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Pediatric cystic fibrosis (CF) patients possess unique pharmacokinetics and may benefit from prolonged beta-lactam infusions to optimize pharmacodynamics. This study compared adverse drug event (ADE) rates with cefepime prolonged (PI) and standard infusions (SI).

This retrospective study included pediatric patients treated with cefepime for CF exacerbations between 2009 and 2019. One encounter per patient was analyzed with prioritization of SI encounters given sample size limitations. Baseline lab abnormalities, seizure disorders, and bleeding were exclusion criteria. The primary outcome was a composite safety endpoint (acute kidney injury [AKI], hepatotoxicity, hematologic toxicity, neurotoxicity, and hypersensitivity).

Of 188 patients, 135 received PI and 53 received SI. Baseline characteristics were similar between groups. More PI patients used CF transmembrane conductance regulator (CFTR) modulators (25% vs. 0%, p < 0.01) or had antibiotic allergies (62% vs. 38%, p = 0.02). Difference in rates ofics.Regenerative medicine aims to provide solutions for structural and functional recovery in conditions where organs suffer from varying degrees of diseases or injuries. However, the exogenous inflammation triggered by implanted biomaterials and endogenous inflammation caused by some disease or tissue destruction has not been solved properly yet. Herein, a functional "inner-outer" medicated core-shell electrospun fibrous membrane is fabricated with RGD surface modification for exogenous inflammation suppression and puerarin loading in the core for long-term endogenous inflammation inhibition through microsol electrospinning technique. The "outer" RGD significantly increases biocompatibility of fibrous membrane through promoting cell viability, adhesion, and proliferation while the "inner" puerarin suppresses inflammatory gene expression via sustained drug release in vitro. Moreover, in a rat abdominal wall hernia model, the functional fibrous membrane successfully reduces exogenous and endogenous inflammation response and promotes wound healing through collagen deposition, smooth muscle formation, and vascularization. In summary, the functional "inner-outer" medicated fibrous membrane holds a great potential for clinical treatment of diseases that needs tissue reconstruction structurally and functionally accompanied by immunoregulation.

The study objective was to assess the efficacy of simulators in improving the competence of students in performing a knee and shoulder arthrocentesis on cadavers and to determine the minimum number of simulator training procedures needed to achieve competence in arthrocentesis.

