Search Results (24,216)

Background/Objective: The recurrence of hallux valgus (HV) after primary surgical correction remains a clinical challenge, often requiring combined approaches to address both bony realignment and soft tissue imbalance. While locking plates have shown some biomechanical advantages in HV correction, evidence regarding their application in revision procedures is limited. This study presents a retrospective single-surgeon experience with a small cohort, aiming to describe radiographic and functional outcomes and to share practical insights rather than provide definitive conclusions. Methods: In this retrospective case series, patients undergoing revision surgery for failed HV correction over the past ten years at a single tertiary institution were analyzed. Radiographic parameters—hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), and sesamoid position—were assessed. Functional outcomes included the American Orthopaedic Foot and Ankle Society (AOFAS) score and the Visual Analog Scale for pain. Surgical strategies were tailored according to recurrence mechanisms, and some cases involved Wilson osteotomy with intramedullary plate fixation. The Mann–Whitney U test and the Wilcoxon signed-rank test were applied to assess efficacy. Results: A total of 11 feet treated by one surgeon were included. Both soft tissue procedures and combined osteotomy with intramedullary plate fixation led to statistically significant but preliminary improvements in HVA, IMA, DMAA, and sesamoid alignment. Functional scores improved, and the complication rate was within the range reported in the previous literature. Conclusions: This retrospective single-surgeon study with a limited sample size suggests that Wilson osteotomy combined with intramedullary plate fixation may represent a joint-preserving and biomechanically supportive option for recurrent HV, particularly in cases with large DMAAs and severe sesamoid displacement. However, the findings should be interpreted cautiously given the small cohort, retrospective design, and absence of multi-angle radiographic visualization. The results highlight a potential approach in specific clinical settings rather than a definitive solution. Larger, prospective, multi-center studies are required to confirm long-term utility. Full article

Background: Diabetes-related foot diseases represent a global health problem because of the associated complications, the risk of amputation, and the economic burden on health systems. Negative pressure wound therapy (NPWT) is a technique that uses sub-atmospheric pressure to help promote wound healing by reducing the inflammatory exudate while keeping the wound moist, inhibiting bacterial growth, and promoting the formation of granulation tissue. Objective: This study aimed to assess the effectiveness of NPWT in preventing major amputation in diabetic patients with complicated foot or lower limb infections and to contextualize the results through a review of the existing literature. Materials and methods: We conducted a retrospective study at the First Surgical Department of “Dr. I. Cantacuzino” Clinical Hospital in Bucharest, Romania, over a 15-year period, including 30 consecutive adult patients with diabetes and soft tissue foot or lower limb infections treated with NPWT. Patients with non-diabetic ulcers, incomplete medical data, or aged under 18 were excluded. All patients underwent initial surgical debridement, minor amputation, or drainage procedures, followed by the application of NPWT using a standard protocol. Dressings were changed every 2–4 days for a total of 7–10 days. Antibiotic therapy was adapted according to the culture results. The primary outcome was limb preservation, defined as avoidance of major amputation. Secondary outcomes included in-hospital mortality and wound status at discharge. Results: NPWT was associated with a favorable outcome in 24 patients (80%), defined by wound granulation or healing without the need for major amputation. Five patients (16.6%) underwent major amputation because of failure of the primary lesion treatment, and one patient died. No statistically significant association was observed between the outcomes and standard classification scores (WIFI, IWGDF, and TPI). A comprehensive literature review helped to integrate these findings into the existing pool of knowledge. Conclusions: NPWT may support limb preservation in selected diabetic foot cases. While the retrospective design and the small sample size of the study limit generalizability, these results reinforce the need for further controlled studies to evaluate NPWT in real-life clinical settings. The correct use of NPWT combined with etiological treatment may offer a maximum chance to avoid major amputation in patients with diabetes-related foot diseases. Full article

Decellularized extracellular matrix (dECM) scaffolds preserve native tissue structure and biochemical cues while minimizing immune responses, creating biomimetic templates that promote cell integration and tissue remodeling. This review examines the current state of dECM research, encompassing decellularization methods, scaffold quality evaluation assays, and tissue-specific applications across dermis, nerve, heart, lung, adipose, and placental ECMs. We analyze commercially available dECM products and ongoing clinical trials, while highlighting recent advances including 3D bioprinting and the integration of dECM with stem cells and growth factors. Despite these promising developments, several challenges continue to limit broader clinical translation: protocol standardization, residual immunogenicity, mechanical durability, and regulatory, manufacturing, and cost barriers. To address these limitations, we outline future directions focusing on patient-specific scaffolds, scalable bioprocessing, and integrated biofabrication strategies that will enable the development of safe and effective dECM-based therapies. Full article

