Search Results (19,226)

Lactoferrin (LF) is an 80 kDa iron-binding glycoprotein primarily found in milk, saliva, tears, and nasal secretions. LF is well known for its antibacterial and immunomodulatory effects. However, the extraction of LF from milk is inadequate for large-scale therapeutic applications, presenting a challenge for economic mass production. Recombinant protein expression systems offer a solution to overcome this challenge and efficient production of LF. This review discusses recent progress in the translational research of LF gene transfer and biopharming, focusing on different expression systems such as bacteria, yeast, filamentous fungi, transgenic crops, and animals as well as purification methods. The optimization of expression yields, prospects for genetic engineering, and biotechnology to enhance LF production for biomedical applications are emphasized. This review systematically sourced the literature from 1987 to 2025 from leading scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. Despite ongoing debates, progress in this field indicates a viable path towards the effective use of LF in therapeutic settings. Full article

Pseudomonas aeruginosa poses significant health threats due to its multidrug-resistant profile, particularly affecting immunocompromised individuals. The pathogen’s ability to produce virulence factors and antibiotic-resistant biofilms, orchestrated through quorum-sensing (QS) mechanisms, complicates conventional therapeutic interventions. This review aims to critically assess the potential of anti-QS strategies as alternatives to antibiotics against P. aeruginosa infections. Comprehensive literature searches were conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies addressing QS inhibition strategies published recently. Anti-QS strategies significantly attenuate bacterial virulence by disrupting QS-regulated genes involved in biofilm formation, motility, toxin secretion, and immune evasion. These interventions reduce the selective pressure for resistance and enhance antibiotic efficacy when used in combination therapies. Despite promising outcomes, practical application faces challenges, including specificity of inhibitors, pharmacokinetic limitations, potential cytotoxicity, and bacterial adaptability leading to resistance. Future perspectives should focus on multi-target QS inhibitors, advanced delivery systems, rigorous preclinical validations, and clinical translation frameworks. Addressing current limitations through multidisciplinary research can lead to clinically viable QS-targeted therapies, offering sustainable alternatives to traditional antibiotics and effectively managing antibiotic resistance. Full article

Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article

As direct detection methods of Borrelia burgdorferi are limited, serology plays an important role in diagnosing Lyme disease (LD). There are various types of Lyme serological tests with varying diagnostic accuracy, so it is necessary to compare and rank them. The aim of this study is to compare the accuracy of various serological diagnostic methods for LD using network meta-analysis (NMA). We searched the Cochrane Library and PubMed databases for all serological diagnostic accuracy studies published from the discovery of LD until June 2024. After screening, we assessed the quality of the included studies with QUADAS-C and extracted relevant data. We calculated the Q* index of the receiver operating characteristic curve for each diagnostic test. Meta-disc 2.0 and Stata 15.0 were used to perform traditional meta-analysis and NMA with the gold standard (the comprehensive evaluation) as a reference. We then compared the Q* index values between different methods using two-by-two comparisons and ranked them accordingly. A total of 52 studies with 181,032 participants, including 5318 patients with LD, were included. These studies covered 14 diagnostic methods. The results of the NMA suggest that modified two-tiered testing (MTTT), C6 enzyme immunoassay (EIA), and standard two-tiered testing (STTT) rank in the top three among the 14 methods in terms of Q* index, with MTTT being the highest, followed by C6 EIA and STTT. MTTT and C6 EIA have higher overall diagnostic performance, and their accuracy is not inferior to that of the widely used STTT (PROSPERO CRD42022378326). Full article

Background: Tranexamic acid is an antifibrinolytic medication often used to prevent hemorrhage. The dosage and route of administration can vary depending on specialty and indication, although one of the most common routes includes intravenous application. Other possible administration modalities include intramuscular and topical applications or irrigation. Although not the most common method, more research is emerging on the topical application of the drug to prevent bleeding. Methods: Specific search terms regarding the topical administration of tranexamic acid were input into PubMed and were reviewed via Covidence. Selected studies were stratified based on specialty (ears, nose, and throat; cardiology; plastic surgery; and orthopedics), and hematologic outcomes regarding tranexamic acid use were reviewed. Results: An evaluation of the studies demonstrated the feasibility of tranexamic acid in the topical form; however, it can depend on the specialty-specific indications. Each field utilizes unique procedures or surgeries, which can play a role in the effectiveness of the medication. Conclusions: While the current literature demonstrates the feasibility of tranexamic acid, further research is needed to understand its viability in other fields, such as obstetrics. Full article

