitro and in vivo. In this review, we highlight the current understanding of PRMT5 biology in cancer, summarize preclinical studies supporting PRMT5 as a therapeutic target in ATLL, and discuss key challenges to future clinical translation. We also discuss emerging approaches such as rational combination therapies and tumor-selective PRMT5 inhibitors as potential paths toward treatment for ATLL. Full article

While drug-eluting cardiovascular devices, including drug-eluting stents and drug-coated balloons, have significantly reduced restenosis rates, they remain limited by delayed vascular healing, chronic inflammation, and late adverse events. These limitations reflect a fundamental mismatch between current device pharmacology, which relies on nonselective antiproliferative drugs, and the highly coordinated, cell-specific programs that orchestrate vascular repair. Extracellular vesicles (EVs), nanometer-scale membrane-bound particles secreted by virtually all cell types, provide a biologically evolved platform for intercellular communication and cargo delivery. In the cardiovascular system, EVs regulate endothelial regeneration, smooth muscle cell phenotype, extracellular matrix remodeling, and macrophage polarization through precisely orchestrated combinations of miRNA, proteins, and lipids. Here, we synthesize mechanistic insights into EV biogenesis, cargo selection, recruitment, and functional effects in vascular healing and inflammation and translate these into a formal framework for EV-inspired device engineering. We discuss how EV-based or EV-mimetic coatings can be designed to sense the local microenvironment, deliver encoded biological “instruction sets,” and function within ECM-mimetic scaffolds to couple local stent healing with systemic tissue repair. Finally, we outline the manufacturing, regulatory, and clinical trial issues that must be addressed for EV-inspired cardiovascular devices to transition from proof of concept to clinical reality. By shifting the focus from pharmacological suppression to biological regulation of healing, EV-based strategies offer a path to resolve the long-standing tradeoff between restenosis prevention and durable vascular healing. Full article

Motor disorders are increasingly recognized as a significant complication of chronic kidney disease (CKD), yet they remain underdiagnosed, undertreated, and often overlooked in clinical practice. Patients with CKD experience a broad spectrum of motor disturbances, including restless legs syndrome, myoclonus, flapping tremor, periodic limb movements in sleep, Parkinsonism, and peripheral neuropathy. These disorders arise from complex and often overlapping mechanisms such as uremic neurotoxicity, vascular injury, electrolyte and hormonal imbalances, or inflammatory processes, reflecting the systemic impact of impaired renal function on the central and peripheral nervous systems. The presence of motor disorders in CKD is associated with substantial clinical consequences for quality of life, contributing to impaired mobility, persistent insomnia, daytime fatigue, higher fall risk, and diminished independence. Moreover, these disturbances have been linked to increased cardiovascular morbidity and mortality, further exacerbating the already high burden of disease in this population. Current management approaches focus on optimizing kidney function through dialysis or transplantation, pharmacological therapies such as dopaminergic agents, gabapentinoids, and iron supplementation, as well as non-pharmacological interventions including structured exercise programs and sleep hygiene measures. Despite these strategies, robust evidence on long-term outcomes, comparative effectiveness, and optimal treatment algorithms remains limited. Greater recognition of the clinical impact of motor disorders in CKD, combined with targeted research efforts, is urgently needed to improve patient-centered outcomes and guide evidence-based care. Full article

Background/Objectives: The first 1000 days of life represent a critical window for growth and neurodevelopment, during which nutrition strongly influences brain development and metabolic programming. In phenylketonuria (PKU), dietary management is essential to prevent neurological impairment and later-life risk of non-communicable diseases (NCDs). This review examines current evidence on PKU from pregnancy through complementary feeding, highlighting the impact of nutritional strategies on neurodevelopmental and metabolic outcomes. Methods: This narrative review, following PRISMA guidelines, used a systematic search of PubMed and Scopus with defined PICO questions. Original research, reviews, and guidelines on PKU nutrition during the first 1000 days were included, emphasizing neurological and metabolic outcomes. Results: Articles addressed prenatal and postnatal factors in PKU. Optimised metabolic control in women with PKU is critical to prevent maternal PKU syndrome, reducing risks of miscarriage, congenital heart defects, microcephaly, and neurocognitive impairment. Pre-conception dietary management, frequent blood Phe monitoring, supplementation with Phe-free protein substitutes (PSs), micronutrients, and emerging pharmacological therapies support maternal and foetal health. Following newborn screening, early dietary treatment in infants with PKU maintains plasma Phe within safe ranges, promoting growth and neurodevelopment. Breastfeeding, combined with Phe-free infant PSs, is feasible, and complementary feeding should be introduced carefully. Frequent monitoring and tailored dietary adjustments, including second-stage PSs, support metabolic control, while data on gut microbiota remain limited. Conclusions: Early multidisciplinary interventions are crucial to optimise metabolic and neurodevelopmental outcomes during this window of opportunity. Further research is needed to address remaining gaps and optimise PKU management across the first 1000 days. Full article