Background: Vitamin K antagonist oral anticoagulant (VKA) therapy, using warfarin or acenocoumarol in our health system, is indicated, according to clinical guidelines, for the prophylaxis of thromboembolic events. In Málaga, the VKA patient management program currently includes a total of 856 patients. Hypothesis: The use of an AI-based application can enhance treatment adherence among VKA patients participating in self-monitoring and self-management programs. Furthermore, it can support the comprehensive implementation of the system, leading to reduced costs and fewer interventions for anticoagulated patients. Methods: The study will be conducted in several phases. The first phase involves the development of the application and the integration of Artificial Intelligence (AI) and Machine Learning (ML) algorithms. The second phase includes preliminary testing and validation of the developed application. The third phase consists of full implementation, along with an assessment of user-identified needs and potential quality improvements. Expected Results: The implementation of the AIto-Control app is expected to reduce healthcare-related costs by decreasing primary care visits and hospital admissions due to thromboembolic or bleeding events. Additionally, it aims to ease the workload on both primary care and hospital services. These outcomes will be achieved through the involvement of advanced practice nurses who will supervise app-based monitoring and patient education. Full article

Background: The accurate and rapid genotyping of ABO (chromosome 9q34.2) blood types is critical for clinical diagnostics and transfusion medicine, particularly in scenarios where serological methods yield uncertain results, such as in neonatal testing or with rare ABO subtypes. Methods: This study describes a loop-mediated isothermal amplification (LAMP)-based method for ABO genotyping that offers a faster and more cost-effective alternative to conventional PCR-based techniques. Results: The method targets four key single nucleotide polymorphisms (SNPs) at positions 261, 297, 703, and 930, allowing for the differentiation of common A, B, and O blood types, as well as the rare AB subtype B(A)01. The detection of the B(A)01 subtype is clinically important for preventing transfusion mismatches where serology may be inconclusive. Operating at a constant temperature, the assay can be completed in under an hour without the need for a thermocycler, offering significant time and cost benefits over qPCR. The method demonstrated high specificity, demonstrating detection down to 10 copies across all assays. When validated against a gold-standard method on clinical blood samples, the LAMP assay showed high accuracy (95% C value calculated via binomial exact method): 97.4% for type O, 98.7% for type A, 98.7% for type B, and 100% for the B(A)01 subtype. To enhance usability for point-of-care applications, freeze-dried reagents were developed that permit direct loading of lysed blood samples while maintaining high performance. Conclusions: This simplified and robust format positions the LAMP assay as a promising tool for rapid and reliable ABO genotyping in diverse clinical settings. Full article

The escalating crisis of bacterial antimicrobial resistance poses a severe threat to global health, necessitating novel strategies beyond conventional antibiotics. Photothermal therapy (PTT) has emerged as a promising alternative that leverages heat generated by laser irradiation to induce localized cellular damage and eradicate bacteria. Among various photothermal agents, carbon-based nanomaterials like graphene nanoplatelets (GNPs) offer exceptional properties for PTT applications. This study introduces a novel urinary catheter (UC) embedded with GNPs (GNPUC), specifically designed for photothermal sterilization to combat catheter-associated bacterial infections. GNPs were systematically incorporated into polydimethylsiloxane (PDMS) catheters at varying weight percentages (1% to 10%). The fabricated GNPUCs exhibited low wettability, hydrophobic characteristics, and low adhesiveness, properties that are crucial for minimizing bacterial interactions and initial adhesion. Upon exposure to near-infrared (NIR) laser irradiation (808 nm, 1.5 W/cm²), the UC containing 10 weight percent of GNPs (10GNPUC) achieved a significant temperature of 68.8 °C, demonstrating its potent photothermal conversion capability. Quantitative agar plate tests confirmed the enhanced, concentration-dependent photothermal antibacterial activity of GNPUCs against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Notably, 5% and higher GNP concentrations achieved 100% mortality of S. aureus, while 1% and higher concentrations achieved 100% mortality of E. coli. These findings underscore the significant potential of GNP-embedded catheters as a highly effective photothermal antibacterial platform for future clinical applications in combating catheter-associated infections. Full article

Background: Adhesion to enamel is influenced by surface preparation, which affects the micromechanical retention of resin-based materials. Sodium hypochlorite (NaOCl) deproteinization has been proposed as a pretreatment to improve acid etching efficacy, but the optimal application time remains unclear. Methods: This in vitro study evaluated the effect of 5% NaOCl pretreatment at three exposure times (15, 30, and 60 s) on shear bond strength (SBS), the adhesive remnant index (ARI), and enamel etching patterns. Extracted human premolars (n = 140) were divided into four groups: the control (acid etching only) and three experimental groups. SBS was tested per ISO 11405, while ARI scores were assessed under stereomicroscopy, and surface morphology was examined by scanning electron microscopy (SEM). Results: The 30-s NaOCl group exhibited the highest SBS (20.9 MPa) compared with the control (15.9 MPa, p < 0.05) and 15-s (14.9 MPa, p < 0.05) groups. SEM analysis showed predominantly Type I–II etching patterns for the 30-s group, irregular Type III for 15 s, and overetched Type IV with loss of prism definition for 60 s, compromising the adhesive interface. ARI scores indicated 86.7% of samples in the 30-s group retained all adhesive on enamel (score 3). Conclusions: A 30-s 5% NaOCl pretreatment before acid etching improved enamel micromorphology and bonding performance compared to shorter or longer exposures. The intermediate duration provided effective deproteinization without structural damage, whereas prolonged exposure degraded the enamel microstructure. This protocol may offer a simple, cost-effective method to enhance clinical adhesive procedures, though prolonged exposure (60 s) should be avoided due to structural degradation of the enamel microstructure. Full article

Vitamin D₃ plays a pivotal role not only in bone health but also in the functioning of the nervous system, particularly in the context of age-related neurodegenerative diseases such as Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Vitamin D₃ deficiency has been associated with cognitive decline, heightened inflammation, and shortened leukocyte telomere length, which may contribute to accelerated cellular aging. Therapeutic interventions involving vitamin D₃ have been reported in selected clinical studies and meta-analyses to potentially enhance cognitive function, decrease amyloid β biomarkers, and prolong telomere length, although heterogeneity remains across study designs and populations. Furthermore, vitamin D₃ has been shown to influence the expression of genes implicated in DNA repair and oxidative stress response, including NRF2, OGG1, MYH, and MTH1. This narrative review synthesizes current knowledge on the molecular mechanisms of vitamin D₃ action in the context of neuroprotection and discusses potential directions for future research, including its possible therapeutic applications in neurodegenerative diseases. Full article

Adenosine plays a crucial role in various pathophysiological conditions, including neuroinflammation and neurodegeneration. Neuroinflammation can be either beneficial or detrimental to the central nervous system, depending on the intensity and duration of the inflammatory response. Across a wide range of brain disorders, neuroinflammation contributes to both the onset and progression of disease. Notably, neuroinflammation is not limited to conditions primarily classified as neuroinflammatory but is also a key factor in other neurological disorders, including life-threatening neurodegenerative diseases. All four adenosine receptor subtypes (A₁, A_2A, A_2B, and A₃) are implicated, to varying degrees, in these conditions. This review aims to summarize the roles of individual adenosine receptor subtypes in neuroinflammation and neurodegenerative diseases, emphasizing their therapeutic potential. While some therapeutic applications are well-established with clinically approved drugs, others warrant further investigation due to their promising potential. Full article

Parasites of the Leishmania genus are globally distributed and cause various clinical presentations in animals and humans, collectively known as leishmaniasis. The genomes of Leishmania and other trypanosomatids exhibit remarkable plasticity, shaped by several distinctive genetic features. Although these features can hinder the application of next-generation DNA sequencing (NGS) technologies, NGS data have been successfully used to characterize the whole-genome diversity of circulating Leishmania strains. The results complement and are broadly aligned with previous findings obtained with more traditional methods, offering greater resolution when working with geographically closer strains. In this review, we summarize advances over the past two decades in characterizing the genome diversity of Leishmania parasites using NGS strategies. We also discuss the application of these strategies to elucidate other aspects relevant to the epidemiology of these parasites, including their population structure and mode of reproduction. The vast majority of the studies to date have focused on species within the L. donovani/infantum complex or the L. (Viannia) subgenus, highlighting the need to incorporate other relevant underrepresented species and regions from both the Old and New World. Full article

