Search Results (88)

Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease (ESKD) globally. Despite advances in our understanding of its pathophysiology, current therapies are often insufficient to stop its progression. In recent years, microRNAs (miRNAs)—small, non-coding RNA molecules involved in post-transcriptional gene regulation—have emerged as critical modulators of key pathogenic mechanisms in DKD, including fibrosis, inflammation, oxidative stress, and apoptosis. Numerous studies have identified specific miRNAs that either exacerbate or mitigate renal injury in DKD. Among them, miR-21, miR-192, miR-155, and miR-34a are associated with disease progression, while miR-126-3p, miR-29, miR-146a, and miR-215 demonstrate protective effects. These molecules are also detectable in plasma, urine, and renal tissue, making them attractive candidates for diagnostic and prognostic biomarkers. Advances in therapeutic technologies such as antagomiRs, mimics, locked nucleic acids, and nanoparticle-based delivery systems have opened new possibilities for targeting miRNAs in DKD. Additionally, conventional drugs, including SGLT2 inhibitors, metformin, and GLP-1 receptor agonists, as well as dietary compounds like polyphenols and sulforaphane, may exert nephroprotective effects by modulating miRNA expression. Recent evidence also highlights the role of gut microbiota in regulating miRNA activity, linking metabolic and immune pathways relevant to DKD progression. Further research is needed to define stage-specific miRNA signatures, improve delivery systems, and develop personalized therapeutic approaches. Modulation of miRNA expression represents a promising strategy to slow DKD progression and improve patient outcomes. Full article

Background/Objectives: Vancomycin (V) is widely used for catheter lock therapy. However, its ad hoc preparation in pharmacy departments involves discarding most of an intravenous vial and contributes to high workload. We aimed to assess the V concentration and minimum inhibitory biofilm concentration (MIBC) of a frozen V lock solution. Methods: Two V-2 mg/mL solutions were tested: (1) V + heparin 100 IU/mL and (2) V + citrate 2%. Solutions were frozen at −20 °C, followed by 48 h refrigeration, and analyses were performed at baseline and after 2, 4, 8, and 12 weeks (experiment 1). In addition, after the 12-week freezing period, solution 1 was also preserved for 1 and 2 weeks at both 4 °C and room temperature (experiment 2). V concentration was assessed by HPLC-DAD at 205 nm and validated with forced degradation tests. A <10% variation indicated significant change. MBIC was determined by XTT staining of 24 h biofilms exposed to decreasing concentrations of each solution. Microorganisms tested included methicillin-susceptible and -resistant Staphylococcus aureus (MSSA, MRSA), Staphylococcus epidermidis ATCC35984 (SE), and a highly biofilm-forming clinical S. epidermidis strain (SEclin). MIBC was defined as ≥50% reduction in metabolic activity. Results: In experiment 1, while V concentration remained stable over time, MIBC values varied, notably increasing from 8 weeks for all strains. Moreover, in experiment 2, significant reductions in both V concentration and MIBC were detected in the 2-week period. Conclusions: V lock solution appears to be able to be 12-weeks frozen followed by up to 1 week at refrigeration or room temperature. This facilitates the optimization of vial preparation in hospital pharmacy laboratories. Full article

Staphylococcus aureus are frequently associated with biofilm formation on intravascular devices. Biofilms limit antimicrobial penetration and promote phenotypic resistance, challenging conventional treatment strategies. Vancomycin (VAN) and gentamicin (GEN) have been used clinically, but their combined antibiofilm activity remains underexplored. This study evaluates the efficacy of VAN and GEN, alone and in combination, against biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) on polyurethane. MICs were determined for VAN and GEN. Biofilm biomass and metabolic activity were quantified using crystal violet and MTT assays, respectively. Biofilm viability was assessed through fluorescence microscopy and a modified Calgary Biofilm Device. A continuous-flow peristaltic model was developed to test treatment under simulated catheter conditions. While monotherapy with VAN or GEN had modest effects, their combination significantly reduced biomass and metabolic activity. VAN 20 mg/L + GEN 8 mg/L and VAN 40 mg/L + GEN 8 mg/L achieved over 70% reduction in MRSA biofilm viability and complete eradication in MBEC assays. Dynamic model assays confirmed biofilm reduction with combination therapy. The combination of VAN/GEN exhibits synergistic antibiofilm activity against S. aureus, particularly MRSA. These findings support its potential application in catheter salvage strategies, including antibiotic lock therapy. Full article

