Neurotoxin-derived optical probes for biological and medical imaging

The superb specificity and potency of biological toxins targeting ion channels and receptors are of major interest for delivering therapeutics to distinct cell types and subcellular compartments. Fused with reporter proteins or labelled with fluorophores and nanocomposites, animal toxins and their detoxified variants also offer expanding opportunities for visualization of a range of molecular processes and functions in preclinical models, as well as clinical studies. This article presents state-of-the-art optical probes derived from neurotoxins targeting ion channels, with discussions of their applications in basic and translational biomedical research. It describes the details of the design and production of probes and reviews their applications with advantages and limitations, with prospects for future improvements. Given the advances in imaging tools and expanding research areas benefiting from the use of optical probes, the resources described here should assist the discovery process and facilitate high-precision research and therapeutic interventions

The Direct Medical Cost of Regular Monitoring of Patients with HBeAg-Negative Chronic Hepatitis B Virus Infection

Objectives: Patients with hepatitis B e antigen-negative chronic infection (inactive carriers) account for most of the people living with hepatitis B virus (HBV). This study investigated the direct medical cost of monitoring patients within this group.Materials and Methods: A total of 293 outpatients receiving regular monitoring in a large university hospital were included in the study. Direct medical costs included laboratory tests, imaging, liver biopsies and co-payments. Linear mixed effect models were applied to investigate the effect of follow-up time on the annual cost of monitoring. We made quarterly, semi-annual and annual monitoring cost trajectories in accordance with international guideline recommendations.Results: The average annual direct medical cost per patient was 160 USD and the average laboratory visit cost per patient was 68.5 USD. HBV DNA testing contributed to a majority percentage of the total cost (59.6%). As follow-up time increased, the total annual cost (beta=-2.07) and annual cost for DNA testing (beta=-1.03) decreased. The cost trajectory of the first two years of monitoring remained above the semi-annual follow-up strategy. After three years, the cost trajectory of monitoring, while reducing slightly, remained between the semi-annual and annual follow-up strategy trend lines. Conclusion: Due to high-patient numbers, the total cost of monitoring presents a large economic burden. Taking into consideration the generally benign nature of the disease; the length of intervals between outpatient hospital visits could be reviewed and alternative strategies implemented with the aim of reducing expenditure

Evaluation of biventricular function in patients with COVID-19 using speckle tracking echocardiography

A new infectious outbreak sustained by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now spreading all around the world. The aim of this study was to evaluate the prognostic value of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) in patients with coronavirus disease 2019 (COVID-19). In this prospective, single-center study, data were gathered from patients treated for COVID-19 between April 15 and April 30, 2020. Two-dimensional echocardiography (2-DE) and speckle tracking echocardiography (STE) images were obtained for all patients. Patients were divided into three groups: those with severe COVID-19 infection, those with non-severe COVID-19 infection, and those without COVID-19 infection (the control group). Data regarding clinical characteristics and laboratory findings were obtained from electronic medical records. The primary endpoint was in-hospital mortality. A total of 100 patients hospitalized for COVID-19 were included in this study. The mean age of the severe group (n = 44) was 59.1 +/- 12.9, 40% of whom were male. The mean age of the non-severe group (n = 56) was 53.7 +/- 15.1, 58% of whom were male. Of these patients, 22 died in the hospital. In patients in the severe group, LV-GLS and RV-LS were decreased compared to patients in the non-severe and control groups (LV-GLS: - 14.5 +/- 1.8 vs. - 16.7 +/- 1.3 vs. - 19.4 +/- 1.6, respectively [p < 0.001]; RV-LS: - 17.2 +/- 2.3 vs. - 20.5 +/- 3.2 vs. - 27.3 +/- 3.1, respectively [p < 0.001]). The presence of cardiac injury, D-dimer, arterial oxygen saturation (SaO2), LV-GLS (OR 1.63, 95% confidence interval [CI] 1.08-2.47; p = 0.010) and RV-LS (OR 1.55, 95% CI 1.07-2.25; p = 0.019) were identified as independent predictors of mortality via multivariate analysis. LV-GLS and RV-LS are independent predictors of in-hospital mortality in patients with COVID-19

Carbapenem-resistant Klebsiella pneumoniae outbreak in a COVID-19 intensive care unit; a case-control study

We analysed a carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak in the coronavirus disease (COVID) ICU. We retrospectively collected data from ICU records. We identified 25 cases between 12 November 2020 and 19 December 2020, and compared them to 42 controls present in the ICU during the same period. The presence of a femoral haemodialysis catheter was strongly associated with invasive CRKP infections (cases, 9 [36%]; controls, 0 [0%]; odds ratio [OR] 95% confidence intervals [CIs], 21 (5; 89)). We found a significant association between old age and CRKP infection with adverse outcomes. Sequence analysis revealed three distinct carbapenemase genes: bla(NDM-1), bla(OXA-48) and bla(KPC-2). We launched rectal swab sampling upon admission to the ICU, cohorted colonized patients and cases and conducted an intensive training programme for newly employed staff. This study revealed that the emergence and dissemination of CRKP in COVID ICUs were associated with increased adverse outcomes. The presence of a femoral haemodialysis catheter was a significant risk factor for CRKP infections