The increase in the elderly population globally reflects a change in the population’s mindset regarding preventive health measures and necessitates a rethinking of healthcare strategies. The integration of machine learning (ML)-type algorithms in geriatrics represents a direction for optimizing prevention, diagnosis, prediction, monitoring, and treatment. This paper presents a systematic review of the scientific literature published between 1 January 2020 and 31 May 2025. The paper is based on the applicability of ML techniques in the field of geriatrics. The study is conducted using the Web of Science database for a detailed discussion. The most studied algorithms in research articles are Random Forest, Extreme Gradient Boosting, and support vector machines. They are preferred due to their performance in processing incomplete clinical data. The performance metrics reported in the analyzed papers include the accuracy, sensitivity, F1-score, and Area under the Receiver Operating Characteristic Curve. Nine search categories are investigated through four databases: WOS, PubMed, Scopus, and IEEE. A comparative analysis shows that the field of geriatrics, through an ML approach in the context of elderly nutrition, is insufficiently explored, as evidenced by the 61 articles analyzed from the four databases. The analysis highlights gaps regarding the explainability of the models used, the transparency of cross-sectional datasets, and the validity of the data in real clinical contexts. The paper highlights the potential of ML models in transforming geriatrics within the context of personalized predictive care and outlines a series of future research directions, recommending the development of standardized databases, the integration of algorithmic explanations, the promotion of interdisciplinary collaborations, and the implementation of ethical norms of artificial intelligence in geriatric medical practice. Full article

Background/Objectives: The aim of this systematic review was to compare the effectiveness of virtual reality (VR)-based training with conventional exercise programs in improving functional outcomes related to fall risk among older adults with various health conditions. Methods: The review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO (registration number CRD42022345678). The databases Scopus, PubMed, Web of Science, and EBSCO were searched up to 31 March 2025. Randomized controlled trials (RCTs) were included if they involved participants aged ≥60 years, a VR intervention lasting ≥6 weeks, and a control group performing traditional exercises or receiving usual care. Methodological quality was assessed using the PEDro scale, and a narrative synthesis was performed across four outcome domains: balance, mobility, cognitive function, and fall risk. Results: Seven RCTs were included in the analysis (totaling 664 participants). VR training was found to be at least as effective as conventional exercise in improving balance (e.g., Berg Balance Scale) and mobility (e.g., Timed Up and Go), with some studies showing superior effects of VR. One RCT demonstrated that combining VR with balance exercises (MIX) yielded the greatest improvements in muscle strength and physical performance. Additionally, two studies reported cognitive benefits (e.g., MoCA) and a 42% reduction in fall incidence within six months following VR intervention. The methodological quality of the included studies was moderate to high (PEDro score 5–9/10). Conclusions: VR-based training represents a safe and engaging supplement to geriatric rehabilitation, effectively improving balance, mobility, and, in selected cases, cognitive function, while also reducing fall risk. Full article

Background: Hip fractures represent a major clinical challenge, particularly in elderly and frail patients, where postoperative pain control must balance effective analgesia with motor preservation to facilitate early mobilization. Various regional anesthesia techniques are used in this setting, including the pericapsular nerve group (PENG) block, fascia iliaca compartment block (FICB), femoral nerve block (FNB), and quadratus lumborum block (QLB), yet optimal strategies remain debated. Objectives: To systematically review the efficacy, safety, and clinical applicability of major regional anesthesia techniques for pain management in hip fractures, including considerations of fracture type, surgical approach, and functional outcomes. Methods: A systematic literature search was conducted following PRISMA 2020 guidelines in PubMed, Scopus, Web of Science, and the virtual library of the Hospital Central de la Defensa “Gómez Ulla” up to March 2025. Inclusion criteria were RCTs, systematic reviews, and meta-analyses evaluating regional anesthesia for hip surgery in adults. Risk of bias in RCTs was assessed using RoB 2.0, and certainty of evidence was evaluated using the GRADE approach. Results: Twenty-nine studies were included, comprising RCTs, systematic reviews, and meta-analyses. PENG block demonstrated superior motor preservation and reduced opioid consumption compared to FICB and FNB, particularly in intracapsular fractures and anterior surgical approaches. FICB and combination strategies (PENG+LFCN or sciatic block) may provide broader analgesic coverage in extracapsular fractures or posterior approaches. The overall risk of bias across RCTs was predominantly low, and certainty of evidence ranged from moderate to high for key outcomes. No significant safety concerns were identified across techniques, although reporting of adverse events was inconsistent. Conclusions: PENG block appears to offer a favorable balance of analgesia and motor preservation in hip fracture surgery, particularly for intracapsular fractures. For extracapsular fractures or posterior approaches, combination strategies may enhance analgesic coverage. Selection of block technique should be tailored to fracture type, surgical approach, and patient-specific functional goals. Full article

