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The ongoing global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been posing challenges to proper patients' management. Lungs are the first, and often the most affected organ by SARS-CoV-2; viral infection involves and damages both epithelial and vascular compartments, sometimes leading to severe and even fatal acute respiratory distress syndrome. Histopathological findings, mainly from postmortem examination of COVID-19 deceased patients, have been increasingly published in the last few months, helping to elucidate the sequence of events resulting in organ injury, and the complex multifactorial pathogenesis of this novel disease. A multidisciplinary approach to autopsy, including light microscopy examination along with the detection of viral proteins and/or RNA in tissue samples through ancillary techniques, provided crucial information on the mechanisms underlying the often-heterogeneous clinical picture of COVID-19.
The aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.
We searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. #link# The protocol is available at PROSPERO (CRD42020180915).
From 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria.equired to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events.
Due to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events.This article is the second in a series on asthma. The first article identified that the UK is experiencing an 'epidemic' of childhood asthma and one of the major culprits is air pollution. This article examines the main causes of air pollution and how they affect the lung health of children from before birth and onwards. It considers the contribution of indoor and outdoor air pollution, how these have changed over time and the unequal effect they may have on vulnerable populations. The nurse's role is discussed, not only in terms of clinical care, but also as adviser to families and schools on what actions to take to limit their exposure and reduce their own emissions of pollutants.The insertion of an indwelling urethral urinary catheter is an invasive procedure that is commonly undertaken in healthcare settings. However, there are click here and potential complications associated with these devices, so their use should be avoided where possible. It is important that nurses are equipped with the necessary knowledge and skills not only to assess if a patient requires a catheter, but also to minimise the risk of associated complications and to understand how these can be managed. This article discusses some of the common complications that can occur with the use of indwelling urinary catheters, including catheter-associated urinary tract infections; catheter blockages; encrustation; negative pressure; bladder spasm and trauma; and, in men, paraphimosis. It also explains the steps that nurses can take to reduce the risk of these complications and how to manage them effectively.The newest generation of drug delivery systems (DDSs) exploits ligands to mediate specific targeting of cells and/or tissues. However, studies investigating the link between ligand density and nanoparticle (NP) uptake are limited to a small number of ligand-receptor systems. C-type lectin-like molecule-1 (CLL1) is uniquely expressed on myeloid cells, which enables the development of receptors specifically targeting treat various diseases. This study aims to investigate how NPs with different CLL1 targeting peptide density impact cellular uptake. To this end, poly(styrene-alt-maleic anhydride)-b-poly(styrene) NPs are functionalized with cyclized CLL1 binding peptides (cCBP) ranging from 240 ± 12 to 31 000 ± 940 peptides per NP. Unexpectedly, the percentage of cells with internalized NPs is decreased for all cCBP-NP designs regardless of ligand density compared to unmodified NPs. link2 Internalization through CLL1 receptor-mediated processes is further investigated without confounding the effects of NP size and surface charge. Interestingly, high density cCBP-NPs (>7000 cCBP per NP) uptake is dominated by CLL1 receptor-mediated processes while low density cCBP-NPs (≈200 cCBP per NP) and untargeted NP occurred through non-specific clathrin and caveolin-mediated endocytosis. Altogether, these studies show that ligand density and uptake mechanism should be carefully investigated for specific ligand-receptor systems for the design of targeted DDSs to achieve effective drug delivery.The heterogeneous and anisotropic articular cartilage is generally studied as a layered structure of "zones" with unique composition and architecture, which is difficult to recapitulate using current approaches. A novel hybrid bioprinting strategy is presented here to generate zonally stratified cartilage. Scaffold-free tissue strands (TSs) are made of human adipose-derived stem cells (ADSCs) or predifferentiated ADSCs. Cartilage TSs with predifferentiated ADSCs exhibit improved mechanical properties and upregulated expression of cartilage-specific markers at both transcription and protein levels as compared to TSs with ADSCs being differentiated in the form of strands and TSs of nontransfected ADSCs. Using the novel hybrid approach integrating new aspiration-assisted and extrusion-based bioprinting techniques, the bioprinting of zonally stratified cartilage with vertically aligned TSs at the bottom zone and horizontally aligned TSs at the superficial zone is demonstrated, in which collagen fibers are aligned with designated orientation in each zone imitating the anatomical regions and matrix orientation of native articular cartilage. In addition, mechanical testing study reveals a compression modulus of ≈1.1 MPa, which is similar to that of human articular cartilage. The prominent findings highlight the potential of this novel bioprinting approach for building biologically, mechanically, and histologically relevant cartilage for tissue engineering purposes.
Platinum-based chemotherapy is currently the most frequently applied first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) without targetable mutations or high PD-L1 expression. Unfortunately, chemotherapy-induced toxicity is prevalent and may affect patients' quality of life to a considerable extent. Presumably, genetic variants of genes, coding for proteins involved in the processes of the development of toxicity, may be of interest as predictors of benefits and harms of platinum-based chemotherapy. The primary objective of the study is to investigate the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy. The main secondary objectives are to study the association between genetic variants and treatment response and to study the association between skeletal muscle mass (SMM) as well as patient-reported health-related quality of life (HRQOL) and treatment response and toxicity.
ce of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy.T lymphocytes are the central coordinator and executor of many immune functions. The activation and function of T lymphocytes are mediated through the engagement of cell surface receptors and regulated by a myriad of intracellular signaling network. Bioengineering tools, including imaging modalities and fluorescent probes, have been developed and employed to elucidate the cellular events throughout the functional lifespan of T cells. A better understanding of these events can broaden our knowledge in the immune systems biology, as well as accelerate the development of effective diagnostics and immunotherapies. Here we review the commonly used and recently developed techniques and probes for monitoring T lymphocyte intracellular events, following the order of intracellular events in T cells from activation, signaling, metabolism to apoptosis. The techniques introduced here can be broadly applied to other immune cells and cell systems. link3 This article is categorized under Immune System Diseases > Molecular and Cellular Physiology Immune System Diseases > Biomedical Engineering Infectious Diseases > Biomedical Engineering.Drug-drug interactions (DDIs) occur when the pharmacological activity of one drug is altered by a second drug. As multimorbidity and polypharmacotherapy are becoming more common due to the increasing age of the population, the risk of DDIs is massively increasing. Therefore, in vitro testing methods are needed to capture such multiorgan events. Here, a scalable, gravity-driven microfluidic system featuring 3D microtissues (MTs) that represent different organs for the prediction of drug-drug interactions is used. Human liver microtissues (hLiMTs) are combined with tumor microtissues (TuMTs) and treated with drug combinations that are known to cause DDIs in vivo. The testing system is able to capture and quantify DDIs upon co-administration of the anticancer prodrugs cyclophosphamide or ifosfamide with the antiretroviral drug ritonavir. Dosage of ritonavir inhibits hepatic metabolization of the two prodrugs to different extents and decreases their efficacy in acting on TuMTs. The flexible MT compartment design of the system, the use of polystyrene as chip material, and the assembly of several chips in stackable plates offer the potential to significantly advance preclinical substance testing. The possibility of testing a broad variety of drug combinations to identify possible DDIs will improve the drug development process and increase patient safety.Tissue engineered vascular grafts (TEVGs) are a promising technology, but are hindered by occlusion. Seeding with bone-marrow derived mononuclear cells (BM-MNCs) mitigates occlusion, yet the precise mechanism remains unclear. Seeded cells disappear quickly and potentially mediate an anti-inflammatory effect through paracrine signaling. Here, a series of reciprocal genetic TEVG implantations plus recombinant protein treatment is reported to investigate what role interleukin-10, an anti-inflammatory cytokine, plays from both host and seeded cells. TEVGs seeded with BM-MNCs from wild-type and IL-10 KO mice, plus unseeded grafts, are implanted into wild-type and IL-10 KO mice. Wild-type mice with unseeded grafts also receive recombinant IL-10. Serial ultrasound evaluates occlusion and TEVGs are harvested at 14 d for immunohistochemical analysis. TEVGs in IL-10 KO mice have significantly higher occlusion incidence compared to wild-type mice attributed to acute ( less then 3 d) thrombosis. Cell seeding rescues TEVGs in IL-10 KO mice comparable to wild-type patency.
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