Organoids are three-dimensional multicellular structures that mimic key aspects of native tissues consisting ideal tools to study organ development and pathophysiology when incorporated in customized bioscaffolds. In vivo, the extracellular matrix (ECM) maintains tissue integrity and regulates cell adhesion, migration, differentiation, and survival through biochemical and mechanical signals. Tissue-derived decellularized extracellular matrix (dECM) can preserve organ-specific biochemical signals and cell-adhesive motifs, creating a bioactive environment that supports physiologically relevant organoid growth. 3D bioprinting technology marks a transformative phase in organoid research by enhancing the structural and functional complexity of organoid models and expanding their application in pharmacology and regenerative medicine. These systems enhance tissue modeling and drug testing while adhering to the principles of animal replacement, reduction, and refining (3Rs) in research. Remaining challenges include donor variability, limited mechanical stability, and the lack of standardized decellularization protocols that can be addressed by adopting quality and safety metrics. The combination of dECM-based biomaterials and 3D bioprinting holds great potential for the development of human-relevant, customizable, and ethically sound in vitro models for regenerative medicine and personalized therapies. In this review, we discuss the latest (2021–2025) developments in applying extracellular matrix bioprinting techniques to organoid technology, presenting examples for the most commonly referenced organoid types. Full article

Background: Submacular hemorrhage (SMH) is a vision-threatening condition most associated with neovascular age-related macular degeneration (nAMD), although it may also arise from polypoidal choroidal vasculopathy, pathological myopia, retinal vascular diseases, trauma, and systemic factors. Rapid management is essential because subretinal blood induces photoreceptor toxicity, clot organization, and fibroglial scarring, leading to irreversible visual loss. The choice and urgency of treatment depend on hemorrhage size, duration, and underlying pathology, and the patient’s surgical risk category, which can influence the invasiveness of the selected procedure. This review aims to provide an updated synthesis of recent advances in the surgical and pharmacological management of SMH, focusing on evidence from the past five years and comparing outcomes across major interventional approaches. Methods: A narrative review of 27 recent clinical and multicentre studies was conducted. The included literature evaluated pneumatic displacement (PD), pars plana vitrectomy (PPV), subretinal or intravitreal recombinant tissue plasminogen activator (rtPA), anti-VEGF therapy, and hybrid techniques. Studies were analyzed about indications, surgical methods, timing of intervention, anatomical and functional outcomes, and complication and patient risk stratification. Results: Outcomes varied depending on the size and duration of hemorrhage, as well as the activity of underlying macular neovascularization. PD with intravitreal rtPA was reported as effective for small and recent SMH. PPV combined with subretinal rtPA, filtered air, and anti-VEGF therapy demonstrated favorable displacement and visual outcomes in medium to large hemorrhages or those associated with active nAMD. Hybrid techniques further improved clot mobilization in selected cases. Across studies, delayed intervention beyond 14 days correlated with reduced visual recovery due to blood organization and photoreceptor loss. Potential risks, including recurrent bleeding and rtPA-associated toxicity, were reported but varied across studies. Conclusions: Management should be individualized, considering hemorrhage characteristics and surgical risk. Laser therapy, including PDT, may serve as an adjunct in the perioperative or postoperative period, particularly in PCV patients. Early, tailored intervention typically yields the best functional outcomes. Full article

Cervical cancer (CC) remains a common malignant tumor that seriously threatens women’s health globally. Gramine (GR), a natural alkaloid derived from plants such as Arundo donax L., exhibits anti-tumor activities, yet its mechanistic actions in CC are still unclear. Here, we integrated cell-based assays, network pharmacology, and multi-omics analysis to systematically investigate the molecular mechanisms underlying GR’s anti-CC effects. In vitro experiments showed that GR significantly inhibited proliferation and migration, induced apoptosis, and triggered G₀/G₁ phase cell cycle arrest in HeLa cells. Integrated multi-omics analysis identified CDK2 as a critical target of GR, with both mRNA and protein levels markedly reduced following treatment. Mechanistically, GR likely suppresses CC progression by modulating the “CYP4A22-AS1/LINC00958–hsa-miR-133b–CDK2” competitive endogenous RNA (ceRNA) axis. Immune analysis indicated positive correlations of CDK2, CYP4A22-AS1, and LINC00958 with the immune checkpoint molecule CD47. Collectively, our findings demonstrate that GR inhibits CC through a ncRNA-mediated suppression of CDK2, leading to reduced HeLa cell proliferation and migration and enhanced apoptosis. These results provide a mechanistic rationale for developing GR as a candidate agent for targeted therapy and immuno-combination strategies in CC. Full article

