Odomwolfe0821

Sensitive and validated instruments are available to capture generic, dimensional, and disease-specific PROs in patients with valvular heart disease. The integration of PROs in clinical care presents significant opportunities to help guide treatment decision and monitor health status. The integration of patients' perspectives promotes the shift to patient-centred care and optimal outcomes, and contributes to transforming the way we care for patients with valvular heart disease.

There are few data on the prevalence and clinical consequences of coronary artery aneurysms (CAA) in adult patients with Marfan syndrome (MFS).

We performed a retrospective cohort study of 109 patients with pathogenic variants in the FBN1 gene. Diameters of the left main coronary artery (LMCA) and right coronary artery (RCA) were measured by computed tomography angiography.

The overall prevalence of CAA was 46%. The prevalence rates of CAA were 18% and 68% in patients with a native aortic root (group 1) and patients with previous aortic root replacement (group 2), respectively. Previous aortic dissection or aortic intervention, longer time from aortic root replacement, higher systemic score, significant mitral valve involvement, and diffuse aortic disease were correlated with CAA. During a mean follow-up of 8.5 ± 7.6 years, four patients developed pseudoaneurysms of the coronary anastomoses requiring surgery.

CAA are common in adult Marfan patients and are associated with a more severe aortic phenotype and a longer follow-up after aortic root replacement. Our study demonstrates that coronary artery size should be regularly followed, mostly after aortic root replacement and in patients with a severe aortic phenotype. Large multicentre studies are warranted to elucidate the most appropriate surveillance plan.