Background: The emergence of pan-drug-resistant (PDR) Klebsiella pneumoniae has compromised the efficacy of last-line agents, leaving few therapeutic options. Repurposing zidovudine, an FDA-approved thymidine analog with antibacterial activity, may enhance existing therapies, but pharmacodynamic data under clinically relevant conditions are scarce. This study addresses this gap using static and dynamic in vitro models. Materials/methods: A PDR strain of Klebsiella pneumoniae harboring bla_NDM-1, bla_CMY-6, bla_CTX-M-15, bla_SHV-2, and disrupted mgrB was used in this study. Minimum inhibitory concentrations (MICs) followed by static time-kills were performed to investigate the synergistic interplay between zidovudine and last-line antibiotics (ceftazidime/avibactam, polymyxin B). To simulate human pharmacokinetics, a hollow-fiber infection model (HFIM) was employed using steady-state concentrations of zidovudine (4 mg/L), polymyxin B (4 mg/L), and avibactam (22 mg/L). Structural and morphological effects on bacterial cells were examined via fluorescence microscopy following glutaraldehyde fixation. Results: In this study, the PDR K. pneumoniae showed a ~5-fold reduction in polymyxin MIC when combined with zidovudine (from >4 µg/mL to 0.25 µg/mL). Time-kill assays demonstrated ≥2.5 log₁₀ CFU/mL bacterial reduction with zidovudine-based combinations, whereas monotherapies failed to inhibit bacterial growth. In the HFIM, the triple combination achieved rapid bactericidal activity (>3 log₁₀ CFU/mL reduction within 4 h) and sustained killing (>5–6 log₁₀ reduction maintained through 216 h), with bacterial counts remaining below 1 CFU/mL. In contrast, dual combinations initially reduced bacterial burden (1–3 log₁₀ reduction) but failed to maintain suppression, with significant regrowth (>10¹⁰ CFU/mL) observed by 168 h. Microscopy corroborated these findings, revealing extensive cellular damage in the zidovudine-containing treatment arms. These HFIM results underscore the potential of zidovudine-based triple therapy in overcoming resistance to last-line antibiotics in K. pneumoniae. Conclusions: Our results provide promising unprecedented insight into novel zidovudine-based combination therapies against difficult-to-treat MBL Gram-negatives. The observed synergy in MIC reduction, rapid killing in time-kill assays, and near-complete eradication in the HFIM underscore the therapeutic potential of this triple combination. Future studies will focus on broadening the application of these novel combinations to other ‘superbugs’, such as highly resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa. Full article

Scorpion venom is a rich source of bioactive compounds with significant potential for anticancer drug development. Its diverse molecular composition, including neurotoxins, antimicrobial peptides, and enzymes, provides a vast library for therapeutic innovation. Proteomic analyses have characterized venom composition in several species, while further functional assays have clarified their anticancer mechanisms. This review synthesizes current knowledge on scorpion venom-derived peptides with demonstrated anticancer activity, which selectively target ion channels, induce apoptosis, or disrupt tumor microenvironments. Where available, we highlight proteomic studies that have identified these components and discuss their structural features relevant to drug design. We also examine clinical applications and the challenges in translating venom peptides into therapies. The crucial and growing role of proteomics in this field, particularly for venom fractionation, component identification, and structural characterization, is critically evaluated. Full article