Background: Facial palsy constitutes a profoundly disabling condition, often leading to marked functional deficits and a decline in facial appearance, which substantially reduces the patient’s quality of life. A combined therapy of botulinum toxin (BoNTA), hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) appears promising in the pharmacological approach of these patients. Methods: We reported our single center experience of patients with facial palsy, either of central or peripheral etiology who were treated with the combination of BoNTA, HA and CaHA, during a 6-month period (January 2025–June 2025). Results: Eight consecutive adult patients [mean age: 49.50 ± 7.95 years, 6 (75%) female] with facial palsy, either of central (4 patients) or peripheral (4 patients) etiology, received the combination of BoNTA, HA and CaHA. No serious adverse reactions were documented. Localized bruising and swelling at injection sites resolved without requiring any additional intervention. Facial Disability Index (FDI) was assessed both prior to and following treatment. The functional subscale increased from 65.63 ± 16.13 to 80.63 ± 10.50 (improvement rate = 24.4%, p-value = 0.002), while the psychosocial subscale increased from 63.00 ± 17.34 to 74.50 ± 10.89 (improvement rate = 18.3%, p-value = 0.004). Consequently, the total FDI score improved from 128.63 ± 28.92 to 155.13 ± 17.96 (overall improvement = 20.6%, p-value = 0.001). Conclusions: The present case series underscores the potential therapeutic role of CaHA as an adjunct to BoNTA and HA injections in patients with central or peripheral facial palsy. Full article

Background: Preterm birth, affecting more than 13.4 million infants worldwide each year, remains one of the leading causes of neonatal morbidity and mortality. Among its complications, respiratory distress syndrome and bronchopulmonary dysplasia are predominant contributors to prolonged hospitalization and respiratory support needs. As advances in perinatal care have improved survival, attention has increasingly turned to optimizing respiratory function and reducing complications through non-pharmacological interventions. Respiratory physiotherapy has therefore gained recognition as a valuable adjunct to medical management in this population. Purpose: To provide a comprehensive synthesis of the current clinical evidence regarding respiratory physiotherapy techniques used in preterm neonates with respiratory distress syndrome or bronchopulmonary dysplasia. Summary of Evidence: The available literature describes several physiotherapeutic modalities—including prolonged slow expiration, postural treatment, Vöjta therapy, and gentle mechanical techniques—aimed at improving ventilation, gas exchange, and secretion clearance. Across diverse studies, these interventions have been associated with better oxygenation, improved heart and respiratory rates, shorter mechanical ventilation time, and reduced hospital stay, while showing no relevant adverse effects. Although methodological heterogeneity persists, the consistency of beneficial trends supports their integration into multidisciplinary neonatal care. Conclusions: Respiratory physiotherapy represents a safe and promising therapeutic complement for preterm neonates with respiratory distress syndrome or bronchopulmonary dysplasia. Techniques that combine postural control and controlled expiratory maneuvers appear particularly effective in enhancing pulmonary mechanics and recovery. Future research should focus on standardizing intervention protocols, identifying optimal timing and dosing, and evaluating the long-term respiratory and developmental outcomes of these physiotherapeutic strategies. Full article

Feline coronaviruses (FCoVs) are ubiquitous pathogens, exhibiting high prevalence across feline populations worldwide. Although the virulent mutated biotype feline infectious peritonitis virus (FIPV) is observed in only a small percentage of cats, it causes a systemic and often fatal disease. Diagnosis of feline infectious peritonitis (FIP) is challenging due to its non-specific clinical signs and the difficulty in differentiating between the two biotypes, feline enteric coronavirus (FECV) and FPIV. Currently, veterinarians rely on a combination of diagnostic methods, integrating laboratory tests, anamnesis and clinical signs to improve the diagnostic accuracy of FIP. Once considered untreatable, FIP now benefits from recent pharmacological advances that suggest promising therapeutic options, including antiviral drugs and immunomodulatory therapies. Despite these developments, the lack of an effective vaccine and definitive curative treatment highlights the need for continued research. This review provides a comprehensive analysis of the current literature on diagnostic and treatment approaches for FIP. The aim is to improve understanding of the available options and strategies for FIP to mitigate its severe consequences. Full article