Two groups of 15 medical students were each trained to perform a single joint arthrocentesis ("knee group" and "shoulder group") on a simulator to serve as a control for the other. The two groups received the same theoretical training (anatomy, arthrocentesis techniques, ultrasound, and hybrid simulation). Each student punctured the two joints on a cadaver. A student was considered "competent on the cadaver" if they succeeded at two or more arthrocentesis procedures out of the three tests on the joint on which they were trained. The minimum threshold value to be competent was calculated by a receiver operating characteristic curve and the Youden index. An assessment of theoretical knowledge and confidence level in joint arthrocente4.0 training arthrocentesis on a simulator is needed to achieve competency on a cadaver.The 5-hydroxytryptamine type-4 receptor agonist felcisetrag (TAK-954) is being investigated for improving gastrointestinal motility in postoperative gastrointestinal dysfunction. Polypharmacy often occurs in this setting, and as in vitro data indicate, felcisetrag is primarily metabolized by cytochrome P450 (CYP) 3A4, its CYP3A4-mediated drug-drug interaction potential requires consideration. This phase 1, fixed-sequence, open-label, crossover trial (ClinicalTrials.gov identifier NCT03173170) investigated the effect of itraconazole, a potent CYP3A4 inhibitor, on felcisetrag pharmacokinetics in healthy adults. Over 2 study periods (period 1, 6 days; period 2, 9 days), participants received a single felcisetrag 0.2-mg intravenous dose (day 1, period 1; and day 4, period 2), and once-daily oral itraconazole 200-mg doses (days 1-8, period 2). For felcisetrag alone, felcisetrag total systemic exposure was lower than with itraconazole coadministration. The geometric mean ratio for area under the plasma concentration-time curve from time 0 to infinity of felcisetrag plus itraconazole felcisetrag alone was 1.49 (90% confidence interval, 1.39-1.60). Peak exposure was similar between regimens (geometric mean ratio, 1.06; 90% confidence interval, 0.96-1.18), and both treatments were well tolerated. These data suggest limited CYP3A4-mediated drug-drug interaction inhibition for felcisetrag.Y6 and its derivatives have greatly improved the power conversion efficiency (PCE) of organic photovoltaics (OPVs). Further developing high-performance Y6 derivative acceptor materials through the relationship between the chemical structures and properties of these materials will help accelerate the development of OPV. Here, machine learning and quantum chemistry are used to understand the structure-property relationships and develop new OPV acceptor materials. By encoding the molecules with an improved one-hot code, the trained machine learning model shows good predictive performance, and 22 new acceptors with predicted PCE values greater than 17% within the virtual chemical space are screened out. Trends associated with the discovered high-performing molecules suggest that Y6 derivatives with medium-length side chains have higher performance. Further quantum chemistry calculations reveal that the end acceptor units mainly affect the frontier molecular orbital energy levels and the electrostatic potential on molecular surface, which in turn influence the performance of OPV devices. A series of promising Y6 derivative candidates is screened out and a rational design guide for developing high-performance OPV acceptors is provided. The approach in this work can be extended to other material systems for rapid materials discovery and can provide a framework for designing novel and promising OPV materials.Microplastics are an emergent yet critical issue for the environment because of high degradation resistance and bioaccumulation. Unfortunately, the current technologies to remove, recycle, or degrade microplastics are insufficient for complete elimination. In addition, the fragmentation and degradation of mismanaged plastic wastes in environment have recently been identified as a significant source of microplastics. Thus, the developments of effective microplastics removal methods, as well as, plastics recycling strategies are crucial to build a microplastics-free environment. Herein, this review comprehensively summarizes the current technologies for eliminating microplastics from the environment and highlights two key aspects to achieve this goal 1) Catalytic degradation of microplastics into environmentally friendly organics (carbon dioxide and water); 2) catalytic recycling and upcycling plastic wastes into monomers, fuels, and valorized chemicals. The mechanisms, catalysts, feasibility, and challenges of these methods are also discussed. Novel catalytic methods such as, photocatalysis, advanced oxidation process, and biotechnology are promising and eco-friendly candidates to transform microplastics and plastic wastes into environmentally benign and valuable products. In the future, more effort is encouraged to develop eco-friendly methods for the catalytic conversion of plastics into valuable products with high efficiency, high product selectivity, and low cost under mild conditions.Increasing antibiotic resistance becomes a serious threat to public health. Photothermal therapy (PTT) and antibacterial enzyme-based therapy are promising nonresistant strategies for efficiently killing drug-resistant bacteria. However, the poor thermostability of enzymes in PTT hinders their synergistic therapy. Herein, antibacterial glucose oxidase (GOx) is embedded in a Ag graphitic nanocapsule (Ag@G) arrayed silk film to fabricate a GOx-synergistic PTT system (named silk-GOx-Ag@G, SGA). The SGA system can stabilize GOx by a vitrification process through the restriction of hydrogen bond and rigid β-sheet, and keep the antibacterial activity in the hyperthermal PTT environment. Moreover, the arrayed Ag@G possesses excellent chemical stability due to the protection of graphitic shell, providing stable plasmonic effect for integrating PTT and surface enhanced Raman scattering (SERS) analysis even in the GOx-produced H2 O2 environment. With in situ SERS identification of bacterial intrinsic signals in the mouse wound model, such SGA realizes superior synergistic antibacterial effect on the infected Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus in vivo, while without causing significant biotoxicity. This system provides a therapeutic method with low resistance and in situ diagnosis capability for efficiently eliminating bacteria.Total joint arthroplasty (TJA) is an effective elective surgical procedure for knee and hip osteoarthritis (OA), yet racial disparities in the use of and outcomes from TJA have been recognized. Racial minority individuals are less willing to undergo TJA, demonstrate worse surgical and functional outcomes, and are more likely to undergo surgery at a low-procedure-volume center. In this systematic review, we summarize evidence to date on racial disparities in TJA and discuss potential factors that may underlie this gap in care for patients with OA.Tyrosinase-mediated melanin synthesis is an essential biological process that can protect skin from UV radiation and radical species. This work reports on in situ biosynthesis of artificial melanin in native skin using photoactivatable tyrosinase (PaTy). The I41Y mutant of Streptomyces avermitilis tyrosinase (SaTy) shows enzymatic activity comparable to that of wild-type SaTy. This Y41 is replaced with photocleavable o-nitrobenzyl tyrosine (ONBY) using the introduction of amber codon and ONBY-tRNA synthetase/tRNA pairs. The ONBY efficiently blocks the active site and tyrosinase activity is rapidly recovered by the photo-cleavage of ONBY. The activated PaTy successfully oxidizes L-tyrosine and tyramine-conjugated hyaluronic acid (HA_T) to synthesize melanin particles and hydrogel, respectively. To produce artificial melanin in living tissues, PaTy is encapsulated into lipid nanoparticles as an artificial melanosome. Using liposomes containing PaTy (PaTy_Lip), PaTy is transdermally delivered into ex vivo porcine skin and in vivo mouse skin tissues, thus achieving the in situ biosynthesis of artificial melanin for skin tissue protection under UV irradiation. The results of this study demonstrate that this biomimetic system can recapitulate the biosynthetic analogs of naturally occurring melanin. It should therefore be considered to be a promising strategy for producing protective biological molecules within living systems for tissue protection.NPC-21 (EV2038) is a fully human monoclonal antibody that targets the antigenic domain 1 of glycoprotein B on the human cytomegalovirus (hCMV) envelope. NPC-21 has been shown to have broadly neutralizing activity and to inhibit cell-to-cell transmission of hCMV in preclinical studies. It is currently in development for the prophylactic or preemptive treatment of hCMV in patients receiving a solid-organ transplant or hematopoietic stem cell transplant. A first-in-human phase 1 study was conducted to assess the pharmacokinetics, safety, and tolerability of NPC-21 in healthy adult men. Forty participants (Japanese, n = 32; White, n = 8) were randomly assigned to receive a single intravenous dose of NPC-21 1, 3, 10, or 20 mg/kg or placebo. selleck Six Japanese participants were included in each dose group and six White participants received a 10-mg/kg dose. The placebo group included 8 Japanese participants and 2 White participants. All 40 participants completed the study. Serum concentration, maximum serum concentration, area under the plasma concentration-time curve from time 0 to the last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity increased dose dependently; dose proportionality was linear.