CAA are common in adult Marfan patients and are associated with a more severe aortic phenotype and a longer follow-up after aortic root replacement. Our study demonstrates that coronary artery size should be regularly followed, mostly after aortic root replacement and in patients with a severe aortic phenotype. Large multicentre studies are warranted to elucidate the most appropriate surveillance plan.Colorectal carcinoma is a complex malignancy and current therapies are hampered by systemic toxicity and tumor resistance to treatment. In the field of cancer therapy, copper (Cu) compounds hold great promise, with some reaching clinical trials. However, the anticancer potential of Cu complexes has not yet been fully disclosed due to speciation in biological systems, leading to inactivation and/or potential side effects. This is the case of the widely studied Cu(II) complexes featuring phenanthroline ligands, with potent antiproliferative effects in vitro, but often failing in vivo. Aiming to overcome these limitations and maximize its anticancer effects in vivo, the Cu(II) complex (Cu(1,10-phenanthroline)Cl2) (Cuphen), displaying IC50 values less then 6 μM against different tumor cell lines, was loaded in long circulating liposomes with pH-sensitive properties (F1, DMPCCHEMSDSPE-PEG; F2, DOPECHEMSDMPCDSPE-PEG). This enabled a pH-dependent Cuphen release, with F1 and F2 releasing 36/78% and 47/94% of Cuphen ting toxic side effects. F2 led to a tumor volume reduction of ca. 50%. This was confirmed by RTV analysis, where F2 reached a value of 1.3 vs 4.4 (Control), 5.8 (Phen) and 3.8 (free Cuphen). These results clearly demonstrated the important role of the Cu(II) for the observed biological activity that was maximized following the association to a lipid-based nanosystem. Overall, this study represents a step forward in the development of pH-sensitive nanotherapeutic strategies of metallodrugs for colon cancer management.Excipient concentrations are critical quality attributes of monoclonal antibody (mAb) drug products and affect their safety and efficacy. In manufacturing processes, mAb products are formulated into the buffer containing the desired excipients using ultrafiltration (UF) and diafiltration (DF). Control of excipient concentrations is a challenge during high concentration UF due to electrostatic interactions which lead to excipient concentration drifts. This challenge is of increasing importance due to the growing preference towards high concentration subcutaneous drug formulations over conventional intravenous formulations in the biotherapeutic industry. Excipient concentrations are currently measured using offline RP-HPLC which is time-consuming and not suited for real time control. We propose a novel process analytical technology (PAT) tool for monitoring and control of mAb and excipients in high concentration UF using Near Infrared Spectroscopy (NIRS). The NIRS is able to monitor concentrations within ±1% for mAb and ±2% for two common excipients, L-histidine and acetate. A Python-based controller uses real time concentration data to deliver concentrated excipient stock solutions to the UF reservoir whenever the excipient concentrations drift out of range. this website The PAT control system is able to achieve the target formulation without manual intervention or at-line analysis and is well-suited for implementation in mAb manufacturing platforms.Intracellular pathogens pose serious challenges to the public health worldwide. Lysin, peptidoglycan hydrolase from phage, is promising alternative to conventional antibiotics because of its high bactericidal activity and low risk of resistance. However, most proteinaceous lysins cannot penetrate the mammalian cell membrane because of size exclusion. Previously, we reported a broad-spectrum chimeric lysin, ClyR, with a cysteine, histidine-dependent amidohydrolase/peptidase catalytic domain from PlyC lysin and an SH-3b cell-wall binding domain from PlySs2 lysin. Herein, we further report that a novel internal cell-penetrating peptide (CPP) is predicted in the junction region of the two constitutive domains of ClyR, mediated by which ClyR can be internalized by epithelial cells through caveolin-dependent endocytosis to target intracellular pathogens. Residues K153, P154, R169, and R188 of the internal CPP were found to be essential for ClyR-mediated internalization and intracellular killing. RNA-seq analysis further showed that there are minor differences in transcript and metabolic profiles from epithelial cells exposed to 100 μg/ml ClyR for 24 h. Taken together, our findings demonstrate a novel mechanism of internalization by ClyR, providing new insights into the rational designing of the next-generation lysins to target both extracellular and intracellular pathogens.During the last decades, inkjet printing has emerged as a novel technology and attracted the attention of the pharmaceutical industry, as a potential method for manufacturing personalized and customizable dosage forms to deliver drugs. link2 Commonly, the desired drug is dissolved or dispersed within the ink and then dispensed in various dosage forms. Using this approach, several studies have been conducted to load hydrophilic or poorly water-soluble small molecules onto the surface of different solid substrates, including films, tablets, microneedles, and smart data-enriched edible pharmaceuticals, using two-dimensional and three-dimensional inkjet printing methods, with high dose accuracy and reproducibility. Furthermore, biological drugs, such as peptides, proteins, growth factors, and plasmids, have also been evaluated with positive results, eliciting the expected biological response; nonetheless, minor changes in the structure of these compounds with significant impaired activity cannot be dismissed. Another strategy using inkjet printing is to disperse drug-loaded nanoscale particles in the ink liquid, such as nanosuspension, nanocomplexes, or nanoparticles, which have been explored with promising results. Although these favorable outcomes, the proper selection of ink constituents and the inkjet printer, the correlation of printing cycles and effectively printed doses, the stability studies of drugs within the ink and the optimal analysis of samples before and after the printing process are the main challenges for inkjet printing, and therefore, this review analyzes these aspects to assess the body of current literature and help to guide future investigations on this field.Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of gastrointestinal tract with rising incidence. Established treatments of IBD are characterized by significantly adverse effects, insufficient therapeutic efficacy. Employing the oral nano-drug delivery systems for targeted therapy is capable of effectively avoiding systematic absorption and increasing local drug concentration, consequently leading to decreased adverse effects and improved therapeutic outcomes. link3 This review gives a brief profile of pathophysiological considerations in terms of developing disease-directed drug delivery systems, then focuses on mechanisms and strategies of current oral nano-drug delivery systems, including size-, enzyme-, redox-, pH-, ligand-receptor-, mucus-dependent systems, and proposes the future directions of managements for IBD.Chitosan-based biomaterials has shown great advantages in a broad range of applications, including drug delivery, clinical diagnosis, cell culture and tissue engineering. However, due to the lack of control over the fabrication processes by conventional techniques, the wide application of chitosan-based biomaterials has been hampered. Recently, microfluidics has been demonstrated as one of the most promising platforms to fabricate high-performance chitosan-based multifunctional materials with monodisperse size distribution and accurately controlled morphology and microstructures, which show great promising for biomedical applications. Here, we review recent progress of the fabrication of chitosan-based biomaterials with different structures and integrated functions by microfluidic technology. A comprehensive and in-depth depiction of critical microfluidic formation mechanism and process of various chitosan-based materials are first interpreted, with particular descriptions about the microfluidic-mediated control over the morphology and microstructures. Afterwards, recently emerging representative applications of chitosan-based multifunctional materials in various fields, are systematically summarized. Finally, the conclusions and perspectives on further advancing the microfluidic-aided chitosan-based multifunctional materials toward potential and versatile development for fundamental researches and biomedicine are proposed.The aim of this study was to prepare dissolving microneedles (DMNs) patches containing tranexamic acid (TA) for the treatment of melasma. Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) were preferred as matrix materials through the compatibility experiment. In the in vitro permeation study, the transdermal amount of TA was significantly promoted through dissolving microneedles with the cumulative release was 44.43 ± 6.55%. By comparison, the release of TA solution assisted with solid microneedles (SMNs) was merely 11.31 ± 2.30% (p less then 0.05). Pharmacokinetics study indicated the bioavailability of dissolving microneedles was more than 1.3 times compared with oral administration. In pharmacodynamics investigation, TA dissolving microneedles obviously reduced melanin deposition in the skin of melasma guinea pigs after 8 consecutive administrations. In particular, the combination of tranexamic acid and licorice extract (LIC) dissolving microneedles worked better than tranexamic acid alone. Accelerated stress conditions including high temperature, high humidity, as well as photostability were designed to prove that TA microneedles maintained good pharmaceutical stability.