Search Results (1,362)

The development of layer-by-layer polyelectrolyte microcapsules (PMCs) with defined buffer capacity (BC) is a key task for creating stable systems in biomedicine and materials science. Manganese carbonate (MnCO₃), which shares properties with CaCO₃ and the ability to form hollow structures, represents a promising alternative. However, its interaction with polyelectrolytes and its influence on BC remain insufficiently studied. This research focuses on determining the BC of PMCs templated on MnCO₃ cores under varying ionic strength (0.22–3 M NaCl) and temperature (60–90 °C), as well as comparing the results with PMCs templated on CaCO₃ and PS cores. It was found that MnCO₃-based PMCs (PMC_Mn) exhibit hybrid behavior between CaCO₃- and PS-based PMCs: the BC dynamics of PMC_Mn and CaCO₃-based PMCs (PMC_Ca) in water are identical. At different ionic strength at pH < 5, the BC of PMCMn and PS-based PMCs (PMC_PS) remains unchanged, while at pH > 8.5, the BC of PMC_Mn increases only at 3 M NaCl. The BC of PMC_Mn remains stable under heating, whereas the BC of PMC_Ca and PMC_PS decreases. These results confirm that the choice of core material dictates PMC functionality, paving the way for adaptive systems in biosensing and controlled drug delivery. Full article

Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on oxidative stress in RNASEH2-mutant AGS cells. Methods and Results: By means of flow cytometry, we found that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of Forkhead Box O3 (FOXO3), cytochrome C somatic (CYCS), and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. Conclusions: In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin treatment as a valid approach to ameliorate oxidative stress-related inflammation in AGS patients. Full article

Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs and cells that are in need. For decades, green tea catechins (GTCs) have been a case in point. Because of their low redox potential and favorable positioning of hydroxyl groups, these flavonoid representatives (namely, catechin—C, epicatechin—EC, epicatechin gallate—ECG, epigallocatechin—EGC, epigallocatechin gallate—EGCG) are among the most potent plant-derived (and not only) antioxidants. The proven anti-inflammatory, neuroprotective, antimicrobial, and anticarcinogenic properties of these phytochemicals further contribute to their favorable pharmacological profile. Doubtlessly, GTCs hold the potential to “cope” with the majority of today‘s socially significant diseases, yet their mass use in clinical practice is still limited. Several factors related to the compounds’ membrane penetrability, chemical stability, and solubility overall determine their low bioavailability. Moreover, the antioxidant-to-pro-oxidant transitioning behavior of GTCs is highly conditional and, to a certain degree, unpredictable. The nanoparticulate delivery systems represent a logical approach to overcoming one or more of these therapeutic challenges. This review particularly focuses on the lipid-based nanotechnologies known to be a leading choice when it comes to drug permeation enhancement and not drug release modification nor drug stabilization solely. It is our goal to present the privileges of encapsulating green tea catechins in either vesicular or particulate lipid carriers with respect to the increasingly popular trends of advanced phytotherapy and functional nutrition. Full article

This review critically examines the recent advancements in the development and application of electrospun molecularly imprinted polymer (MIP) nanofiber membranes for environmental remediation. Emphasizing the significance of these materials, the discussion highlights the mechanisms by which electrospun MIPs achieve high selectivity and efficiency in removing various pollutants, including dyes, heavy metals, and pharmaceutical residues such as NSAIDs and antiretroviral drugs. The synthesis methodologies are explored in detail, focusing on the choice of monomers, templates, and polymerization conditions that influence the structural and functional properties of the membranes. Characterization techniques used to assess morphology, surface area, porosity, and imprinting efficacy are also examined, providing insights into how these parameters affect adsorption performance. Furthermore, the review evaluates the performance metrics of electrospun MIPs, including adsorption capacities, selectivity, reusability, and stability in complex environmental matrices. Practical considerations, such as scalability, regeneration, and long-term operational stability, are discussed to assess their potential for real-world applications. The article concludes with an outline of future research directions, emphasizing the need for multi-template imprinting, integration with existing treatment technologies, and field-scale validation to address current limitations. Full article

Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may be utilized in the treatment of orthopedic infections. Methods: We reviewed the existing guidelines on orthopedic infections and focused on situations where antibiotic combinations are recommended or proposed optionally. We chose vitro and animal studies that provide evidence for the effectiveness of several widely recommended combinations. Results: The combinations serve multiple purposes: they provide empirical coverage while awaiting microbiological results, offer targeted treatment for difficult-to-treat infections, and facilitate oral treatment primarily for staphylococcal infections. The objectives include enhancing bacterial coverage against Gram-positive and Gram-negative bacteria, achieving synergistic effects with bactericidal agents, and reducing the risk of antibiotic resistance. The review outlines specific combinations for fracture-related infections, periprosthetic joint infections, spinal infections, and anterior cruciate ligament reconstruction infections, emphasizing the importance of tailoring antibiotic choices based on local epidemiology and patient history. The review also addresses potential drawbacks of combination therapy, such as toxicity, higher costs, and drug interactions, underscoring the complexity of managing orthopedic infections effectively. Conclusions: According to the guidelines, several different proposals are made, depending in part on the countries’ epidemiology. In a well-defined situation, various authors propose either monotherapy or a combination of antibiotics. When a combination is suggested, the choice of antibiotics is based on the expected effect: broadening the spectrum, enhancing bactericidal activity, achieving a synergistic effect, or reinforcing biofilm activity to optimize the treatment. Full article

Osteoporosis is a chronic disease associated with significant morbidity and mortality and requires long-term therapy. Efficacious and well-tolerated treatments are available, but their effect is either short-lived or lost following their discontinuation. The exception is bisphosphonates that reduce bone resorption and turnover, can be administered in regimens ranging from once-daily to once-yearly, and have been shown in randomized clinical trials to reduce the incidence of all osteoporotic fractures, but their effect persists following their discontinuation. This is due to their property of being taken-up selectively by the skeleton and being slowly released following treatment arrest. This property allows the discontinuation of bisphosphonate treatment for different periods of time, the so-called drug holiday, which reduces the risk of rare adverse events while maintaining the effect; an action particularly important for patients at very high risk of fractures for whom sequential therapy with different agents is currently advised. Thus, bisphosphonates, apart from being the treatment of choice for certain groups of patients, are also indispensable for the consolidation and maintenance of the gains of all other treatments, providing, in addition, the opportunity of temporary treatment arrest. Most patients with postmenopausal osteoporosis will, therefore, receive bisphosphonate at some stage during therapy of their disease, regardless of their initial fracture risk. Full article

Osteoporosis and sarcopenia are two aspects of the geriatric syndrome that frequently occur together and affect one another in a condition referred to as osteosarcopenia. Preventive and treatment options for osteosarcopenia exist but are mainly focused on the treatment of osteoporosis, as there is still no FDA-approved treatment for sarcopenia. Drugs for osteoporosis include antiresorptive and anabolic drugs and hormonal replacement therapies and are prescribed based on age, BMD and other patient characteristics, which, however, do not include the possible co-existence of sarcopenia. As several studies and clinical trials have shown that the pharmacological treatment of osteoporosis can also affect muscle tissue, in either a positive or negative manner, sarcopenia should be another factor affecting the choice of treatment, especially when facing equal treatment options for osteoporosis. The aim of this review was to summarize our current knowledge on the effects of FDA-approved drugs for the treatment of osteoporosis on muscle quality, mass and function. A better understanding of the effects that certain drugs have on muscle tissue might in the future help us to simultaneously at least partially also address the wasting of muscle tissue and avoid further pharmacologically induced decline. Full article

