Notes

[Fast determination of mineral factors inside grain flour simply by near-infrared spectroscopy].
The efficacy of pharmacotherapy is limited by the occurrence of adverse drug reactions and the interactions between several drugs in polypharmacy, which are difficult to predict. Taking into account the complex mode of action of drugs, including their specific profiles of side effects, high demands are placed on the medical information with respect to a proper and complete clarification of the risks and alternative information under the precept of patient-oriented comprehensibility; however, these requirements can hardly ever be fulfilled in everyday medical practice. This article discusses the practical limitations of the information provided prior to the initiation and monitoring of drug therapy on the basis of selected current case law. In particular, the potential for conflict between the Patients' Rights Act and the so-called right to non-knowledge is highlighted.The inhibition of glycerol permeation via human aquaporin-10 (hAQP10) by organometallic gold complexes has been studied by stopped-flow fluorescence spectroscopy, and its mechanism has been described using molecular modelling and atomistic simulations. The most effective hAQP10 inhibitors are cyclometalated Au(III) C^N compounds known to efficiently react with cysteine residues leading to the formation of irreversible C-S bonds. Functional assays also demonstrate the irreversibility of the binding to hAQP10 by the organometallic complexes. The obtained computational results by metadynamics show that the local arylation of Cys209 in hAQP10 by one of the gold inhibitors is mapped into a global change of the overall free energy of glycerol translocation across the channel. Our study further pinpoints the need to understand the mechanism of glycerol and small molecule permeation as a combination of local structural motifs and global pore conformational changes, which are taking place on the scale of the translocation process and whose study, therefore, require sophisticated molecular dynamics strategies.
The Global Burden of Disease (GBD) study has generated a wealth of data on death and disability outcomes in Europe. It is important to identify the disease burden that is attributable to risk factors and, therefore, amenable to interventions. This paper reports the burden attributable to risk factors, in deaths and disability-adjusted life years (DALYs), in the 28 European Union (EU) countries, comparing exposure to risks between them, from 2007 to 2017.

Retrospective descriptive study, using secondary data from the GBD 2017 Results Tool. For the EU-28 and each country, attributable (all-cause) age-standardized death and DALY rates, and summary exposure values are reported.

In 2017, behavioural and metabolic risk factors showed a higher attributable burden compared with environmental risks, with tobacco, dietary risks and high systolic blood pressure standing out. While tobacco and air quality improved significantly between 2007 and 2017 in both exposure and attributable burden, others such as childhoodpposite side, some concerning cases must be highlighted (i.e. tobacco in Bulgaria, Latvia and Estonia or drug use in Czech Republic).To determine whether the cause of cardiomyopathy affects outcomes in patients who undergo continuous-flow left ventricular assist device support, we compared postimplant adverse events and survival between patients with ischemic and nonischemic cardiomyopathy. The inclusion criteria for the ischemic group were a history of myocardial infarction or revascularization (coronary artery bypass grafting or percutaneous coronary intervention), ≥75% stenosis of the left main or proximal left anterior descending coronary artery, or ≥75% stenosis of ≥2 epicardial vessels. From November 2003 through March 2016, 526 patients underwent device support 256 (48.7%) in the ischemic group and 270 (51.3%) in the nonischemic group. The ischemic group was older (60.0 vs 50.0 yr), included more men than women (84.0% vs 72.6%), and had more comorbidities. More patients in the nonischemic group were able to have their devices explanted after left ventricular recovery (5.9% vs 2.0%; P=0.02). More patients in the ischemic group had gastrointestinal bleeding (31.2% vs 22.6%; P=0.03), particularly from arteriovenous malformations (20.7% vs 11.9%; P=0.006) and ulcers (16.4% vs 9.3%; P=0.01). Kaplan-Meier analysis revealed no difference in overall survival between groups (P=0.24). Older age, previous sternotomy, higher total bilirubin level, and concomitant procedures during device implantation independently predicted death (P ≤0.03), whereas cause of heart failure did not (P=0.08). Despite the similarity in overall survival between groups, ischemic cardiomyopathy was associated with more frequent gastrointestinal bleeding. This information may help guide the care of patients with ischemic cardiomyopathy who receive continuous-flow left ventricular assist device support.
Cadmium (Cd) induces reactive oxygen species (ROS)-mediated hepatocyte apoptosis and consequential liver disorders. This study aimed to investigate the effect of magnesium isoglycyrrhizinate (MgIG) on Cd-induced hepatotoxicity.

L02 and AML-12 cells were used to study MgIG hepatoprotective effects. Cd-evoked apoptosis, ROS and protein phosphatase 2A (PP2A)/c-Jun N-terminal kinase (JNK) cascade disruption were analysed by cell viability assay, 6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, ROS imaging and Western blotting. Pharmacological and genetic approaches were used to explore the mechanisms.

We show that MgIG attenuated Cd-evoked hepatocyte apoptosis by blocking JNK pathway. Pre-treatment with SP600125 or ectopic expression of dominant-negative c-Jun enhanced MgIG's anti-apoptotic effects. Further investigation found that MgIG rescued Cd-inactivated PP2A. Inhibition of PP2A activity by okadaic acid attenuated the MgIG's inhibition of the Cd-stimulated JNK pathway and apoptosis; in contrast, overexpression of PP2A strengthened the MgIG effects. In addition, MgIG blocked Cd-induced ROS generation. Eliminating ROS by N-acetyl-l-cysteine abrogated Cd-induced PP2A-JNK pathway disruption and concurrently reinforced MgIG-conferred protective effects, which could be further slightly strengthened by PP2A overexpression.

Our findings indicate that MgIG is a promising hepatoprotective agent for the prevention of Cd-induced hepatic injury by mitigating ROS-inactivated PP2A, thus preventing JNK activation and hepatocyte apoptosis.
Our findings indicate that MgIG is a promising hepatoprotective agent for the prevention of Cd-induced hepatic injury by mitigating ROS-inactivated PP2A, thus preventing JNK activation and hepatocyte apoptosis.Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis modecO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.
This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.The main objective of this study was to evaluate the effect of peripartal administration of a commercially available nonspecific immune stimulant (mycobacterium cell wall fraction; MCWF [Amplimune, NovaVive Inc., Napanee, ON, Canada]) on the incidence of disease during early lactation and subsequent fertility of dairy cows. A second objective was to characterize the dynamics of circulating white blood cells (WBC) and metabolic markers following treatment administration. Cows in an United States Department of Agriculture (USDA) organic-certified dairy herd were blocked by parity and, based on sequential calving dates, randomly assigned to receive two injections (5 mL s.c.) of either a placebo (saline solution) as a control (CON; n = 71) or MCWF (n = 65) at enrollment (7 d before expected calving) and within 24 h after calving. Blood samples were collected from a subsample of the study population (MCWF = 16; CON = 18) for WBC count at enrollment, at day 2 post enrollment, and at days 1, 3, 7, and 14 after calviy MCWF administration pregnancy at first AI and pregnancy at 100 and 150 DIM were greater in MCWF than in CON (35.6% vs. 19.2%; 51.1% vs. 25.0%; and 64.4% vs. 40.4%, respectively). Overall, median intervals from calving to pregnancy were 90 vs. BTK inhibitor 121 d in MCWF and CON cows, respectively. No treatment effects on the dynamics of circulating WBC or in postpartum metabolic status were established. No differences for milk yield or for the proportion of cows that survived up to 305 DIM were determined, although cows in MCWF left the herd earlier than cows in CON. In conclusion, incidence risks of metritis and mastitis in early lactation were smaller in cows receiving MCWF, whereas the incidence risk of respiratory disease was smaller in CON. Fertility significantly improved in MCWF compared with CON cows. As this study was performed in an organic-certified dairy, specific health and reproductive management practices may affect the external validity of the current findings.
Smartwatch electrocardiograms (ECGs) could facilitate the detection of sudden cardiac arrest (SCA)-associated abnormalities. We evaluated the feasibility of using smartwatch-derived ECGs for detecting SCA-associated abnormalities in young adults and its agreement with 12-lead ECGs.

Twelve-lead and Apple Watch ECGs were registered in 155 healthy volunteers and 67 patients aged 18-45 years with diagnosis and ECG signs of long-QT syndrome (n = 10), Brugada syndrome (n = 12), ventricular pre-excitation (n = 19), hypertrophic cardiomyopathy (HCM, n = 13), and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC/D, n = 13). Cardiologists separately analysed 12-lead ECGs and the smartwatch ECGs taken from the left wrist (AW-I) and then from chest positions V1, V3, and V6 (AW-4). Compared with AW-I, AW-4 improved the classification of ECGs as 'abnormal', increasing the sensitivity from 64% to 89% (P < 0.01). Pre-excitation was detected in most cases using AW-I (sensitivity 89%) and in all cases using AW-4 (sensitivity 100%, P = 0.48 compared with AW-I, specificity 100% for both). Brugada was missed using AW-I but was detected in 11/12 patients using AW-4 (sensitivity 92%, specificity 100%, P = 0.003). Long QT was detected in 8/10 cases using AW-I (sensitivity 80%, specificity 100%) and in 9 patients using AW-4 (sensitivity 90%, specificity 100%, P > 0.99). Hypertrophic cardiomyopathy was correctly suspected using AW-I and AW-4 (sensitivity 92% and 85%, specificity 85%, and 100%, P > 0.99). AW-I was mostly (62%) considered normal in ARVC/D whereas AW-4 was useful in suspecting ARVC/D (100% sensitivity, 99% specificity, P = 0.004).

Detection of SCA-associated ECG abnormalities (pre-excitation, Brugada patterns, long QT, and signs suggestive of HCM and ARVC/D) is possible with an ECG smartwatch.
Detection of SCA-associated ECG abnormalities (pre-excitation, Brugada patterns, long QT, and signs suggestive of HCM and ARVC/D) is possible with an ECG smartwatch.
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