Elevated markers of gut leakage and inflammasome activation in COVID-19 patients with cardiac involvement.

BACKGROUND: A high proportion of COVID-19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID-19 patients. METHODS: Plasma levels of a gut leakage marker (LPS-binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL-1ß, IL-18 and their regulatory proteins) were measured at three time points (day 1, 3-5 and 7-10) in 39 hospitalized COVID-19 patients and related to cardiac involvement. RESULTS: Compared to controls, COVID-19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT-pro-BNP levels, whereas IL-18, IL-18BP and IL-1Ra were associated with higher troponin levels. CONCLUSION: Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut-heart axis in COVID-19.

Decisions to withhold or withdraw life-sustaining treatment in a Norwegian intensive care unit.

BACKGROUND: To withhold and withdraw treatment are important and difficult decisions made in the intensive care unit (ICU). The aim of this study was to investigate the incidence of withholding or withdrawing treatment, characteristics of the patients, and how these decision processes were handled and documented in a general ICU from 2007 to 2009 in a university hospital in Norway. METHODS: Patient characteristics and outcomes of treatment were prospectively registered. We retrospectively reviewed the medical records for information on limitations in treatment. RESULTS: In total, 1287 patients were admitted to the ICU. The ICU mortality was 208 (16%), and the hospital mortality was 341 (26%). In total, 301 patients (23%) had treatment withheld or withdrawn. Medical and unscheduled surgical patients with limitations in treatment had higher Simplified Acute Physiology Score II (P < 0.001) and were older (P < 0.001) than those without limitations in treatment. The most common main reason for withdrawing treatment was poor prognosis. According to the medical records, the patient was involved in the decision-making regarding withdrawal of treatment in only 2% of the cases, and the patient's relatives were involved in the decision-making in 77% of the cases. In 12% of the cases, type of treatment withdrawn was not documented. CONCLUSION: Withholding or withdrawing treatment in the ICU was common. Medical and unscheduled surgical patients with limitations in treatment were older and more severely ill than patients without limitations. There is a potential for better documentation of the processes regarding withholding or withdrawing life-sustaining intensive care treatment.

Polyelectrolyte multilayer capsules with quantum dots for biomedical applications.

The aim of this work was to encapsulate the CdTe quantum dots within the nanocapsules that were prepared by the layer-by-layer adsorption of polyelectrolytes. Two different polyelectrolyte pairs were used as components of the shell: synthetic polycation poly(allyamine hydrochloride) (PAH), together with anionic poly(sodium styrene sulfonate) (PSS), and biocompatible cationic poly-L-lysine hydrobromide in a pair with biocompatible anionic poly-D-glutamic acid sodium salt (PGA). The saturation method was used for formation of consecutive layers on the initial CdTe-polyelectrolyte complex. A growth of the polyelectrolyte shell was followed with the electrophoretic mobility and light scattering measurements, in order to determine the zeta potential and the size of capsules, respectively. The fluorescent spectra of the quantum dots, which are embedded within the capsules, were characterized with spectrofluorimeter. Later on, they were deposited on a negatively charged mica surface and studied by the means of atomic force microscopy (AFM). In order to estimate the cytotoxicity of capsules, their influence on the B-lymphoblastoid cell line proliferation and on unspecific binding to the P-blood mononuclear cells was examined using the flow cytometry.

Formation of biocompatible nanocapsules with emulsion core and pegylated shell by polyelectrolyte multilayer adsorption.

The aim of this work was to develop a novel method of preparation of loaded nanosize capsules based on liquid core encapsulation by biocompatible polyelectrolyte (PE) multilayer adsorption, with or without pegylated outermost layer. Using AOT (docusate sodium salt) as emulsifier, we obtained cores, stabilized by an AOT/PLL (poly-L-lysine hydrobromide) surface complex. These positively charged cores were encapsulated by layer-by-layer adsorption of polyelectrolytes, biocompatible polyanion PGA (poly-L-glutamic acid sodium salt), and biocompatible polycation PLL. We used the saturation method for formation of consecutive layers, and we determined the optimal conditions concerning concentration of surfactant and polyelectrolytes to form stable shells. The average size of the obtained capsules was 60 nm. Pegylated external layer were prepared using PGA-g-PEG (PGA grafted by PEG poly(ethylene glycol)). The capsules were stable for at least a period of 3 months. These nanocapsules were biocompatible when tested for cytotoxicity in a cellular coculture assay and demonstrated no or very low nonspecific binding to peripheral blood mononuclear cells when tested by flow cytometry. In order to study drug effects on leukemia cells, beta-carotene and vitamin A have been encapsulated as model drugs.

Expectations and realities of student nurses' experiences of negative behaviour and bullying in clinical placement and the influences of socialization processes.

This paper explores nursing students' experiences and perceptions of negative behaviour and bullying in clinical placement measured against expectations at the start of their education. It explores their understanding and how they make sense of their circumstances and their experiences of negative behaviour, emphasizing socialization processes and factors which may prevent or reproduce negative behaviour and bullying. To this end, a focus group study was conducted, and this revealed that many students felt exploited, ignored or were made to feel unwelcome, although few reported personal experience of bullying. These frequent but less severe negative experiences appear to play a key role in institutionalizing an unwelcoming culture within which bullying could easily be triggered or take hold. Students' coping mechanisms may also contribute to reproducing such negative behaviour. The paper concludes that while the vulnerable position of student nurses might offer some protection against outright bullying, it is unable to shield them from unfriendly and negative behaviour, with implications for their learning and professional socialization. If student nurses respond to their experiences by suppressing their feelings and developing a hard front, such responses may themselves contribute to a reproduction of such behaviour with implications for personal wellbeing and retention rates.

Occupational safety and health: a method to test the collection of 'grey data' by line managers.

This paper describes and discusses a method for collecting data relating to the potential for illness or injury to occur in an organization. The reason for using the term 'grey' is explained and the underpinning philosophy of fuzzy thinking is also discussed. The method used was an audit which attempted to measure the degree to which certain types of failure were present in one organization. The audit used a term approach in design and execution and was found to be a useful and useable tool for collecting information relating potential causes of injury or illness.

The perceptions of line and senior managers in relation to occupational health issues.

Perceptions of line and senior managers in relation to their role in managing workplace injury and illness were investigated with a large UK manufacturing company. The significance of this research to occupational health practitioners lies in the fact that increased understanding of the perceptions of senior and line managers is fundamental to the success of occupational safety and health programmes. Documentary analysis and semi-structured interviews were used to assess perceptions. The findings showed that the managers had a much sounder understanding of their role in injury prevention than that related to illness prevention. The way in which information relating to injury and illness data is presented to managers to aid decision making was found likely to be a fruitful area for further research.