Applications of trimetallic nanomaterials as Non-Enzymatic glucose sensors.

OBJECTIVE: This article critically reviews recent research on the use of trimetallic nanomaterials for the fabrication of non-enzymatic glucose sensors (NEGS), also known as fourth-generation glucose sensors (FGGS). SIGNIFICANCE: Diabetes is a prevalent chronic disease worldwide, and glucose monitoring is crucial for its management. However, conventional enzymatic glucose sensors suffer from several technological drawbacks, and there is a need to develop new-generation glucose sensors that can overcome these limitations. NEGS, particularly those composed of trimetallic nanocomposites, have demonstrated promising results in terms of improved shelf life, higher sensitivity, and simplicity of operation during glucose measurement. METHODS: In this review, we discuss the different trimetallic nanomaterials developed and used by researchers in recent years for glucose detection, including their mechanisms of action. We also provide a brief discussion of the advantages and disadvantages of FGGS-based trimetallic nanomaterials, as well as the industrial challenges in this area of research. RESULTS: Trimetallic nanomaterials for FGGS have shown excellent reproducibility and high stability, making them suitable for continuous glucose monitoring. The different types of trimetallic nanomaterials have varying sensing properties, and their performance can be tuned by controlling their synthesis parameters. CONCLUSION: Trimetallic nanomaterials are a promising avenue for the development of FGGS, recent research has demonstrated their potential for glucose monitoring. However, there are still some challenges that need to be addressed before their widespread adoption, such as their long-term stability and cost-effectiveness. Further research in this area is needed to overcome these challenges and to develop commercially viable FGGS for diabetes management.

Comparing the complexity of written and molecular symbolic systems.

Symbolic systems (SSs) are uniquely products of living systems, such that symbolism and life may be inextricably intertwined phenomena. Within a given SS, there is a range of symbol complexity over which signaling is functionally optimized. This range exists relative to a complex and potentially infinitely large background of latent, unused symbol space. Understanding how symbol sets sample this latent space is relevant to diverse fields including biochemistry and linguistics. We quantitatively explored the graphic complexity of two biosemiotic systems: genetically encoded amino acids (GEAAs) and written language. Molecular and graphical notions of complexity are highly correlated for GEAAs and written language. Symbol sets are generally neither minimally nor maximally complex relative to their latent spaces, but exist across an objectively definable distribution, with the GEAAs having especially low complexity. The selection pressures guiding these disparate systems are explicable by symbol production and disambiguation efficiency. These selection pressures may be universal, offer a quantifiable metric for comparison, and suggest that all life in the Universe may discover optimal symbol set complexity distributions with respect to their latent spaces. If so, the "complexity" of individual components of SSs may not be as strong a biomarker as symbol set complexity distribution.

Long-term outcomes following catheter ablation versus medical therapy in patients with persistent atrial fibrillation and heart failure with reduced ejection fraction.

AIMS: The ARC-HF and CAMTAF trials randomized patients with persistent atrial fibrillation (AF) and heart failure (HF) to early routine catheter ablation (ER-CA) versus pharmacological rate control (RC). After trial completion, delayed selective catheter ablation (DS-CA) was performed where clinically indicated in the RC group. We hypothesized that ER-CA would result in a lower risk of cardiovascular hospitalization and death versus DS-CA in this population. METHODS AND RESULTS: Overall, 102 patients were randomized (age 60 ± 11 years, left ventricular ejection fraction [LVEF] 31 ± 11%): 52 to ER-CA and 50 to RC. After 12 months, patients undergoing ER-CA had improved self-reported symptom scores, lower New York Heart Association class (i.e. better functional capacity), and higher LVEF compared to patients receiving RC alone. During a median follow-up of 7.8 (interquartile range 3.9-9.9) years, 27 (54%) patients in the RC group underwent DS-CA and 34 (33.3%) patients died, including 17 (32.7%) randomized to ER-CA and 17 (34.0%) randomized to RC. Compared with DS-CA, a strategy of ER-CA exhibited similar risk of all-cause mortality (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.44-1.77, p = 0.731) and combined all-cause mortality or cardiovascular hospitalization (aHR 0.80, 95% CI 0.43-1.47, p = 0.467). However, analyses according to treatment received suggested an association between CA and improved outcomes versus RC (all-cause mortality: aHR 0.43, 95% CI 0.20-0.91, p = 0.028; all-cause mortality/cardiovascular hospitalization: aHR 0.48, 95% CI 0.24-0.94, p = 0.031). CONCLUSIONS: In patients with persistent AF and HF, ER-CA produces similar long-term outcomes to a DS-CA strategy. The association between CA as a treatment received and improved outcomes means there is still a lack of clarity regarding the role of early CA in selected patients. Randomized trials are needed to clarify this question.

Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.

OBJECTIVE: To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms. DESIGN: Prospective, open-label, multicentre, stratified, randomised clinical trial. SETTING: Five hospitals in UK and India, from September 2020 to May 2021. PARTICIPANTS: Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset. INTERVENTION: Leflunomide 100 mg/day (3 days) followed by 10-20 mg/day (7 days) added to standard care. PRIMARY OUTCOMES: The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days. RESULTS: Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4-8) compared with 7 days (IQR 5-10) in SOC group (p=0.047). CONCLUSION: Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients. TRIAL REGISTRATION NUMBERS: EudraCT Number: 2020-002952-18, NCT05007678.

Autoptic identification of disseminated mucormycosis in a young male presenting with cerebrovascular event, multi-organ dysfunction and COVID-19 infection.

Among the secondary fungal infections in Coronavirus-19 (COVID-19) infection, Aspergillosis has been reported more often than Mucormycosis. Disseminated mucormycosis is almost always a disease of severely immunosuppressed hosts. We report a young obese Asian male who was admitted with an acute anterior cerebral artery (ACA) territory infarct and severe COVID-19 pneumonitis to the intensive care unit (ICU). He had a complicated stay with recurrent episodes of vasoplegic shock and multi-organ dysfunction. At autopsy, he was confirmed to have disseminated mucormycosis. We believe this to be the first documented case of disseminated mucormycosis in an immunocompetent host with COVID-19 infection. The lack of sensitive non-invasive modalities and biomarkers to diagnose mucormycosis, along with the extremely high mortality in untreated cases, present a unique challenge to clinicians dealing with critically ill patients with COVID-19.

Surveillance and Molecular Identification of Acanthamoeba and Naegleria Species in Two Swimming Pools in Alexandria University, Egypt.

BACKGROUND: Swimming in contaminated water was reported to be associated with Acanthamoeba and N. fowleri human infections. The present study was carried out with the aim of isolation and identification of the different species of Acanthamoeba and Naegleria from two swimming pools in Alexandria University. METHODS: Samples were collected from the swimming pools of Alexandria University Stadium and Faculty of Agriculture-Alexandria University during the period from May 2012 to April 2013. RESULTS: Free-living amoebae were prevalent in the collected samples. Molecular characterization confirmed the identity of ten Acanthamoeba isolates and seven Naegleria isolates. Acanthamoeba T3, T4, T5, T11 and T15 genotypes were identified. Acanthamoeba T4 was the most prevalent genotype. CONCLUSION: The relatively high prevalence of Acanthamoeba, especially genotype T4, indicates the presence of a health hazard to swimmers particularly those wearing contact lenses. Naegleria fowleri was not found during the present study.