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We then show that despite similar accumulation in brains harboring TNBC tumors, Fn14-targeted DARTs exhibit significant and specific association with Fn14-positive TNBC cells compared to nontargeted NPs or Abraxane. Together, these results indicate that Fn14 expression primarily by tumor cells in TNBC BMs enables selective DART NP delivery to these cells, likely driving the significantly improved therapeutic efficacy observed in our prior work.

To evaluate the activity of fosfomycin against a group of MRSA strains, including isolates with reduced susceptibility or resistance to vancomycin, daptomycin, linezolid and ceftaroline and to determine the effect of combining various combinations of antimicrobial agents used in the therapy of serious Gram-positive infections.

Broth microdilution testing was used to determine the MICs of fosfomycin, vancomycin, daptomycin, linezolid, ceftaroline and cefazolin. Isolates were selected for further evaluations to determine in vitro synergy between fosfomycin and select antimicrobial agents using chequerboard broth microdilution testing. Fosfomycin was tested in combination with vancomycin, linezolid, daptomycin, ceftaroline and cefazolin.

Fosfomycin maintained activity against 100% of strains of vancomycin-resistant Staphylococcus aureus (VRSA) and linezolid-resistant S. aureus (LRSA), 86% of VISA and 95% of daptomycin-resistant S. aureus (DRSA) strains. The combination of fosfomycin with ceftaroline consisen combined with linezolid or daptomycin, fosfomycin demonstrated synergy for all or most strains tested. Thus, these combinations may have potential clinical utility when treating patients with serious infections caused by MRSA.Difficult healing of diabetic foot ulcers is associated with overexpression of matrix metalloproteinase 9 (MMP-9) in the local wound. Therefore, strategies aimed at downregulation of MMP-9 levels in ulcer sites may promote tissue regeneration and accelerate healing of diabetic foot ulcers (DFU). To fulfill this aim, we exploited dextran conjugated with poly(amidoamine) (Dextran-PAMAM) as a gene carrier to deliver MMP-9 targeted siRNA (siMMP-9). The prepared complexes could be efficiently endocytosed with low cytotoxicity to HaCat cells. Dextran-PAMAM could efficiently deliver siMMP-9 and significantly inhibit MMP-9 expression in vitro. Diabetic rats wound models showed that topical application of the Dextran-PAMAM/siMMP-9 complex effectively knocked down MMP-9 expression in skin wound tissue, thus accelerating wound healing. Taken together, this study demonstrates that the Dextran-PAMAM/siMMP-9 complex possesses high potential for wound healing and could serve as a promising regenerative platform for improving DFU healing.

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disease characterized by osteonecrosis of the femoral head. Because severe deformity of the femoral head can cause secondary osteoarthritis in adulthood, progressive collapse should be prevented in children with a necrotic epiphysis. The prognosis of patients with LCPD generally worsens as the age at disease onset increases, and the appropriate treatment for late-onset LCPD remains unclear. Based on the limited effect of nonoperative treatment using a nonweightbearing brace, flexion varus osteotomy (FVO) was introduced in 2010 as an initial treatment for late-onset LCPD in place of brace treatment, which we used in our institution before that time.

We asked, (1) Which treatment, FVO or a nonweightbearing brace, is associated with a lower likelihood of progressive femoral head collapse in children whose diagnosis of LCPD was made at the age of ≥ 8 years and who were followed for a minimum of 3 years after their intervention? (2) What proportion of patienss I or II) compared with brace treatment for patients with late-onset LCPD, although surgical interventions after the first and second implant removal procedures may be indicated. Surgeons can consider FVO if they encounter patients with late-onset LCPD, which is a challenging condition. A larger study with long-term follow-up is needed to confirm the efficacy of FVO.

Level III, therapeutic study.

Level III, therapeutic study.

Hydroxychloroquine and ivermectin received widespread attention after initial studies suggested that they were effective against COVID-19. However, several of these studies were later discredited.

We explored the impact of scientific articles, public announcements and social media posts on hydroxychloroquine and ivermectin purchases in the USA and Canada during the COVID-19 pandemic.

We conducted a retrospective, population-based time series analysis of retail hydroxychloroquine and ivermectin purchases in the USA and Canada from February 2016 through to December 2021, using IQVIA's Multinational Integrated Data Analysis database. We fitted the purchasing rates with interventional autoregressive integrated moving average models. We used Google Trends to identify the most influential interventions to include in the models.

There were significant pulse increases in hydroxychloroquine purchases in March 2020 in both the USA (P < 0.0001) and Canada (P < 0.0001). For ivermectin, there were no significant changes in April 2020 in either the USA (P = 0.41) or Canada (P = 0.16); however, significant pulse increases occurred from December 2020 to January 2021 in both the USA (P = 0.0006) and Canada (P < 0.0001), as well as significant ramp increases from April to August 2021 in both the USA (P < 0.0001) and Canada (P = 0.02). The increases in ivermectin purchases were larger in the USA than in Canada.

Increases in hydroxychloroquine and ivermectin purchasing rates aligned with controversial scientific articles and social media posts. This highlights the importance of scientific integrity and disseminating accurate epidemiologic information during pandemics.

