A Facile Approach to the Hydrothermal Synthesis of Silica Nanoparticle/Carbon Nanostructure Luminescent Composites

Luminescent carbon nanostructures (CNSs) have been intensively researched, but there is still no consensus on a fundamental understanding of their structure and properties that limits their potential applications. In this study, we developed a facile approach to the synthesis of luminescent composite SiO₂ nanoparticles/CNSs by the targeted formation of a molecular fluorophore, as the significant luminescent component of CNSs, on the surface of a silica matrix during a one-stage hydrothermal synthesis. Silica nanoparticles were synthesized by reverse microemulsion and used as a matrix for luminescent composites. The as-prepared silica nanoparticles had a functional surface, a spherical shape, and a narrow size distribution of about 29 nm. One-stage hydrothermal treatment of citric acid and modified silica nanoparticles made it possible to directly form the luminescent composite. The optical properties of composites could be easily controlled by changing the hydrothermal reaction time and temperature. Thus, we successfully synthesized luminescent composites with an emission maximum of 450 nm, a quantum yield (QY) of 65 ± 4%, and an average size of ~26 nm. The synthesis of fluorophore doped composite, in contrast to CNSs, makes it possible to control the shape, size, and surface functionality of particles and allows for avoiding difficult and time-consuming fractionation steps.     

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients

BackgroundExtracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time.MethodsThis retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019.ResultsECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87–0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock.ConclusionsIn-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively.     

The effects of voluntary contraction effort on quadriceps femoris electromyogram median frequency in humans: a muscle and sex comparison

The purpose of this study was to examine the effect of voluntary contraction efforts on the median frequency (f _med) of the electromyogram (EMG) recorded from the quadriceps femoris muscle in healthy men and women. A group of 30 healthy volunteers (15 men, 15 women) were assessed for EMG activity of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) muscles during isometric contractions with the knee at 60° flexion. Subjects performed a series of 5 s maximal voluntary isometric contractions that anchored the perceptual range with a "10" on a 10-point scale. Sub-maximal isometric contractions were then separately performed at the following perceived effort levels on the 10-point scale: 1, 2, 3, 4, 5, 6, 7, 8 and 9, in a random order. Subjects were instructed to maintain the contraction at each perceived level of effort for 5 s. The f _med of the three muscles was assessed using a power spectrum analysis performed over 11 consecutive, 512 ms, epochs overlapping each other by half their length during the middle 3 s of each contraction. The f _med for each of the 11 epochs was then determined for each muscle, followed by calculation of the means and normalized coefficients of variation [(standard deviation/mean)×100%] for each contraction. The results demonstrated that the mean f _med of VL was significantly greater than those of the other two muscles, and that f _med of RF was significantly greater than that of VM. The VL muscle demonstrated a significant increase in mean f _med across the contraction efforts, compared to the VM and RF muscles that displayed a significant decrease. The men displayed significantly higher f _med values for the VM muscle than did the women, as well as showing a significantly greater increase across the contraction efforts for the VL muscle. The variability of f _med was shown to be significantly higher for the VM muscle, compared to the VL and RF muscles. The findings of this study suggest that the f _med statistic is most sensitive to contraction intensity efforts for the VL muscle, and that men display significantly higher values for the VL and VM muscles, compared to women. Electronic Publication     

Chronic biopsy proven post‐COVID myoendocarditis with SARS‐Cov‐2 persistence and high level of antiheart antibodies

PurposeTo study the clinical signs and mechanisms (viral and autoimmune) of myoendocarditis in the long‐term period after COronaVIrus Disease 2019 (COVID‐19).MethodsFourteen patients (nine male, 50.1 ± 10.2 y.o.) with biopsy proven post‐COVID myocarditis were observed. The diagnosis of COVID‐19 was confirmed by IgG seroconversion. The average time of admission after COVID‐19 was 5.5 [2; 10] months. An endomyocardial biopsy (EMB) of the right ventricle was obtained. The biopsy analysis included polymerase chain reaction diagnosis of viral infection, morphological, immunohistochemical (IHC) examination with antibodies to CD3, CD45, CD68, CD20, SARS‐Cov‐2 spike, and nucleocapsid antigens. Coronary atherosclerosis was ruled out in all patients over 40 years.ResultsThe new cardiac symptoms (congestive heart failure 3–4 New York Heart Association class with severe right ventricular involvement, various rhythm, and conduction disturbances) appeared 1–5 months following COVID‐19. Magnetic resonance imaging showed disseminated or focal subepicardial and intramyocardial late gadolinium enhancement, hyperemia, edema, and increased myocardial native T1 relaxation time. Antiheart antibodies levels were increased 3–4 times in 92.9% of patients. The mean left ventricular (LV) ejection fraction (EF) was 28% (24.5; 37.8). Active lymphocytic myocarditis was diagnosed in 12 patients, eosinophilic myocarditis in two patients. SARS‐Cov‐2 RNA was detected in 12 cases (85.7%), in association with parvovirus B19 DNA—in one. Three patients had also endocarditis (infective and nonbacterial, with parietal thrombosis). As a result of steroid and chronic heart failure therapy, the EF increased to 47% (37.5; 52.5).ConclusionsCOVID‐19 can lead to long‐term severe post‐COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post‐COVID myoendocarditis.     

A Review of: “ Handbook of Adaptive Designs in Pharmaceutical and Clinical Development,by A. Pong and S.-C. Chow (Eds.)”

In practice, there exist many disease processes with three ordinal disease classes; for example, in the detection of Alzheimer’s disease (AD) a patient can be classified as healthy (disease-free stage), mild cognitive impairment (early disease stage), or AD (full disease stage). The treatment interventions and effectiveness of such disease processes will depend on the disease stage. Therefore, it is important to develop diagnostic tests with the ability to discriminate between the three disease stages. Measuring the overall ability of diagnostic tests to discriminate between the three classes has been discussed extensively in the literature. However, there has been little proposed on how to select clinically meaningful thresholds for such diagnostic tests, except for a method based on the generalized Youden index by Nakas et al. (2010). In this article, we propose two new criteria for selecting diagnostic thresholds in the three-class setting. The numerical study demonstrated that the proposed methods may provide thresholds with less variability and more balance among the correct classification rates for the three stages. The proposed methods are applied to two real examples: the clinical diagnosis of AD from the Washington University Alzheimer’s Disease Research Center and the detection of liver cancer (LC) using protein segments.     

Relationships between inflammation,hemodynamic function and RAAS in longstanding type 1 diabetes and diabetic kidney disease

The renin angiotensin aldosterone system (RAAS) is associated with renal disease and inflammation in a diabetes setting, however, little is known about the implicated mechanisms in individuals with long standing diabetes. Accordingly, our aim was to perform an observational study to quantify urinary excretion of inflammatory biomarkers in participants with long standing type 1 diabetes (T1D) (with and without diabetic kidney disease [DKD]) and controls, at baseline and in response to RAAS activation. GFR_INULIN, ERPF_PAH, and 42 urine inflammatory biomarkers were measured in 74 participants with T1D for ≥50 years (21 with DKD and 44 without DKD [DKD resistors]) and 73 healthy controls. Additionally, inflammatory biomarkers were measured before and after an angiotensin II infusion (ANGII, 1 ng?kg^?1?min^?1). Significantly lower urinary excretion of cytokines (IL-18, IL-1RA, IL-8), chemokines (MCP1, RANTES) and growth factors (TGF-α, PDGFAA, PDGFBB, VEGF-A) was observed in participants with T1D at baseline compared to controls. Urinary IL-6 was higher in DKD than in DKD resistors in an exploratory analysis unadjusted for multiple comparisons. In T1D only, lower GFR_INULIN correlated with greater excretion of proinflammatory biomarkers (IL-18, IP-10, & RANTES), growth factors (PDGF-AA & VEGFAA), and chemokines (eotaxin & MCP-1). ANGII increased 31 of 42 inflammatory biomarkers in T1D vs controls (p < 0.05), regardless of DKD resistor status. In conclusion, lower GFR and intra-renal RAAS activation were associated with increased inflammation even after longstanding T1D. The increased urinary IL-6 in patients with DKD requires further investigation to determine whether IL-6 is a candidate protective biomarker for prognostication or targeted therapy in DKD.     

Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT Trial.

AIMS: We sought to determine risk models for predicting early and late stroke in a large cohort of high-risk post-myocardial infarction (MI) patients. METHODS AND RESULTS: We prospectively analysed data from 14 703 patients in the VALIANT trial with acute MI complicated by heart failure, left ventricular (LV) systolic dysfunction, or both. Patients were randomized 0.5-10 days after acute MI to valsartan, captopril, or their combination. We evaluated risk factors for early (<45 days) and late (>45 days) stroke by using multivariable Cox proportional hazards regression analyses with stepwise variable selection techniques applied to 92 pre-specified potential predictor variables. After randomization, 463 (3.2%) patients had fatal (n = 124) or non-fatal (n = 339) strokes, with 134 strokes occurring in the first 45 days. The strokes were classified as ischaemic (348), haemorrhagic (40), or of indeterminate cause (75). Estimated glomerular filtration rate and heart rate when in sinus rhythm were the most powerful predictors of early stroke (<45 days after MI), whereas diastolic blood pressure (DBP) >90 mmHg, prior stroke, and atrial fibrillation (AF) were the most powerful predictors of stroke overall. Ejection fraction and sex were not predictive of stroke in this cohort. CONCLUSION: Among high-risk patients presenting with MI but without initial neurological symptoms, the risk of stroke 6 weeks thereafter is 0.94% (95% CI 0.78-1.09). Of the most powerful baseline predictors of stroke, DBP and AF are amenable to therapeutic interventions and thus merit special attention in these patients.     

Sex differences in neuropathic pain in longstanding diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

Aim

Neuropathy and neuropathic pain are common complications of type 1 diabetes (T1D). We aimed to determine if sex-specific differences in neuropathic pain are present in adults with longstanding T1D.