PVA-Based Hydrogels Loaded with Diclofenac for Cartilage Replacement

Polyvinyl alcohol (PVA) hydrogels have been widely studied for cartilage replacement due to their biocompatibility, chemical stability, and ability to be modified such that they approximate natural tissue behavior. Additionally, they may also be used with advantages as local drug delivery systems. However, their properties are not yet the most adequate for such applications. This work aimed to develop new PVA-based hydrogels for this purpose, displaying improved tribomechani- cal properties with the ability to control the release of diclofenac (DFN). Four types of PVA-based hydrogels were prepared via freeze-thawing: PVA, PVA/PAA (by polyacrylic acid (PAA) addition), PVA/PAA+PEG (by polyethylene glycol (PEG) immersion), and PVA/PAA+PEG+A (by annealing). Their morphology, water uptake, mechanical and rheological properties, wettability, friction coef- ficient, and drug release behavior were accessed. The irritability of the best-performing material was investigated. The results showed that the PAA addition increased the swelling and drug release amount. PEG immersion led to a more compact structure and significantly improved the material’s tribomechanical performance. The annealing treatment led to the material with the most suitable properties: besides presenting a low friction coefficient, it further enhanced the mechanical properties and ensured a controlled DFN release for at least 3 days. Moreover, it did not reveal irritability potential for biological tissues.info:eu-repo/semantics/publishedVersio

PVA-Based Hydrogels Loaded with Diclofenac for Cartilage Replacement

Polyvinyl alcohol (PVA) hydrogels have been widely studied for cartilage replacement due to their biocompatibility, chemical stability, and ability to be modified such that they approximate natural tissue behavior. Additionally, they may also be used with advantages as local drug delivery systems. However, their properties are not yet the most adequate for such applications. This work aimed to develop new PVA-based hydrogels for this purpose, displaying improved tribomechanical properties with the ability to control the release of diclofenac (DFN). Four types of PVA-based hydrogels were prepared via freeze-thawing: PVA, PVA/PAA (by polyacrylic acid (PAA) addition), PVA/PAA+PEG (by polyethylene glycol (PEG) immersion), and PVA/PAA+PEG+A (by annealing). Their morphology, water uptake, mechanical and rheological properties, wettability, friction coefficient, and drug release behavior were accessed. The irritability of the best-performing material was investigated. The results showed that the PAA addition increased the swelling and drug release amount. PEG immersion led to a more compact structure and significantly improved the material’s tribomechanical performance. The annealing treatment led to the material with the most suitable properties: besides presenting a low friction coefficient, it further enhanced the mechanical properties and ensured a controlled DFN release for at least 3 days. Moreover, it did not reveal irritability potential for biological tissues

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute