Search Results (2,830)

Inhaled dry powder formulations of antiviral agents represent a novel and potentially transformative approach to managing respiratory viral infections. Traditional antiviral therapies in the form of tablets or capsules often face limitations in terms of therapeutic activity, systemic side effects, and delayed onset of action. Dry powder inhalers (DPIs) provide a targeted delivery system, ensuring the direct administration of antivirals to the infection site, the respiratory tract, which potentially enhance therapeutic efficacy and minimize systemic exposure. This review explores the current state of inhaled dry powder antiviral agents, their advantages over traditional routes, and specific formulations under development. We discuss the benefits of targeted delivery, such as improved drug deposition in the lungs and reduced side effects, alongside considerations related to the formulation preparation. In addition, we summarize the developed (published and marketed) inhaled dry powders of antiviral agents. Full article

Poor water solubility remains a significant challenge in the pharmaceutical industry that limits the therapeutic efficacy and bioavailability of many active pharmaceuticals. Soluplus^® (SLP), an amphiphilic graft copolymer made of polyethylene glycol, polyvinyl caprolactam, and polyvinyl acetate, has been gaining interest in recent years as it addresses these limitations by acting as a versatile carrier. Its ability to form stable amorphous dispersions and enhance drug solubility, as well as its physicochemical properties, support its role as a key excipient in advanced drug delivery systems. Recent investigations have demonstrated the adaptability of SLP in addressing drug delivery requirements, offering controlled release, improved targeting, and superior therapeutic outcomes. This review examines some key formulation methods that make use of SLP, including hot-melt extrusion, spray drying, electrospinning, drug–polymer layering, and capsule and tablet formulations, highlighting the capacity of SLP to overcome formulation challenges. Biomedical applications of SLP have also been explored, with a focus on its role in improving the delivery of antitumoral, anti-inflammatory, antimicrobial, and antiparasitic drugs. Full article

This study investigated the flowering physiology of Minuartia laricina (L.) Mattf. to provide fundamental information for the development of flowering control techniques. A phenology test was conducted in an open field, where M. laricina overwintered from December to February. Flower buds began to form in late March as temperatures and photoperiods increased. Flowering started in late April and continued until mid-June, with seeds maturing in capsule-shaped fruits by mid-August. In a greenhouse experiment, M. laricina was subjected to cold treatments at 5 °C for 0, 2, 4, 8, or 12 weeks, followed by photoperiod treatments of 9/15, 11/13, 13/11, 16/8, 24/0 h day/night photoperiod, or night interruption (9 h + 4 h). Plant growth and flowering were measured during the photoperiod treatments. The results showed 100% flowering with 8 weeks of cold treatment and under 16 h or longer photoperiod conditions. However, without cold treatments flowering was not observed across all photoperiods. These findings align with outdoor conditions, where M. laricina flowers experience a cold winter and under long photoperiods. Thus, M. laricina is classified as an obligate vernalization and long-day plant, requiring at least eight weeks of cold and a 16/8 h photoperiod to flower. Full article

This study evaluates the potential of ChatGPT as a tool for providing information to patients with frozen shoulder, focusing on its validity, utility, and safety. Five experienced physicians selected fourteen key questions on musculoskeletal disorders after discussion and verified their adequacy by consulting one hundred and twenty frozen shoulder patients for additional or alternative inquiries. These questions were input into ChatGPT version 4.0, and its responses were assessed by the physicians using a 5-point Likert scale, with scores ranging from 1 (least favorable) to 5 (most favorable) in terms of validity, safety, and utility. The findings showed that for validity, 85.7% of the responses scored 5, and 14.3% scored 4. For safety, 92.9% received a score of 5, while one response received a 4. Utility ratings also demonstrated high scores, with 85.7% of responses rated 5 and 14.3% rated 4. These results indicate that ChatGPT provides generally valid, safe, and useful information for patients with frozen shoulder. However, users should be aware of potential gaps or inaccuracies, and continued updates are necessary to ensure reliable and accurate guidance. It should not be considered a substitute for professional medical advice, diagnosis, or treatment, highlighting the need for continued updates to ensure reliable and accurate guidance. Full article

Celiac disease and gluten sensitivity affect a significant portion of the population and require adherence to a gluten-free diet. Dining in social settings, such as family events, workplace gatherings, or restaurants, makes it difficult to ensure that certain foods are gluten-free. Despite the availability of portable gluten testing devices, these instruments have high costs, disposable capsules, depend on user preparation and technique, and cannot analyze an entire meal or detect gluten levels below the legal thresholds, potentially leading to inaccurate results. In this study, we propose RGB (Recognition of Gluten in Bread), a novel deep learning-based method for automatically detecting gluten in bread images. RGB is a decision-support tool to help individuals with celiac disease make informed dietary choices. To develop this method, we curated and annotated three unique datasets of bread images collected from Pinterest, Instagram, and a custom dataset containing information about flour types. Fine-tuning pre-trained convolutional neural networks (CNNs) on the Pinterest dataset, our best-performing model, ResNet50V2, achieved 77% accuracy and recall. Transfer learning was subsequently applied to adapt the model to the Instagram dataset, resulting in 78% accuracy and 77% recall. Finally, further fine-tuning the model on a significantly different dataset, the custom bread dataset, significantly improved the performance, achieving an accuracy of 86%, precision of 87%, recall of 86%, and F1-score of 86%. Our analysis further revealed that the model performed better on gluten-free flours, achieving higher accuracy scores for these types. This study demonstrates the feasibility of image-based gluten detection in bread and highlights its potential to provide a cost-effective non-invasive alternative to traditional testing methods by allowing individuals with celiac disease to receive immediate feedback on potential gluten content in their meals through simple food photography. Full article

Lyophilized organ extracts from livestock such as beef or elk are widely commercially proposed as animal-sourced nutraceuticals. Such preparations contain blends of vitamins and nutrients that may be employed for general or specific dietary supplementation. The first objective of this study was to develop an optimized and function-oriented manufacturing process for stabilized organ-specific extracts of American buffalo (Bison bison). The second objective of the study was to perform functional benchmarking of the obtained stabilized extracts by focusing on antioxidant attributes, which are key properties of nutraceuticals. Methodologically, a two-step lyophilization process, hard-shell capsule formulation, and process quality control elements were adapted from pharmaceutical technology practices. Stabilized extracts (300 mg capsules) were derived from the spleen, heart, liver, kidneys, lungs, and thymus of grass-fed and grass-finished American bison (born and raised in a tempered climate in Geneva, Switzerland). Functional benchmarking of the obtained extracts was performed using orthogonal methods of antioxidant activity determination (TEAC, FRAP, and H₂O₂ challenge assays). Firstly, the developed biomass transformation process enabled the considered organs to be effectively stabilized while reaching the desired quality attributes. Secondly, functional characterization of the formulated extracts revealed significant and organ-specific antioxidant attributes, wherein liver-derived materials were found to be the most potent. Thirdly, key quality and functional parameters (residual moisture levels and TEAC) were found to be stable over 12 months of storage following extract preparation. Overall, the present study provides an evidence-based technical/functional rationale for the preparation and control of American bison organ-specific lyophilized extracts to be included in nutraceutical preparations. Full article

Conventional drug delivery approaches, including tablets and capsules, often suffer from reduced therapeutic effectiveness, largely attributed to inadequate bioavailability and difficulties in ensuring patient adherence. These challenges have driven the development of advanced drug delivery systems (DDS), with hydrogels and especially nanogels emerging as promising materials to overcome these limitations. Hydrogels, with their biocompatibility, high water content, and stimuli-responsive properties, provide controlled and targeted drug release. This review explores the evolution, properties, and classifications of hydrogels versus nanogels and their applications in drug delivery, detailing synthesis methods, including chemical crosslinking, physical self-assembly, and advanced techniques such as microfluidics and 3D printing. It also examines drug-loading mechanisms (e.g., physical encapsulation and electrostatic interactions) and release strategies (e.g., diffusion, stimuli-responsive, and enzyme-triggered). These gels demonstrate significant advantages in addressing the limitations of traditional DDS, offering improved drug stability, sustained release, and high specificity. Their adaptability extends to various routes of administration, including topical, oral, and injectable forms, while emerging nanogels further enhance therapeutic targeting through nanoscale precision and stimuli responsiveness. Although hydrogels and nanogels have transformative potential in personalized medicine, challenges remain in scalable manufacturing, regulatory approval, and targeted delivery. Future strategies include integrating biosensors for real-time monitoring, developing dual-stimuli-responsive systems, and optimizing surface functionalization for specificity. These advancements aim to establish hydrogels and nanogels as cornerstones of next-generation therapeutic solutions, revolutionizing drug delivery, and paving the way for innovative, patient-centered treatments. Full article

Paper has the multiple advantages of being breathable, sustainable, environmentally friendly, and non-toxic for medical care. However, the flammability stemming from the raw materials of paper has limited its use in medical heat therapy. In this paper, a composite flame-retardant coating is assembled layer by layer on a medical paper surface using medically safe natural biomaterials with starch and adenosine triphosphate as internal layers, and starch and phytic acid as external layers. With the layer-by-layer assembly using the ultrathin adsorption method, the microscopic morphology and elemental mapping reveal that all the biomaterials are deposited uniformly and have completely capsulated the paper surface fiber. The flame-retardant coating shows less impact on medical paper appearance morphology and mechanical properties in medical usability. The coated medical paper exhibits significant flame-retardant performance, such that the limiting oxygen index increases from 19.70% to 25.40% where both internal and external layers reached 100 layers (BL), and relevant residual charring in the thermogravimetric test increases 17.00 wt% in a nitrogen atmosphere and 18.00 wt% in an air atmosphere at 800 °C. The peak and total heat release rates of 100 BL medical paper reduced by approximately 91.10% and 53.10%, respectively, and the variations in both CO and CO₂ production also suggest that flame-retardant coating could effectively inhibit combustion. Benefiting from the intumescent flame-retardant function of different biomaterial combinations and the multilayer design on different thermal response temperatures, the flame retardancy of medical paper significantly improved, and this advancement will make medical heat therapy safer and healthier for patients. Full article

Background and Clinical Significance: Ectopic variceal bleeding is a rare, but regrettably life-threatening, complication of hepatic cirrhosis. There is no standardized approach to this life-threatening event due to the absence of randomized controlled trials. Prompt identification of the bleeding site is crucial for timely hemostasis using endoscopic, radiologic or surgical methods. Case presentation: Throughout this paper, we present the case of a 52-year-old patient with decompensated alcoholic cirrhosis, who was admitted for melena. Upper and lower endoscopy failed to identify the source of bleeding. Ultimately, an evaluation with endoscopic capsule identified ileal varices. The patient was referred to surgery and the outcome was successful. We approached the diagnostic and therapeutic arsenals in managing ectopic varices. Conclusions: Although ectopic variceal bleeding has a substantial potential for fatal outcomes, prompt intervention in a multidisciplinary team could be the key for patient salvation. Full article

The booming expansion of nanotechnology poses the problem of environmental pollution by nanoparticles (NPs). The available methods for sensing and removing NPs from the environment are typically lengthy and instrumentally demanding. The recent introduction of NP-imprinted polymers (NPIPs), either as films or bulk materials, is an important step toward the simple and fast sensing and removal of NPs from water and air. Similarly to the well-established molecularly imprinted polymers, in NPIPs, an organic or inorganic polymeric material is first obtained with embedded NPs. Then, the NPs are chemically or physically removed by acting as a template, i.e., leaving a polymeric matrix with cavities of the same shape and dimensions. After the first examples were published in 2014, the literature has so far reported an increasing number of NPIPs that are capable of reuptaking NPs from water (or, more rarely, air), with remarkable size and shape selectivity. By laying an NPIP layer on a reporter (typically an electrode), devices are obtained that are capable of sensing NPs. On the other hand, bulk NPIPs can reuptake massive amounts of NPs and have been used for the quantitative removal of NPs from water. This review begins with an overview of NP-imprinted hollow capsules, which can be considered the ancestors of NPIPs, both as conception and as preparative methods. Then, the literature on NPIPs is reviewed. Finally, the possible evolutions of NPIPs are highlighted from the perspective of stepping toward their real-life, field use. Full article

Pulmonary drug delivery presents a promising approach for managing respiratory diseases, enabling localized drug deposition and minimizing systemic side effects. Building upon previous research, this study investigates the cytotoxicity, permeability, and stability of a novel carrier-free dry powder inhaler (DPI) formulation comprising nanosized ketoprofen (KTP) and mannitol (MNT). The formulation was prepared using wet media milling to produce KTP-nanosuspensions, followed by spray drying to achieve combined powders suitable for inhalation. Cell viability and permeability were conducted in both alveolar (A549) and bronchial (CFBE) models. Stability was assessed after storage in hydroxypropyl methylcellulose (HPMC) capsules under stress conditions (40 °C, 75% RH), as per ICH guidelines. KTP showed good penetration through both models, with lower permeability through the CFBE barrier. The MNT-containing sample (F1) increased permeability by 1.4-fold in A549. All formulations had no effect on cell barrier integrity or viability after the impedance test, confirming their safety. During stability assessment, the particle size remained consistent, and the partially amorphous state of KTP was retained over time. However, moisture absorption induced surface roughening and partial agglomeration, leading to reduced fine particle fraction (FPF) and emitted fraction (EF). Despite these changes, the mass median aerodynamic diameter (MMAD) remained stable, confirming the formulation’s continued applicability for pulmonary delivery. Future research should focus on optimizing excipient content, alternative capsule materials, and storage conditions to mitigate moisture-related issues. Hence, the findings demonstrate that the developed ketoprofen–mannitol DPI retains its quality and performance characteristics over an extended period, making it a viable option for pulmonary drug delivery. Full article

Background: The purpose of this study was to detect proteomic alterations and corresponding signaling pathways involved in the formation of age-related cataract (ARC), diabetic cataract (DC), and post-vitrectomy cataract (PVC). Methods: Three sample types, the aqueous humor (AH), the anterior capsule (AC), and the content of the phaco cassette, were collected during phacoemulsification surgery. The samples were obtained from 12 participants without diabetes mellitus (DM), 11 participants with DM, and 7 participants without DM, with a history of vitrectomy surgery in the past 12 months. The Sp3 protocol (Single-Pot, Solid-Phase, Sample-Preparation) was used for the sample preparation. The recognition and quantification of proteins were carried out with liquid chromatography online with tandem mass spectrometry. The DIA-NN software was applied for the identification and quantification of peptides/proteins. Statistical analysis and data visualization were conducted on Perseus software. Data are available via ProteomeXchange. Results: A very rich atlas of the lens and AH proteome has been generated. Glycosaminoglycan biosynthesis and the non-canonical Wnt receptor signaling pathway were differentially expressed in ARC compared to both the DC and PVC groups. In the PVC group, complement activation was differentially expressed in AH samples, while glutathione metabolism and oxidoreductase activity were differentially expressed in AC samples. Microfilament motor activity, microtubule cytoskeleton organization, and microtubule binding were differentially expressed in the DC and PVC groups in both AH and AC samples. Conclusions: The results of this study expand the existing knowledge on pathways involved in the pathophysiology of cataract, and suggest possible important druggable targets for slower progression or even prevention of cataract. Full article

Clinical emergent bacterial pathogens are a great threat to the global health system, chiefly Gram-negative carbapenem-resistant Enterobacterales and the Klebsiella pneumoniae species complex. Here, we present the molecular and phenotypic characterization of Klebsiella quasipneumoniae subs. similipneumoniae IEC57090 strain, belonging to ST138 and showing a multidrug resistance phenotype. The bla_NDM-7 present in one of the two resistance plasmids carried by the isolate, the antibiotic resistance genes fosA, oqxAB, and acrR, and gene mutations on porins ompK36 and ompK37, both associated with cephalosporin and carbapenem resistance, were detected. Virulence factors such as the clusters of type I and III fimbria, type IV pili genes, and genes associated with the K1 capsule, siderophore production, and multiple mobile genetic elements (MGE) were predicted. The emergence of silent pathogens in clinical environments highlights the importance of active research on new threads that may compromise the last resources of antimicrobials, such as carbapenems, specifically on mobile genetic elements containing carbapenemases in emergent pathogens, which can spread these antimicrobial resistance elements. This study reinforces that molecular biology vigilance can prevent outbreaks and help to better understand antimicrobial resistance and pathogens in clinical environment dynamics. Full article

Background/Objectives: Irritable Bowel Syndrome (IBS) is a disorder of the gut-brain axis for which the gastroenterologist is most often consulted. Gastrointestinal symptoms and decreased quality of life lead to a considerable burden of disease. The exact causes of IBS are not well understood, and no standard therapy has been established. The primary outcome of the study focused on the improvements of the IBS symptoms assessed through the validated questionnaire IBS-Severity Scoring System (IBS-SSS). Similarly, secondary outcomes geared towards the improvement of the quality of life (IBS-Quality of Life (IBS-QoL) and the Gastrointestinal Quality of Life Index (GIQLI)) and specific IBS symptoms (bloating, abdominal distension, feeling of heaviness, abdominal pain, and flatulence), were assessed through self-administered questionnaires. Intestinal habits (consistency and frequency of depositions) through subject stratification into diarrhoea (IBS-D), constipation (IBS-C), mixed type (IBS-M), as well as the treatment tolerability were also evaluated. Methods: A randomised, placebo-controlled, double-blind, clinical trial was conducted on 156 enrolled IBS patients (79 female and 77 male), aged 18–70 years, randomised (1:1 allocation ratio) to receive either two capsules per day of the food supplement (containing 480 mg of a complex of tannin extracts) or a placebo for 56 days. Linear random intercept mixed models (LMM) were used to analyse all experimental variables Results: Supplementation resulted in a significant improvement (p < 0.05) in the primary outcome IBSS score, with respect to the placebo group, changing the IBS condition going from mild (242.3 ± 89.8) to moderate (148.1 ± 60.6). Similarly, all indicators concerning quality of life, and specific intestinal symptoms resulted in a significant improvement (p < 0.05). Furthermore, the tannin-based treatment showed the ability to modulate the response to different symptomatology such as diarrhoea and constipation, without side effects being reported. Conclusions: The use of a supplement based on chestnut and quebracho tannins presents great application potential in the management of IBS-related disorders, with the peculiarity of resolving opposite symptoms, such as diarrhoea and constipation, indiscriminately. Full article

The aim of this study was to verify whether the expression of proteins related to the formation of invadopodia, MT1-MMP, cortactin, Tks-4 and Tks-5 is associated with the degree of tumor invasiveness of different types of unicystic ameloblastomas. An immunohistochemical study was performed on 29 unicystic ameloblastoma (UA) samples, 9 conventional ameloblastoma (CAM) samples and 9 dental follicle (DF) samples. The potential for tumor invasiveness was assessed based on the immunoexpression of the following invadopodia-forming proteins: MT1-MMP, cortactin, Tks-4 and Tks5. Mural unicystic ameloblastoma (MUA) showed higher MT1-MMP, cortactin, Tks-4, and Tks-5 immunoexpression than luminal and intra-luminal types. Conventional ameloblastoma exhibited lower MT1-MMP, cortactin, and Tks-5 expression compared to MUA. MUA’s cystic capsule neoplastic cells had significantly higher MT1-MMP, cortactin, Tks-4, and Tks-5 expression than lumen cells. Dental follicles showed minimal expression. Neoplastic cells in the cystic capsule of mural unicystic ameloblastomas showed higher invadopodia-related protein expression than lumen and luminal/intraluminal cells, suggesting that proximity to the bone region influences the aggressive behavior of mural unicystic ameloblastomas more compared to other subtypes. Full article