Background/Objectives: Hypertension (HTN) remains a major global concern despite the availability of many antihypertensive medications, each with its own side effects. Lifestyle interventions, such as aerobic exercise and antioxidant-rich foods, represent promising non-pharmacological strategies for hypertension management. This study investigated the combined effects of exercise and vitamin C on anthropometric parameters, blood pressure, gut histology, biochemical markers, hematological profile, inflammatory gene expression, redox status, and stress hormones in L-nitroarginine methyl ester (L-NAME)-induced hypertensive rats. Methods: Male Wistar rats (n = 30) were randomly divided into five groups (n = 6/group): control, hypertensive (HTN), hypertensive + exercise (HTN + EX), hypertensive + vitamin C (HTN + VC), and hypertensive + exercise + vitamin C (HTN + EX + VC). Exercise consisted of treadmill training at a low intensity (50 ft/min) for 60 min daily, while vitamin C was administered orally (200 mg/kg/day) for four weeks. Blood pressure, anthropometric parameters, gut histology, inflammatory gene expression, hematological indices, serum biochemistry, oxidative stress markers, and hormonal assays were measured. Results: Both exercise and vitamin C individually reduced blood pressure (p < 0.05) and increased villi length (p < 0.05), upregulated anti-inflammatory cytokine expression in the gut, lowered oxidative stress (assessed through CRP, MDA, and catalase), and reduced stress hormones (cortisol and norepinephrine). The combined intervention (HTN + EX + VC) showed the most pronounced effects, resulting in a greater reduction in blood pressure and reversal of the changes induced by hypertension when compared to the HTN group. Conclusions: Exercise and vitamin C were beneficial in lowering blood pressure and improving the adverse changes associated with hypertension. Full article

Substance use disorder (SUD) is a chronic and clinically complex condition, frequently complicated by significant organic and psychiatric comorbidities. Most patients are polymedicated and require opioid substitution programs (OSPs). This complexity is further exacerbated by drug–drug interactions, therapeutic duplication, and fragmentation of the healthcare system. This retrospective observational study analyses the prevalence of polypharmacy and associated pharmacotherapeutic risks in a cohort of 1050 patients with SUD treated at Drug Care Units (DCUs) in Tenerife (Canary Islands, Spain). Prescriptions were dominated by methadone (62%), antidepressants, and antipsychotics, often in combination with benzodiazepines. Significant polypharmacy (>10 active prescriptions) was observed in 2.3% of patients, while 8.1% received 6–10 medications and 37.2% were using 2–5 medications. Women showed a higher pharmacological burden, with 3.5% experiencing significant polypharmacy (>10 different prescriptions) compared with 1.1% of men. Overall, 31% of patients received antidepressants, 31% were treated with antipsychotics—frequently with concurrent use of multiple agents—and 6.4% received opioids outside the OSP. Therapeutic duplication was observed in 15.6% of patients for psycholeptics, 14.2% for psychoanaleptics, and 3.2% for antiepileptics. Additionally, 25.2% of patients reported self-medication, predominantly with benzodiazepines. These findings underscore the need for integrated pharmaceutical care programs incorporating individualized therapeutic review and deprescribing strategies to enhance the safety and efficacy of SUD treatment. Full article

Inonotus obliquus (Chaga) is a medicinal basidiomycete fungus with diverse bioactive compounds and pharmacological properties. This study systematically compared green extraction techniques: maceration, ultrasound-assisted extraction (UAE), and combined supercritical CO₂-pressurized liquid extraction (ScCO₂-PLE), using solvents of varying polarity (water, 50%, and 70% ethanol). Chaga extracts were analyzed for phytochemical composition (HPLC-Orbitrap Exploris 120) and antioxidant activity toward DPPH and hydroxyl (^•OH) radicals using EPR spectroscopy. The results revealed that both solvent polarity and extraction technique significantly influenced extraction efficiency and antioxidant potential. The UAE extraction method achieved the highest overall recovery of phenolic and triterpenoid compounds, with extracts obtained using 50% and 70% ethanol exhibiting the most pronounced and well-balanced radical scavenging activity (>98% toward DPPH, >91% toward ^•OH). Correlation and PCA analyses identified phenolic and triterpenoid compounds, including fungal-specific polyphenols such as hispidin and hispolon, as key contributors to antioxidant activity. Among the extracts obtained using different solvents, the extracts with the highest overall antioxidant potential were encapsulated into liposomes and evaluated for their DPPH and ^•OH radical scavenging. Encapsulation effectively preserved the antioxidant activity of ethanol-derived extracts, demonstrating that Chaga liposomes can maintain bioactivity while offering the advantages of controlled delivery. Combining optimized extraction with liposomal encapsulation thus represents a promising strategy to enhance the stability and practical applicability of Chaga antioxidants in nutraceutical or therapeutic contexts. Full article