Neuromuscular hip dysplasia (NHD) is a common deformity in children with cerebral palsy (CP). Although some predictive factors of NHD are known, the prediction of NHD is in its infancy. We present a Clinical Decision Support System (CDSS) designed to calculate the probability of developing NHD in children with CP. The system utilizes an ensemble of three machine learning (ML) algorithms: Neural Network (NN), Support Vector Machine (SVM), and Logistic Regression (LR). The development and evaluation of the CDSS followed the DECIDE-AI guidelines for AI-driven clinical decision support tools. The ensemble was trained on a data series from 182 subjects. Inclusion criteria were age between 12 and 18 years and diagnosis of CP from two specialized units. Clinical and functional data were collected prospectively between 2005 and 2023, and then analyzed in a cross-sectional study. Accuracy and area under the receiver operating characteristic (AUROC) were calculated for each method. Best logistic regression scores highlighted history of previous orthopedic surgery (p = 0.001), poor motor function (p = 0.004), truncal tone disorder (p = 0.008), scoliosis (p = 0.031), number of affected limbs (p = 0.05), and epilepsy (p = 0.05) as predictors of NHD. Both accuracy and AUROC were highest for NN, 83.7% and 0.92, respectively. The novelty of this study lies in the development of an efficient Clinical Decision Support System (CDSS) prototype, specifically designed to predict future outcomes of neuromuscular hip dysplasia (NHD) in patients with cerebral palsy (CP) using clinical data. The proposed system, PredictMed-CDSS, demonstrated strong predictive performance for estimating the probability of NHD development in children with CP, with the highest accuracy achieved using neural networks (NN). PredictMed-CDSS has the potential to assist clinicians in anticipating the need for early interventions and preventive strategies in the management of NHD among CP patients. Full article

Despite the extensive evidence supporting the effectiveness of cognitive stimulation, differences in results may be due to the influence of cognitive and non-cognitive aspects in people with dementia. The aim of this systematic review is to identify the most reliable variables in forecasting the effectiveness of cognitive stimulation in people with mild to moderate dementia. According to PRISMA guidelines, the research was conducted using five databases (PubMed, Scopus, Cochrane, Web of Science, APA PsycInfo), considering randomized controlled trials. A total of six studies were included. Different aspects moderating the gain resulting from cognitive intervention were collected and assessed in terms of demographic, cognitive, emotional, social, and quality of life parameters. People with dementia benefit more from cognitive intervention if they are female, if they have a low formal education level, a low baseline level of cognitive function, and lower depressive symptoms, and if caregivers actively participate in sessions. Quality of life, if low at baseline, also seems to improve following CST intervention. A deeper understanding of the cognitive and non-cognitive aspects ensuring improvement after cognitive stimulation may guide future research to develop more personalized interventions. Full article

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article

The emergence and spread of HIV drug resistance mutations (DRMs) pose a threat to current and future treatment options. To inform policy, this review aimed to determine the magnitude and patterns of DRMs in patients on ART in Tanzania. A systematic literature search was conducted in MEDLINE through PubMed, Embase, and CINAHL up to December 2024. A total of 9685 HIV patients from 23 eligible studies were analyzed. The prevalence of virological failure in studies that used a threshold of >1000 and >400 copies/mL was 24.83% (95% CI: 17.85–32.53%) and 36.94% (95% CI: 24.79–50.00%), respectively. Major DRMs were observed at 87.61% (95% CI: 76.25–95.91%). A decrease in prevalence was observed in studies conducted from 2019, with a pooled prevalence of 62.15% (95% CI: 31.57–88.33%). The most frequently observed HIV-1 subtypes were subtype C at 36.20% (95% CI: 30.71–41.85%), A1 at 33.13% (95% CI: 28.23–38.20%), and subtype D at 16.00% (95% CI: 11.41–21.12%), while recombinant forms of the virus were observed at 13.29% (95% CI: 9.79–17.17%). The prevalence of DRMs against NRTIs and NNRTIs was significantly high, while that against INSTIs and PIs was low, supporting the continued use of PI- and INSTI-based regimens in Tanzania and the need for continued surveillance of DRMs. Full article