Background: The treatment options for HER2-negative metastatic breast cancer include targeted therapies, cytotoxic chemotherapies, and immunotherapy. However, limited specificity and inevitable resistance highlight the need for novel agents. Antibody–drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), represent a breakthrough by selectively delivering cytotoxic agents to tumor cells, potentially improving the therapeutic index. Despite demonstrated efficacy, ADCs present toxicity profiles similar to conventional chemotherapy, alongside unique adverse events. In clinical practice, oncologists may face scenarios where both T-DXd and SG are treatment options in HER2-negative mBC. To enable shared decision-making, it is crucial to present a comprehensive overview that includes both efficacy data and detailed toxicity profiles. Our objective was to provide a pooled and informative synthesis of toxicities from pivotal studies, including graphical representations, to support informed, patient-centered medical decisions. Methods: We reviewed safety data from phase 3 clinical trials in HER2-negative mBC: DESTINY-Breast04/DESTINY-Breast06 for T-DXd and ASCENT/TROPICS-02 for SG. Adverse event (AE) profiles, including frequency and severity, were extracted, and weighted means were calculated. Emerging ADCs such as datopotamab deruxtecan and patritumab deruxtecan were considered to contextualize future therapeutic decisions. Results: Tables, bar plots and radar plots were generated. T-DXd demonstrated high rates of nausea (69.2%), fatigue (47.2%), and neutropenia (35.6%), with 52.7% experiencing grade ≥ 3 AEs. Notably, pneumonitis occurred in 10.7%, with grade ≥ 3 in 2.6%. SG showed a distinct AE profile, with higher incidences of neutropenia (67.1%), with grade ≥ 3 in 51.3%, and diarrhea (60.8%). Conclusions: The choice between ADCs in HER2-negative metastatic BC when both T-DXd and SG are treatment options should consider toxicity profiles to optimize patient-centered treatment strategies. Tailoring ADC selection based on individual tolerance and preferences is critical for shared decision-making, and future research should focus on assessing the utility and acceptability of such clinical tools to guide treatment selection. Full article

Being one of the most aggressive primary brain tumors, glioblastoma multiforme (GBM) is known from the median survivals of just 15 months following diagnosis. Conventional treatments, including surgical resection, radiotherapy, and chemotherapy, have limited efficiency due to the invasive nature of glioma cells and the presence of a blood–brain barrier. Therefore, adjuvant therapy in the form of a localized delivery of chemotherapeutic agents is indispensable to increase the chances of patients. Among a variety of advanced drug carriers, collagen has recently emerged as an excellent choice for regional chemotherapy, mainly due to its biocompatibility, biodegradability, weak antigenicity, biomimetics, and well-known safety profile, as well as its native presence in the extracellular matrix of the central nervous system. The aim of this paper is to highlight the most recent studies describing the application of collagen as a drug carrier able to provide an extended delivery of chemotherapeutic agents directly to the GBM site, and to provide exciting opportunities for its future applications. Full article

The coexistence of heart failure (HF) and chronic obstructive pulmonary disease (COPD) presents a significant clinical challenge due to the common risk factors, overlapping symptoms, and complex pathophysiological interactions and mechanisms. This comprehensive review explores the bidirectional relationship between HF and COPD, emphasizing their combined impact on morbidity, mortality, and quality of life. Epidemiological data reveal that up to one-third of patients with HF also have COPD, complicating diagnosis and leading to suboptimal treatment strategies. We discuss the pathways through which each disease exacerbates the other, the limitations of the current staging systems, the diagnostic tools needed to differentiate cardiac from pulmonary symptoms, and the treatment choices. Therapeutic management requires careful integration of pharmacologic and non-pharmacologic strategies, with attention paid to potential drug interactions. Evidence from clinical trials confirms that beta-blockers can be safely used in patients with COPD and highlights the importance of multidisciplinary, patient-centered care models. Prevention strategies, including smoking cessation, vaccination, and patient education, play a critical role in improving outcomes. Finally, we identify key research gaps and calls for more inclusive clinical guidelines to address the needs of patients with this overlapping syndrome. A coordinated, evidence-based approach is essential for optimizing care and improving the quality of life of patients facing the dual burden of HF and COPD. Full article

Background/Objectives: Hepatic clearance is important in determining clinical drug administration strategies. Achieving accurate hepatic clearance predictions through in vitro-to-in vivo extrapolation (IVIVE) relies on appropriate model selection, which is a critical step. Although numerous models have been developed to estimate drug dosage, some may fail to predict liver drug clearance owing to inappropriate hepatic clearance models during IVIVE. To address this limitation, an in silico-based model selection approach for optimizing hepatic clearance predictions was introduced in a previous study. The current study extends this strategy by verifying the accuracy of the selected models using ex situ experimental data, particularly for drugs whose model choices are influenced by protein binding. Methods: Commonly prescribed drugs were classified according to their hepatic extraction ratios and protein-binding properties. Building on previous studies that employed multinomial logistic regression analysis for model selection, a three-phase classification method was implemented to identify five representative drugs: diazepam, diclofenac, rosuvastatin, fluoxetine, and tolbutamide. Subsequently, an isolated perfused rat liver (IPRL) system was used to evaluate the accuracy of the in silico method. Results: As the unbound fraction increased for diazepam and diclofenac, the most suitable predictive model shifted from the initially preferred well-stirred model (WSM) to the modified well-stirred model (MWSM). For rosuvastatin, the MWSM provided a more accurate prediction. These three capacity-limited, binding-sensitive drugs conformed to the outcomes predicted by the multinomial logistic regression analysis. Fluoxetine was best described by the WSM, which is consistent with its flow-limited classification. For tolbutamide, a representative capacity-limited, binding-insensitive drug, no significant differences were observed among the various models. Conclusions: These findings demonstrate the accuracy of an in silico-based model selection approach for predicting liver metabolism and highlight its potential for guiding dosage adjustments. Furthermore, the IPRL system serves as a practical tool for validating the accuracy of the results derived from this approach. Full article

Carotid stenosis is a common pathology in clinical practice and unfortunately carries a high risk of serious cerebrovascular events. The early recognition of carotid plaque and, consequently, a careful analysis by means of multimodal imaging are the necessary steps to undertake a correct management pathway, aimed at preventing or, if not possible, reducing the risk of atherogenic phenomena responsible for cerebral infarction. In particular, the presence or absence of clinical symptoms, understood as the occurrence of events such as TIAs in the last 6 months, non-disabling strokes or repeated episodes of amaurosis fugax, and the degree of carotid stenosis, are certainly the most studied parameters, and as reported by several international guidelines, can lead to the best therapeutic strategy: whether to rely on conservative medical therapy or to resort to mechanical revascularization of the carotid stenosis. According to the recommendations of the European Society of Vascular Surgery, mechanical revascularization is recommended for stenosis > 50% in symptomatic patients and stenosis > 60% in asymptomatic patients. In contrast, the latest findings on plaque vulnerability have focused attention on individual patient characteristics and clinical comorbidities that may be responsible for plaque inflammation and should therefore be taken into consideration to decide if revascularization treatment is needed even in those subjects who present stenosis with less degree than reported as critical value. Moreover, further radiological investigations are fundamental to finding the presence of entities such as plaque ulceration, plaque neo-vascularization, fibrous caps, and intraplaque lipid core that are responsible for increased vulnerability. Medical therapy involves interventions aimed at eliminating cardiovascular risk factors by administering drugs that control the comorbidities responsible for worsening carotid stenosis. Recent studies are also evaluating the effectiveness of new plaque-modifying drugs or targeted anti-inflammatory agents in reducing the risk of plaque development and complications. Revascularization therapies, on the other hand, include surgery (CEA), the endovascular technique (CAS), and a new hybrid technique (TCAR): they are all valid alternatives for the treatment of carotid stenosis, each with specific technical difficulties, but on the whole with comparable safety profiles and risk rates of postoperative complications, although some recent emergencies have focused attention on possible short- and long-term gender-dependent outcome differences. The aim of this manuscript is to present the state of the art in the management of patients with carotid stenosis and to take a closer look at revascularization options. In our opinion, the choice of one strategy over another should therefore depend on gender, anatomical features of the patient, preoperative comorbidities, and last but not least, the experience of the center and the multidisciplinary team involved in the management of the patient. Full article