Increases in hydroxychloroquine and ivermectin purchasing rates aligned with controversial scientific articles and social media posts. This highlights the importance of scientific integrity and disseminating accurate epidemiologic information during pandemics.Individuals with genetic gain-of-function variation in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene are at an increased risk of cardiovascular disease, including ischemic stroke. While PCSK9 inhibitors (PCSK9i) are effective in reducing cardiovascular disease risk and ischemic stroke risk, novel genomic technologies including the use of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 complex-mediated delivery and adenine base editing (ABE) enable promising new therapeutic and preventative approaches. In this paper we discuss ongoing work into PCSK9 base editing and highlight future directions relevant to cardiovascular disease and ischemic stroke.

Subcutaneous (SC) administration of antibiotics represents an attractive alternative to the intravenous (IV) route.

We performed a systematic electronic search of PubMed and the Cochrane Library for all articles published prior to April 2022, using the key terms and MeSH terms 'subcutaneous', 'antibiotic' and the international non-proprietary name of antibiotics.

A total of 30 studies were selected including data on the efficacy and tolerability of antibiotics, and seven studies that were conducted in healthy subjects, for relevant information regarding the safety and tolerability of antibiotics. Comparative studies have shown that efficacy is similar for the SC and IV routes for ceftriaxone, teicoplanin and ertapenem. The SC use of other antibiotics such as ampicillin, ceftazidime, cefepime, piperacillin/tazobactam, metronidazole and fosfomycin has also been described. These results have largely been corroborated by pharmacokinetic/pharmacodynamic analyses, especially for time-dependent antibiotics. Co antibiotics could be administered subcutaneously, but further studies are needed to validate their use in clinical practice. Further research is needed to safely generalize and optimize this route of administration whenever possible. This would reduce the risk of catheter-related infections and their complications, together with the length of hospital stay.Highly active and stable oxygen evolution reaction (OER) electrocatalysts for water electrolysis are currently in high demand. Herein, a rationally designed three-dimensional (3D) CoFe selenide porous array (Fe-CoSe PA) is synthesized through ion exchange from zeolitic imidazolate framework-L (ZIF-L) nanoarray, followed by a facile selenization under hydrothermal conditions for OER electrocatalysis. During the OER process, the surface of Fe-CoSe PA is rapidly oxidized to CoFe oxides/hydroxides, which prevents the inner layer from being oxidized. Benefiting from the high porosity, abundant active sites, and the high conductivity of inner Fe-CoSe, Fe-CoSe PA exhibits excellent OER performance, with an overpotential of 285 mV at a current density of 10 mA cm-2, and a small Tafel slope of 68 mV dec-1, as well as high stability under 50 h of continuous testing. The present work could provide a facile route for fabricating 3D porous selenides for highly efficient OER catalysis.

Resistance exercise is a well-established intervention to counteract musculoskeletal and metabolic toxicities from prostate cancer treatment. In this study, we reported resistance exercise attendance and compliance, and examine if these variables can influence changes in outcomes of interest in men with localised or locally advanced prostate cancer.

A total of 83 prostate cancer patients (age 68.2 ± 7.0 years, body mass index 27.7 ± 3.8 kg.m -2 ) who had undergone 6 months of resistance-based exercise and had data available on exercise training from logbook records were examined. Attendance outcomes such as missed sessions, interruptions and permanent discontinuation, and metrics such as dosage completed (sessions x number of exercises x sets x repetitions x external load), compliance, tolerance, reductions and escalations were assessed. Bucladesine Outcomes assessed were body composition, physical function and muscle strength.

Median resistance exercise attendance was 80.6%, with a median resistance exercise complreater improvements in regional fat and lean mass, while physical function and muscle strength improvements were achieved with lower compliance. Additionally, patients experienced a high number of dose escalations during the intervention. These findings are important to improve the reproducibility/precision of exercise medicine prescription.Oxidative rancidity is a major issue limiting the utilization of flaxseed oil (FSO). Peptides possess an antioxidant effect; however, the flax cyclic peptide, a unique ingredient in FSO, has an obscure influence on the oxidation of FSO. Therefore, this study is aimed to investigate the effects of [1-9-NαC]-linusorb B3 (CLA) on the accelerated oxidation of FSO and the underlying mechanism. We found that CLA increased the antioxidant stability of refined flaxseed oil (RFO), indicated by the improved parameters involved in the oxidation after the addition of CLA. After accelerated oxidation, the acid value (AV) of the RFO was increased by 24.14 times, whereas that of the RFO with CLA (CLA-RFO) increased only by 7.21 times. Similarly, the peroxide value (POV) and P-anisidine value (P-AV) of CLA-RFO were significantly decreased. Besides, CLA influenced metal ions-induced oxidation. In the Cu2+ group, the addition of CLA reduced the AV by 18% and the POV by 20%. The results of the molecular docking analysis and fluorescence quenching showed that the metal ions and propionaldehyde interacted with the cavity of CLA, and propionaldehyde had the most stable binding configuration with CLA, indicating that CLA may slow down the oxidation of FSO by chelating the metal ions and the intermediate oxidative products.