Background: Reverse total shoulder arthroplasty (RTSA) is increasingly used for managing cuff tear arthropathy, osteoarthritis, complex fractures, and revision procedures. As the demand for surgical precision and reproducibility grows, immersive technologies such as virtual reality (VR), augmented reality (AR), and metaverse-based platforms are being explored for surgical training, intraoperative guidance, and rehabilitation. While early data suggest potential benefits, a focused synthesis specific to RTSA is lacking. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search of PubMed, Scopus, and Cochrane Library databases was performed through 30 May 2025. Eligible studies included those evaluating immersive technologies in the context of RTSA for skill acquisition or intraoperative guidance. Only peer-reviewed articles published in English were included. Data were synthesized narratively due to heterogeneity in study design and outcome metrics. Results: Out of 628 records screened, 21 studies met the inclusion criteria. Five studies evaluated immersive VR for surgical training: four randomized controlled trials and one retrospective case series. VR training improved procedural efficiency and showed non-inferiority to cadaveric training. Sixteen studies investigated intraoperative navigation or AR guidance. Clinical and cadaveric studies consistently reported improved accuracy in glenoid baseplate positioning with reduced angular and linear deviations in postoperative controls as compared to preoperative planning. Conclusions: Immersive technologies show promise in enhancing training, intraoperative accuracy, and procedural consistency in RTSA. VR and AR platforms may support standardized surgical education and precision-based practice, but their broad clinical impact remains limited by small sample sizes, heterogeneous methodologies, and limited long-term outcomes. Further multicenter trials with standardized endpoints and cost-effectiveness analyses are warranted. Postoperative rehabilitation using immersive technologies in RTSA remains underexplored and presents an opportunity for future research. Full article

The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, its role in R-PDAC is less clearly defined. Additionally, the role of immunotherapy in PDAC is still being explored, with ongoing trials investigating new combinations to overcome the tumor’s immune-resistant microenvironment. This article provides a comprehensive narrative review of the current evidence comparing NAT with upfront surgery in pancreatic cancer management, focusing on randomized controlled trials and meta-analyses that assess outcomes in R-PDAC and BR-PDAC. The review aims to determine whether NAT offers a significant survival advantage over traditional post-operative strategies and to clarify which clinical scenarios may benefit most from NAT. The literature was identified through a systematic search of PubMed, Scopus, and Google Scholar databases up to March 2025. Article selection adhered to the PRISMA guidelines. Our review of existing evidence supports NAT as the standard of care for BR-PDAC. Meanwhile, management of R-PDAC should be tailored individually, guided by risk stratification that considers both clinical parameters and molecular features. Immunotherapy and targeted therapies are still in early research phases, and their further integration as NAT remains controversial. Full article

Cefepime-enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination showing good activity against multidrug-resistant (MDR) Gram-negative bacteria producing a variety of β-lactamases. In this systematic review, we aimed to evaluate the available data on resistance to this drug. We performed a thorough search of four databases (Embase, PubMed, Scopus, and Web of Science), as well as backward citation searching, to identify studies containing data on resistance to cefepime-enmetazobactam. The data were extracted and analyzed according to the breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA), or the specific breakpoints reported by the authors of the respective studies. Analysis based on the type of lactamases produced by the isolates was also performed. Ten studies reported in vitro susceptibility testing and mechanisms of antimicrobial resistance. The total number of isolates was 15,408. The activity of cefepime-enmetazobactam against β-lactamase-producing isolates was variable. The resistance of the studied extended-spectrum β-lactamase (ESBL)-producing and ampicillin C β-lactamase (AmpC)-producing isolates was low (0–2.8% and 0%, respectively). The resistance was higher among oxacillinase-48 β-lactamase (OXA-48)-producing and Klebsiella pneumoniae carbapenemase (KPC)-producing isolates (3.4–13.2% and 36.7–57.8%, respectively). High resistance was noted among metallo-β-^lactamase (MBL)-producing isolates (reaching 87.5% in one study), especially those producing New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM), which had the highest rates of resistance. The high activity of cefepime-enmetazobactam against Enterobacterales and selected lactose non-fermenting Gram-negative pathogens, including ESBL-producing and AmpC-producing isolates, makes it a potential carbapenem-sparing agent. The drug should be used after in vitro antimicrobial susceptibility testing in patients with infections caused by OXA-48, KPC, and MBL-producing isolates. Full article