Background: Fever and pain are among the most frequent symptoms in pediatric care, requiring timely and appropriate management. While evidence-based guidelines are available, adherence in real-world practice remains variable. This study aimed to explore the attitudes and prescribing behaviors of Italian Primary Care Pediatricians (PCPs) in the management of fever and pain, and to assess their alignment with current clinical recommendations. Materials and Methods: An anonymous, cross-sectional survey consisting of 30 multiple-choice questions was administered to 900 PCPs between 1 July and 30 October 2024. The questionnaire assessed therapeutic preferences, dosing strategies, and perceived knowledge gaps. Invitations were distributed via pediatric scientific societies and regional professional networks. Results: A total of 244 PCPs completed the survey (response rate 27.1%). The majority were aged over 55 years (72.1%), worked in urban settings (71.3%), and had more than 20 years of clinical experience (74.6%). Most respondents (77%) reported managing pediatric fever or pain on a daily basis. Paracetamol was the preferred first-line treatment for fever (95.9%), primarily due to its perceived safety (82.4%). Ibuprofen was favored by 51.6% of those who selected it for its greater effectiveness. The alternating use of paracetamol and ibuprofen for fever was never adopted by 49.6%, while 31.6% employed this strategy, believing it to be more effective. For pain, 67.6% used paracetamol and 26.2% used ibuprofen as first-line treatments; 15.2% reported alternating the two drugs. Correct dosage practices were followed by 63.9% for both medications, although 40.2% did not differentiate dosages between fever and pain management. Conclusions: While general trends showed alignment with current guidelines, notable inconsistencies were observed in drug selection, dosage, and the use of alternating therapies. These findings highlight a pressing need to improve the dissemination and implementation of pediatric fever and pain management guidelines among PCPs in order to reduce unsafe practices, avoid therapeutic errors, and prevent unnecessary strain on emergency care services. Full article

Cell membranes are vital for living organisms and serve as a dynamic barrier between the internal and external environments. They are composed of a complex lipid bilayer embedded with proteins, allowing them to perform multiple functions like maintaining the cell structure, regulating which substances enter or leave the cell, and intercellular communication. Cellular functions are inherently linked to their membrane properties, and the heterogeneous nature of cell membranes makes the study of their physico-chemical properties extremely challenging. This review is intended to provide a comprehensive overview of the composition and physical features of the cell membrane, by focusing on the lipid and protein composition, and on the physical properties (like membrane stiffness or fluidity), highlighting how these characteristics influence cell functions. An insight into the similarities and differences from the membranes of extracellular vesicles (naturally secreted by almost all cell types) is also provided. The understanding of the physico-chemical properties of cell membranes might find application in different therapeutic fields, like disease diagnosis and development of novel drug delivery systems. Therefore, an overview of the literature works describing the rational design of biomimetic drug delivery systems is presented, focusing on the choice of lipid components, frequently inspired by the study of the composition of naturally secreted exosomes, and on the physical characterization of the systems. In the future, in-depth study of biologic vesicles might lead to the development of promising formulation for drug delivery, possibly enhancing the therapeutic outcomes of many pathologies, like cancer. Full article

Background/Objective: Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with a significant impact on quality of life and is frequently associated, from a pathogenetic perspective, with type 2 inflammation. The introduction of biologic therapies has marked a turning point in the management of severe forms of the disease, offering a valuable treatment option. However, selecting the most suitable biologic agent for a specific patient remains a clinical challenge. Artificial intelligence, and, in particular, ChatGPT, has recently been proposed as a potential tool to support medical decision-making and guide therapeutic choices. To evaluate the concordance between the therapeutic recommendations provided by ChatGPT and those of a multidisciplinary expert board in selecting the most appropriate biologic therapy for CRSwNP patients, based on the analysis of their phenotype and endotype. Methods: A multicenter observational cohort study was conducted. Clinical data from 286 patients with CRSwNP were analyzed. For each case, the therapeutic choice among Dupilumab, Mepolizumab, and Omalizumab was compared between the board and ChatGPT. Concordance rates and Cohen’s Kappa coefficient were calculated. Results: Overall concordance was 59.2%, with a Cohen’s Kappa coefficient of 0.116. Concordance by drug was 62.8% for Dupilumab, 26.5% for Mepolizumab, and 9.1% for Omalizumab. Patients presented with severe clinical profiles, with an average Nasal Polyp Score of 6.22 and an average SNOT-22 score of 64.5. Conclusions: This study demonstrates that, despite its substantial theoretical potential, ChatGPT is currently not a reliable tool for the autonomous selection of biological therapies in patients with CRSwNP. Further studies are necessary to enhance its reliability and integration into clinical practice. Full article