Ginsenosides, the primary bioactive components of Panax ginseng, have demonstrated significant immunomodulatory potential. While major ginsenosides have been extensively studied, rare ginsenosides produced through deglycosylation, heating, and steaming show enhanced biological activities with improved bioavailability. This review aimed to comprehensively analyze the immunomodulatory mechanisms, structure-activity relationships (SARs), therapeutic applications, and clinical translation strategies of five emerging rare ginsenosides: F1, Rg5, Rk1, Rh1, and Rg2. We conducted a comprehensive literature review examining the production methods, immunological effects, molecular mechanisms, pharmacokinetics, safety profiles, and clinical applications of these five compounds. Analysis focused on chemical structures, immune cell modulation, signaling pathways, disease model efficacy, and bioavailability enhancement strategies. Ginsenoside F1 uniquely demonstrated immunostimulatory effects, enhancing natural killer (NK) cell cytotoxicity and macrophage phagocytosis through mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) activation. Conversely, Rg5, Rk1, Rh1, and Rg2 exhibited anti-inflammatory properties via distinct mechanisms: Rg5 through Toll-like receptor 4 (TLR4)/NF-κB inhibition, Rk1 via triple pathway modulation (NF-κB, p38 MAPK, signal transducer and activator of transcription (STAT)), Rh1 by selective p38 MAPK and STAT1 inhibition, and Rg2 through modulation of both central nervous system (neuroinflammation) and peripheral organ systems. Structure-activity analysis revealed that sugar moiety positions critically determine immunological outcomes. Crucially, advanced delivery systems including nanostructured lipid carriers, self-microemulsifying systems, and specialized liposomes have overcome the major translational barrier of poor bioavailability, achieving up to 2.6-fold improvements and enabling clinical development. Safety assessments demonstrated favorable tolerability profiles across preclinical and clinical studies. These five rare ginsenosides represent promising immunomodulatory agents with distinct therapeutic applications. F1’s unique immunostimulatory properties position it for cancer immunotherapy, while the complementary anti-inflammatory mechanisms of Rg5, Rk1, Rh1, and Rg2 offer opportunities for precision medicine in inflammatory diseases. Advanced formulation technologies and optimized production methods now enable their significant clinical translation potential, providing promising therapeutic options for immune-related disorders pending further development. Full article

Chilean hop (Humulus lupulus L.) ecotypes are an under-explored resource with high bioactive potential, offering promising applications in food preservation and health promotion. This study aimed to characterize the chemical composition and evaluate the antioxidant, antimicrobial, and cytotoxic properties of methanolic extracts from three native ecotypes—Ranco, La Unión, and Valdivia—to identify their potential as sources of multifunctional bioactive compounds. Each ecotype exhibited a distinct composition of bioactive compounds; Valdivia stood out for its pronounced levels of α- and β-acids and xanthohumol. Antioxidant capacity, assessed by DPPH, FRAP, and ABTS, was strong across extracts, with Valdivia showing the highest values in all the tests carried out. The extracts inhibited multidrug-resistant clinical isolates, notably Enterococcus faecalis and Pseudomonas aeruginosa, and showed dose-dependent cytotoxic effects in H1299 and MCF-7 cell lines, with the La Unión extract particularly active against H1299. Overall, these findings position Chilean hop ecotypes as promising sources of natural antioxidants and antimicrobial agents for functional food and nutraceutical applications. Full article

Background: Remote ischemic conditioning (RIC) has shown promise as a neuroprotective strategy, but its application in children with cerebral palsy (CP) remains unexplored. We conducted a randomized controlled trial to evaluate the feasibility, safety, and tolerability of repeated, 6–7 sessions of RIC in children with unilateral CP. Methods: Fifty-one children aged 6–16 years with unilateral CP were randomized (1:1) to receive RIC or sham conditioning on the more affected arm. Primary feasibility outcomes included recruitment metrics, intervention adherence, retention, and protocol fidelity. Safety endpoints included continuous monitoring of oxygen saturation, blood pressure, heart rate, and adverse event incidence. Tolerability was assessed via child-reported pain ratings, conditioning pressure tolerance, skin integrity evaluations, and session adherence. Results: Of 148 children screened, 51 were randomized to RIC (n = 25), sham (n = 26) groups; 48 (94.1%) completed the intervention as allocated. Recruitment yielded 2.04 participants/month. Intervention adherence was 100% in both groups. RIC was well tolerated, with mean pain scores 2.8 ± 3.1 during inflation in RIC and 0.3 ± 0.8 in Sham group. No serious adverse events occurred. Physiological parameters remained stable across 314 conditioning sessions; no clinically significant hypoxemia, blood pressure derangements, or arrhythmias were detected. Minor adverse events (transient erythema, mild discomfort) were rare (2.22%) and self-limiting. Skin integrity was preserved, and no participants required session termination. Conclusions: Repeated RIC is feasible, safe, and tolerable in children with unilateral CP. These findings support the design of future trials using RIC as a priming agent to enhance pediatric neurorehabilitation outcomes. Full article