Superparamagnetic iron oxide polyacrylic acid coated {\gamma}-Fe2O3 nanoparticles does not affect kidney function but causes acute effect on the cardiovascular function in healthy mice

This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated {\gamma}-Fe2O3 NPs (10 mg kg-1) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid-base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46 and 7.41 in mice 0.5 h after injections of saline or NP, and did not change over the next 12h. In addition, the injections of NP did not affect arterial PCO2 or [HCO3-] either. Twenty-four and 96h after NP injections, the GFR averaged 11.0 and 13.0 ml min-1 g-1, respectively, values which were statistically comparable with controls (14.0 and 14.0 ml min-1 g-1). Mean arterial blood pressure (MAP) decreased 12-24h after NP injections (111 vs 123 min-1) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterise endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure.Comment: 21 pages, 12 figures, published in Toxicology and Applied Pharmacology 201

Living With Ovarian Cancer: Transitions Lost in Translation

Background: Living with ovarian cancer involves uncertainty, fear of recurrence, and premature death while preparing for a life after treatment. The women depend on health care professionals while moving from being healthy to experiencing ovarian cancer. Objective: To explore experiences of women living with ovarian cancer and their interactions with health care professionals. Methods: Five focus group interviews were conducted with the same 4 women, between 2018 and 2020. The interviews were analyzed using systematic text condensation. Results: Living with ovarian cancer involved a set of transitions from health to illness and disease. These transitions were difficult for the women to articulate to health care professionals, friends and family, and to themselves. All participants expressed the experiencing of existential and emotional chaos and paradoxes. As their illness developed, it impacted their ability to articulate changes to their body and sense of self and to their own identity negatively. Consequently, the women felt that their ability to communicate their needs to others, including to health care professionals, deteriorated as the disease progressed. Conclusions: Women living with ovarian cancer experience transitions lost in translation within themselves and in communication with persons in their personal, familial, and medical realms. Implications for Practice: A better understanding of their existential suffering and how it is easily lost in translation may refine care and support for these women throughout their illness and disease trajectory.publishedVersio

The association between preschool behavioural problems and internalizing difficulties at age 10-12 years

The aim was to study the association between preschool behavioural problems and emotional symptoms in 10- to 12-year-old children. The study was based on the Aarhus Birth cohort, Denmark, and included 1,336 children. Based on the parent-administered preschool behaviour questionnaire (PBQ), we identified three not mutually exclusive preschool behavioural categories: anxious–fearful (n = 146), hyperactive–distractible (n = 98), and hostile–aggressive (n = 170). Children without any known symptoms were considered well adjusted (n = 1,000). Borderline emotional (n = 105) and emotional difficulties (n = 136) were measured at age 10–12 years with the parent-administered strength and difficulties questionnaire (SDQ). Multinomial logistic regression analyses were used to adjust for potential confounding factors. We found that anxious–fearful behaviour and hostile–aggressive preschool behaviour were associated with twice the risk of school-age emotional difficulties. Comorbidity or confounding failed to explain these results. Hyperactive–distractible preschool behaviour was not associated with school-age emotional difficulties. Preschool anxious–fearful behaviour was associated with school-age emotional difficulties, suggesting internalizing symptom stability in some children from early childhood. Preschool hostile–aggressive behaviour was also associated with school-age emotional difficulties, which suggests transformation of one behavioural dimension into another through childhood, and the need to focus on both early internalizing difficulties and hostile–aggressive behaviour as risk factors for later internalizing difficulties

Role of ammonia in NAFLD: An unusual suspect

Mechanistically, the symptomatology and disease progression of non-alcoholic fatty liver disease (NAFLD) remain poorly understood, which makes therapeutic progress difficult. In this review, we focus on the potential importance of decreased urea cycle activity as a pathogenic mechanism. Urea synthesis is an exclusive hepatic function and is the body’s only on-demand and definitive pathway to remove toxic ammonia. The compromised urea cycle activity in NAFLD is likely caused by epigenetic damage to urea cycle enzyme genes and increased hepatocyte senescence. When the urea cycle is dysfunctional, ammonia accumulates in liver tissue and blood, as has been demonstrated in both animal models and patients with NAFLD. The problem may be augmented by parallel changes in the glutamine/glutamate system. In the liver, the accumulation of ammonia leads to inflammation, stellate cell activation and fibrogenesis, which is partially reversible. This may be an important mechanism for the transition of bland steatosis to steatohepatitis and further to cirrhosis and hepatocellular carcinoma. Systemic hyperammonaemia has widespread negative effects on other organs. Best known are the cerebral consequences that manifest as cognitive disturbances, which are prevalent in patients with NAFLD. Furthermore, high ammonia levels induce a negative muscle protein balance leading to sarcopenia, compromised immune function and increased risk of liver cancer. There is currently no rational way to reverse reduced urea cycle activity but there are promising animal and human reports of ammonia-lowering strategies correcting several of the mentioned untoward aspects of NAFLD. In conclusion, the ability of ammonia-lowering strategies to control the symptoms and prevent the progression of NAFLD should be explored in clinical trials