Objectives: This study aims to evaluate the use and efficacy of antibiotic-lock therapy (ALT) in the management of catheter-related bloodstream infections (CRBSIs), focusing on its impact on infection resolution, catheter retention, and clinical outcomes. Methods: Patients aged ≥18 years diagnosed with CRBSIs who had long-term indwelling catheters and for whom catheter replacement posed clinical challenges were enrolled in the retrospective study from January 2019 to December 2024. Participants were divided into two groups based on treatment: Group 1 received intravenous (IV) antibiotics combined with antibiotic-lock therapy (ALT), while Group 2 received IV antibiotics alone. Patient demographics, pathogen distribution, administered antibiotic regimens, duration of treatment, laboratory parameters, clinical outcomes, and mortality rates were evaluated. Results: A total of 54 patients were included, of whom 42.6% were female, and the mean age was 66.3 ± 15.4 years. Group 1 comprised 50% of the study population. The median treatment duration was 14 days. The most common pathogen was Coagulase-negative staphylococci, and 33.3% of CRBSIs were caused by Gram-negative bacteria (GNB). Group 1 demonstrated lower C-reactive protein levels at treatment 48/72 h of treatment (p = 0.013) and a reduced frequency of catheter revision (p < 0.0001) compared to Group 2. Overall, ALT achieved a success rate of 88.9%, with success rates of 86% for GNB infections and 90% for Gram-positive bacterial infections. Among patients receiving daily ALT, the success rate was 86%, while those receiving the therapy every three days had a success rate of 90%. Conclusions: Antimicrobial lock therapy can be considered a treatment option for managing CRBSIs, particularly in cases where removal of the implantable catheter is not feasible, allowing for salvage. Full article

Background/Objectives: Epilepsy is a common neurological disorder that not only severely impacts patients’ health but also imposes a significant burden on families and society. However, its pathogenesis remains unclear. Astrocytes play a crucial role in epileptic seizures and may serve as potential therapeutic targets. Establishing a network model of epileptic seizures based on the astrocyte–neuron cell coupling and the clinical electroencephalographic (EEG) characteristics of epilepsy can facilitate further research on refractory epilepsy and the development of treatment strategies. Methods: This study constructs a neuronal network dynamic model of epileptic seizures based on the Watts–Strogatz small-world network, with a particular emphasis on the biological mechanisms of astrocyte–neuron coupling. The phase-locking value (PLV) is used to quantify the degree of network synchronization and to identify the key nodes or connections influencing synchronous seizures, such that two epilepsy treatment strategies are proposed: seizure suppression through stimulation and surgical resection simulation therapy. The therapeutic effects are evaluated based on the PLV-quantified network synchronization. Results: The results indicate that the desynchronization effect of random noise and sinusoidal wave stimulation is limited, while square wave stimulation is the most effective. Among the four surgical resection strategies, the effectiveness is the highest when resecting nodes exhibiting epileptic discharges. These findings contribute to the development of rational seizure suppression strategies and provide insights into precise epileptic focus localization and personalized treatment approaches. Full article

Delftia acidovorans (D. acidovorans) is a non-fermentative, aerobic, Gram-negative bacillus typically found in environmental sources such as soil and water. Although considered an opportunistic pathogen, it has been implicated in both immunocompromised and immunocompetent individuals. This study presents a case of persistent cathether-related bacteraemia in a 61-year-old haemodialysis patient and offers a systematic literature review of similar cases. The patient, affected by end-stage kidney disease and dependent on a central venous catheter (CVC), presented with septic shock. Blood cultures confirmed D. acidovorans, resistant to aminoglycosides but sensitive to cephalosporins, piperacillin/tazobactam, and fluoroquinolones. Despite appropriate antibiotic therapy, bacteraemia persisted, prompting the use of taurolidine lock therapy when catheter removal was initially unfeasible. Blood cultures cleared after nine days, and the catheter was later replaced. A systematic review following PRISMA guidelines identified 21 additional cases of D. acidovorans bacteraemia. Most (76.2%) occurred in immunocompromised patients, particularly those with malignancies, chronic haemodialysis, or indwelling devices. Infections in immunocompetent individuals were typically associated with intravenous drug use or environmental exposure. Mortality was approximately 19%. Aminoglycoside resistance was consistent across most cases, while susceptibility to piperacillin/tazobactam, cephalosporins, and carbapenems was generally preserved. Given its resistance profile and ability to form biofilms, D. acidovorans poses a management challenge, particularly in catheter-associated infections. Rapid identification and targeted antimicrobial therapy are crucial. Adjunctive measures such as taurolidine lock therapy can be beneficial when device removal is not immediately possible. Full article

Deucravacitinib is an allosteric, selective tyrosine kinase 2 (TYK2) inhibitor that has demonstrated significant efficacy in the treatment of psoriasis. TYK2, a member of the Janus kinase (JAK) family, plays a critical role in intracellular signaling pathways for pro-inflammatory cytokines. Unlike traditional JAK inhibitors, which target active domains, deucravacitinib selectively binds to the pseudokinase domain of TYK2. This binding induces a conformational change that locks the enzyme in an inactive state, ensuring superior selectivity for TYK2 over JAK 1/2/3. This unique mechanism specifically inhibits key pro-inflammatory cytokines, including IL-12, IL-23, and type I interferons, critical in the pathogenesis of psoriasis and other immune-mediated diseases. As a result, deucravacitinib represents a promising option for targeted therapy in immune-mediated diseases and may reduce adverse events commonly associated with broader immunosuppressive treatments. Furthermore, its oral administration offers a convenient alternative to injectable biologics, potentially improving patient adherence and treatment satisfaction. This review highlights recent studies suggesting that deucravacitinib may also have therapeutic benefits in psoriatic arthritis, palmoplantar pustulosis, systemic lupus erythematosus, Sjogren’s disease, and inflammatory bowel disease. Given its expanding therapeutic potential, deucravacitinib may provide a safer and more effective alternative to current therapies, offering a tailored approach to treatment. Full article

Antimicrobial lock therapy (ALT) prevents microbial colonization in central vein catheters and treats existing catheter-related bloodstream infections (CRBSIs); the ALT assessment involves several key considerations. First, identifying which patients are suitable candidates is crucial. Additionally, understanding the clinical contexts in which is utilised provides insight into its applications. Examining when ALT has been employed and analyzing trends in its use over time can highlight its evolving role in patient care. Equally important is understanding how ALT is administered, including the specific agents used. Lastly, determining whether there is sufficient existing literature is essential to evaluate the feasibility of conducting future systematic reviews. This study is a scoping review adhered to the PRISMA-ScR guidelines and followed a five-stage methodological framework. Of the 1024 studies identified, 336 were included in the analysis. Findings highlight the widespread use of ethanol and taurolidine for CRBSIs prevention and the concurrent use of ALT with systemic antimicrobials to treat CRBSIs without catheter removal. ALT improves clinical outcomes, including post-infection survival and catheter retention. From our analysis, we have concluded that both an umbrella review of systematic reviews and a network meta-analysis comparing lock solutions can provide clearer guidance for clinical practice. Full article

Healthcare-associated infections pose a significant global health challenge, negatively impacting patient outcomes and burdening healthcare systems. A major contributing factor to healthcare-associated infections is the formation of biofilms, structured microbial communities encased in a self-produced extracellular polymeric substance matrix. Biofilms are critical in disease etiology and antibiotic resistance, complicating treatment and infection control efforts. Their inherent resistance mechanisms enable them to withstand antibiotic therapies, leading to recurrent infections and increased morbidity. This review explores the development of biofilms and their dual roles in health and disease. It highlights the structural and protective functions of the EPS matrix, which shields microbial populations from immune responses and antimicrobial agents. Key molecular mechanisms of biofilm resistance, including restricted antibiotic penetration, persister cell dormancy, and genetic adaptations, are identified as significant barriers to effective management. Biofilms are implicated in various clinical contexts, including chronic wounds, medical device-associated infections, oral health complications, and surgical site infections. Their prevalence in hospital environments exacerbates infection control challenges and underscores the urgent need for innovative preventive and therapeutic strategies. This review evaluates cutting-edge approaches such as DNase-mediated biofilm disruption, RNAIII-inhibiting peptides, DNABII proteins, bacteriophage therapies, antimicrobial peptides, nanoparticle-based solutions, antimicrobial coatings, and antimicrobial lock therapies. It also examines critical challenges associated with biofilm-related healthcare-associated infections, including diagnostic difficulties, disinfectant resistance, and economic implications. This review emphasizes the need for a multidisciplinary approach and underscores the importance of understanding biofilm dynamics, their role in disease pathogenesis, and the advancements in therapeutic strategies to combat biofilm-associated infections effectively in clinical settings. These insights aim to enhance treatment outcomes and reduce the burden of biofilm-related diseases. Full article

Introduction: Vascular access device (VAD)-associated infections, including catheter-related (CRBSI) and catheter-associated bloodstream infections (CABSI), present significant challenges in patient care. While multidisciplinary VAD teams (VATs) are equipped with protocols for managing these infections, adherence to these guidelines in real-life practice is inconsistent. This study aims to evaluate the alignment between actual VAD infection management practices and VAT-recommended protocols. Methods: We conducted a retrospective, single-center study at Luigi Sacco Hospital (May 2021–October 2023) involving non-ICU adult patients with diagnosed CRBSI or CABSI. VAT experts independently reviewed infection management choices, which were divided into eight specific procedural options. These options included variations in VAD removal, timing of repositioning, and combinations of antimicrobial lock therapy and systemic therapy. Concordance between real-life practices and VAT recommendations was evaluated using Cohen’s kappa coefficient. Results: Of 2419 VAD placements, 146 (6%) developed infections (84 CABSI, 62 CRBSI). Clinicians removed VADs in 66.4% of cases compared to 62.3% per VAT recommendations, with moderate overall agreement (Cohen’s kappa = 0.58). Analysis of the eight management categories revealed moderate to low alignment (unweighted kappa = 0.44, weighted kappa = 0.30) between real-life practices and VAT guidance, with slightly improved concordance in CRBSI cases. Conclusions: Our findings underscore a discrepancy between real-life VAD infection management and VAT-recommended protocols, suggesting a need for clearer, more accessible guidelines and increased multidisciplinary collaboration. Enhanced VAT consultation and simplified protocol dissemination may improve consistency in infection management and ultimately lead to better patient outcomes. Full article

Candida forms a gel-like biofilm in the Foley’s catheter (FC) causing tenacious biofouling and severe urinary tract infections (UTIs). For the first time, a spice extract-based antifungal lock therapy (ALT) has been developed to inhibit the Candida albicans gel matrix in FC. Aqueous extracts of garlic, clove, and Indian gooseberry were used as ALT lock solutions and tested against biofilm-forming multidrug-resistant clinical isolates of C. albicans. Reduction in the gel matrices formation in the catheter was confirmed by Point inoculation, MTT assay, CFU, and SEM analysis at 12 and 24 h of incubation. Garlic was effective in controlling both C. albicans M207 and C. albicans S470; however, clove and gooseberry effectively controlled the latter. As evidenced by CFU assay, there were 82.85% and 99.68% reductions in the growth of C. albicans M207 and S470, respectively, at 24 h of incubation. SEM revealed a switch from the biofilm to the yeast mode and a drastic reduction in cell numbers, with mostly clumped or lysed cells. The study will provide an impetus to the development of novel spice extract-based ALT, reducing the selection pressure on the pathogen and lowering antimicrobial resistance. Further research in this area has the potential to leverage clinical applications. Full article

Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, “Shock and kill”, “Block and lock”, and the application of broad-spectrum neutralizing antibodies (bNAbs). Full article

Background: Temporomandibular joint disc displacement with reduction is one of the most common types of TMJ arthropathy. This single-blinded, randomized clinical study aimed to evaluate the effectiveness of three different therapeutic methods. Methods: Standard splints (Group 1), modified occlusal splint (Group 2), and conventional physical therapy with exercises (Group 3). A total of 48 patients were randomly assigned by a computer-generated allocation sequence to receive rehabilitation. The outcome was defined as improvements in pain and intermittent locking episodes. The follow-up visits were scheduled as one month and a long-term evaluation at one (T1), two (T2), three (T3), and four years (T4). Magnetic resonance images were also taken to evaluate each patient before treatment and at one year. Image analysis involved the evaluation of morphology and the function of intra-articular structures. Variables such as age, gender, and pre- vs. post-treatment values of VAS and TMJ locks between the three intervention categories were compared for statistical evaluations. p values ≤ 0.05 were taken as being significant. Results: A total of 16 subjects were allocated to each group. At T1, a decrease in pain and TMJ locking episodes was observed, which was maintained throughout the course of the study for four years of follow-ups, with no statistically significant differences. However, there was a tendency for better outcomes in favor of Group 2, with less clicking of the TMJ at opening. Conclusions: The modified mandibular splint seems to be successful as an effective alternative for the management of temporomandibular joint disc displacement with reductions in intermittent locking. Full article

Yoga enhances acceptance, compassion, physicality, mental and emotional awareness, and spiritual benefits through breath techniques, postures, and body locks, while swimming improves flexibility, strength, and body awareness. The fusion of yoga and swimming, particularly the aqua yoga asana method, offers a balanced lifestyle for athletes and non-performers, enhancing their performance. Our study examined the feasibility of incorporating yoga and swimming practice into Romanian subjects’ lifestyles, designing a factor analysis in SmartPLS software, based on an online survey. This study assessed participants’ knowledge of yoga’s theory and philosophy, as well as their perceptions of the benefits of swimming practice for social and health issues. Our 250 young swimming athletes train in Bucharest’s sports clubs. According to our study, Romanian participants practice yoga and swimming as often as possible to reduce stress, improve concentration for work-related tasks, and improve joint elasticity, balance, and muscular tone. The high coefficient of path analysis (0.667) proved that those who practice yoga asanas have a high level of awareness and understand the fundamentals of the practice. The second coefficient of path analysis (0.857) shows that those who understand yoga better are convinced of its positive effects on society and their health. Thus, yoga and swimming are substitutes for other approaches in prevention and therapy, making it a beneficial tool for pre-performance swimming. Full article

Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure has remained elusive. Elimination of latent HIV reservoirs that persist throughout HIV infection is the most challenging barrier to an HIV cure. The progressive HIV infection is marked by the increasing size and diversity of latent HIV reservoirs until an effective immune response is mobilized, which can control but not eliminate HIV infection. The stalemate between HIV replication and the immune response is manifested by the establishment of a viral set point. ART initiation during the early stage limits HIV reservoir development, preserves immune function, improves the quality of life, and may lead to ART-free viral remission in a few people living with HIV (PLWH). However, for the overwhelming majority of PLWH, early ART initiation alone does not cure HIV, and lifelong ART is needed to sustain viral suppression. A critical area of research is focused on determining whether HIV could be functionally cured if additional treatments are provided alongside early ART. Several HIV interventions including Block and Lock, Shock and Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell therapy, and gene therapy have demonstrated delayed viral rebound and/or viral remission in animal models and/or some PLWH. Whether or not their application during early infection can improve the success of HIV remission is less studied. Herein, we review the current state of clinical and investigative HIV interventions and discuss their potential to improve the likelihood of post-treatment remission if initiated during early infection. Full article