Thrombotic occlusions of blood vessels are responsible for life-threatening cardiovascular disorders such as myocardial infarction, ischemic stroke, and venous thromboembolism. Current thrombolytic therapy, the injection of Plasminogen Activators (PA), is yet limited by a narrow therapeutic window, rapid drug elimination, and risks of hemorrhagic complications. Nanomedicine-based vectorization of PA protects the drug from the enzymatic degradation, improves the therapeutic outcomes, and diminishes adverse effects in preclinical models. Herein, we review the pathophysiology of arterial and venous thrombosis and summarize clinically approved PA for the treatment of acute thrombotic diseases. We examine current challenges and perspectives in the recent key research on various (lipid, polymeric, inorganic, biological) targeted nanocarriers intended for the site-specific delivery of PA. Microbubbles and ultrasound-assisted sonothrombolysis that demonstrate thrombolysis enhancement in clinical trials are further discussed.  https://www.selleckchem.com/products/kpt-8602.html  Moreover, this review features strategies for the rational design of nanocarriers for targeted thrombolysis and effective PA encapsulation in view of interactions between nanomaterials and biological systems. Overall, nanomedicine represents a valued approach for the precise treatment of acute thrombotic pathologies.Chronic kidney disease of unknown etiology (CKDu) is an emerging global concern affecting several agricultural communities in the Americas and South Asia. Environmental contaminants such as heavy metals (e.g., Cd, As, Pb, and V) and organic pesticides (e.g., glyphosate) in the drinking water have been hypothesized to play a role in childhood onset and progression of this disease. However, a comprehensive analysis of chemical contaminants in the drinking water and effects of these compounds and their mixtures on kidney development and function remains unknown. Here, we conducted targeted and non-targeted chemical analyses of sediment and drinking water in CKDu affected regions in Sri Lanka, one of the most affected countries. Using zebrafish Danio rerio, a toxicology and kidney disease model, we then examined kidney developmental effects of exposure to (i) environmentally derived samples from CKDu endemic and non-endemic regions and (ii) Cd, As, V, Pb, and glyphosate as individual compounds and in mixtures. We found that drinking water is contaminated with various organic chemicals including nephrotoxic compounds as well as heavy metals, but at levels considered safe for drinking. Histological studies and gene expression analyses examining markers of kidney development (pax2a) and kidney injury (kim1) showed novel metal and glyphosate-metal mixture specific effects on kidney development. Mitochondrial dysfunction is directly linked to kidney failure, and examination of mixture specific mitochondrial toxicity showed altered mitochondrial function following treatment with environmental samples from endemic regions. Collectively, we show that metals in drinking water, even at safe levels, can impede kidney development at an early age, potentiating increased susceptibility to other agrochemicals such as glyphosate. Drinking water contaminant effects on mitochondria can further contribute to progression of kidney dysfunction and our mitochondrial assay may help identify regions at risk of CKDu.Exposure of humans to organophosphate flame retardants (OPFRs) and the consequent health risk have increased owing to the latter's widespread application. Although triphenyl phosphate (TPP), an OPFR, is a potential chemical determinant of liver function damage, its effects on kidney function in mice under high fructose/fat (HFF) diet are still unclear. In this study, C57BL/6J mice were fed HFF to generate an obesity model and mice were exposed to low dose (0.01 mg/kg/day; TPP-L) and high dose (1 mg/kg/day; TPP-H) of TPP for 12 weeks. Results showed that TPP-L and TPP-H combined with HFF, as well as TPP-H alone, caused kidney structural damage and gut microbiota disorders in mice. Inflammatory response induced by nuclear factor kappa B (NF-κB p65)/nod-like receptor protein 3 (NLRP3) and caspase-3 promoted kidney structure damage, as well as accumulation of triglyceride and total cholesterol and the protein residues in urine. Although TPP-L did not cause obvious structural damage in the kidneys, 0.01 mg/kg TPP induced significant inflammation and gut microbiota disorders. These findings provide new insights regarding health risk assessment after chronic exposure to TPP and HFF alone, as well as a combination of TPP with HFF in mice.
  Attempts to improve child protection outcomes by implementing social work practice models embedded in a particular theory and practice approach, have increased internationally over the past decade.
 
  To assess the evidence of the effectiveness of child protection practice models in improving outcomes for children and families.
 
  Children < 18 years and their families involved in child protection services.
 
  A systematic review was conducted to synthesize evidence regarding the effectiveness of child protection practice models. Systematic searches across 10 electronic databases and grey literature were conducted to identify quasi-experimental studies minimally. Included studies were critically appraised and the findings summarized narratively.
 
  Five papers, representing six studies, focusing on three practice models (Solution-Based Casework; Signs of Safety; and Reclaiming Social Work) met the inclusion criteria. All studies applied a quasi-experimental design. Overall, the quality of the evidence was raare, and these challenges and future directions for research, are discussed. PROSPERO registration number CRD42018111918.During drier periods estuarine salinization can stimulate the colonization of marine organisms and further bioinvasion, therefore, may cause future ecological change. In this sense, we applied the Rapid Assessment Surveys (RAS) on natural and artificial hard substrates during the most intense drought period (between 2014 and 2016) since 1950, in a tropical estuary in Eastern Brazil. Through the estuary salinization the ascidian Didemnum psammatodes overgrow the dominant native taxa; this dominance taxa shift provided suitable habitat favorable for invasion of Ophiothela mirabilis across the estuary. Even the invasion starts on artificial substrates, the higher resilience of natural substrates were not enough to enable the establishment of invasive species. This baseline is the first evidence of bioinvasion influenced by climate change drought periods in tropical estuaries in South America, which is a great advance for the development of management strategies to mitigate this and future climate change scenarios.