Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Cassava as drought insurance: Food security implications of cassava trials in Central Zambia

Wide, weather-induced fluctuations in maize production lead to recurrent food shortages in Zambia's maize consuming regions, while the cassava-growing regions of the north enjoy stable food production, even in drought years. Noting this striking correlation between drought vulnerability and the prevalence of maize as a staple food, a growing array of agencies in Zambia has begun introducing highly productive new cassava varieties, developed in the north, to more central and southerly regions in an effort to provide low-cost food security during drought years. Yet agroecological conditions in these drought-prone regions differ significantly from the northern research stations where Zambian scientists developed the new cassava varieties. So it is not clear that the varieties or management practices that work well in the north will prove optimal in other regions. In order to assist farmers and agencies interested in expanding cassava as a food security crop in central Zambia, we have conducted cassava trials in central Zambia over the past three years. Concurrently, we have engaged in regular onfarm discussions with early adopting farmers. Results from these investigations suggest that, with some modification of management practices recommended in the north, many of the new cassava clones offer a feasible means of mitigating lean season hunger and providing low-cost, in-kind drought insurance for rural households in central Zambia

Cassava as drought insurance: Food security implications of cassava trials in Central Zambia

Wide, weather-induced fluctuations in maize production lead to recurrent food shortages in Zambia's maize consuming regions, while the cassava-growing regions of the north enjoy stable food production, even in drought years. Noting this striking correlation between drought vulnerability and the prevalence of maize as a staple food, a growing array of agencies in Zambia has begun introducing highly productive new cassava varieties, developed in the north, to more central and southerly regions in an effort to provide low-cost food security during drought years. Yet agroecological conditions in these drought-prone regions differ significantly from the northern research stations where Zambian scientists developed the new cassava varieties. So it is not clear that the varieties or management practices that work well in the north will prove optimal in other regions. In order to assist farmers and agencies interested in expanding cassava as a food security crop in central Zambia, we have conducted cassava trials in central Zambia over the past three years. Concurrently, we have engaged in regular onfarm discussions with early adopting farmers. Results from these investigations suggest that, with some modification of management practices recommended in the north, many of the new cassava clones offer a feasible means of mitigating lean season hunger and providing low-cost, in-kind drought insurance for rural households in central Zambia.Food Security and Poverty,

Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies

Background oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors