Monte Carlo Optimization Method Based QSAR Modeling of Placental Barrier Permeability.

Purpose: In order to ensure that drug administration is safe during pregnancy, it is crucial to have the possibility to predict the placental permeability of drugs in humans. The experimental method which is most widely used for the said purpose is in vitro human placental perfusion, though the approach is highly expensive and time consuming. Quantitative structure-activity relationship (QSAR) modeling represents a powerful tool for the assessment of the drug placental transfer, and can be successfully employed to be an alternative in in vitro experiments.

Mechanochemical Synthesis of TiO-CeO Mixed Oxides Utilized as a Screen-Printed Sensing Material for Oxygen Sensor.

TiO and CeO are well known as oxygen sensing materials. Despite high sensitivity, the actual utilization of these materials in gas detection remains limited. Research conducted over the last two decades has revealed synergistic effects of TiO-CeO mixed oxides that have the potential to improve some aspects of oxygen monitoring.

Correction: Cost-effectiveness of apixaban compared to other anticoagulants in patients with atrial fibrillation in the real-world and trial settings.

[This corrects the article DOI: 10.1371/journal.pone.

Preventive and Therapeutic Potential of Physical Exercise in Neurodegenerative Diseases.

The prevalence and incidence of age-related neurodegenerative diseases (NDDs) tend to increase along with the enhanced average of the world life expectancy. NDDs are a major cause of morbidity and disability, affecting the health care, social and economic systems with a significant impact. Despite the worldwide burden of NDDs and the ongoing research efforts to increase the underlying molecular mechanisms involved in NDD pathophysiologies, pharmacological therapies have been presenting merely narrow benefits.

Physical exercise and liver "fitness": Role of mitochondrial function and epigenetics-related mechanisms in non-alcoholic fatty liver disease.

Background: Modern lifestyles, especially high-caloric intake and physical inactivity, contribute to the increased prevalence of non-alcoholic fatty liver disease (NAFLD), which becomes a significant health problem worldwide. Lifestyle changes, however, affect not only parental generation, but also their offspring, reinforcing the need for efficient preventive approaches to deal with this disease. This transgenerational influence of phenotypes dependent on parents (particularly maternal) behaviours may open additional research avenues.

Phenotypic and genetic spectrum of patients with limb-girdle muscular dystrophy type 2A from Serbia.

Limb-girdle muscular dystrophy (LGMD) type 2A (calpainopathy) is an autosomal recessive disease caused by mutation in the gene. The aim of this study was to examine genetic and phenotypic features of Serbian patients with calpainopathy. The study comprised 19 patients with genetically confirmed calpainopathy diagnosed at the Neurology Clinic, Clinical Center of Serbia and the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia during a ten-year period.

Cost-effectiveness of apixaban compared to other anticoagulants in patients with atrial fibrillation in the real-world and trial settings.

Introduction: Randomized clinical trials (RCTs) and real-world data (RWD) in patients with atrial fibrillation have shown that-compared to vitamin K antagonists (VKAs)-non-VKA oral anticoagulants (NOACs) are at least as effective in the prevention of ischaemic stroke, while decreasing the risk of bleeding.

Objective: We aim to evaluate the cost-effectiveness of the NOAC apixaban versus other NOACs (dabigatran, edoxaban and rivaroxaban) and VKA, for stroke prevention in patients with atrial fibrillation by including the available data both from RCT and real-world analyses of all NOACs into one integrative previously published model.

Methods: The model was updated to the current Dutch healthcare situation.

Extended Treatment with Apixaban for Venous Thromboembolism Prevention in the Netherlands: Clinical and Economic Effects.

 Dutch guidelines advise extended anticoagulant treatment with direct oral anticoagulants or vitamin K antagonists for patients with idiopathic venous thromboembolism (VTE) who do not have high bleeding risk.  The aim of this study was to analyze the economic effects of extended treatment of apixaban in the Netherlands, based on an updated and adapted previously published model.  We performed a cost-effectiveness analysis simulating a population of 1,000 VTE patients.

Semi-rational design of cellobiose dehydrogenase for increased stability in the presence of peroxide.

Cellobiose dehydrogenase (CDH, EC 1.1.99.

Self-Paced Free-Running Wheel Mimics High-Intensity Interval Training Impact on Rats' Functional, Physiological, Biochemical, and Morphological Features.

Free-running wheel (FRW) is an animal exercise model that relies on high-intensity interval moments interspersed with low-intensity or pauses apparently similar to those performed in high-intensity interval training (HIIT). Therefore, this study, conducted over a 12-weeks period, aimed to compare functional, thermographic, biochemical and morphological skeletal and cardiac muscle adaptations induced by FRW and HIIT. Twenty-four male Wistar rats were assigned into three groups: sedentary rats (SED), rats that voluntarily exercise in free wheels (FRW) and rats submitted to a daily HIIT.

N-MEA Probes: Scooping Neuronal Networks.

In the current work, we introduce a brand new line of versatile, flexible, and multifunctional MEA probes, the so-called , or N-MEAs. Material choice, dimensions, and room for further upgrade, were carefully considered when designing such probes in order to cover the widest application range possible. Proof of the operation principle of these novel probes is shown in the manuscript via the recording of extracellular signals, such as action potentials and local field potentials from cardiac cells and retinal ganglion cells of the heart tissue and eye respectively.

Quality of life in adult patients with limb-girdle muscular dystrophies.

Although limb-girdle muscular dystrophies (LGMD) can cause permanent disability, to date there are no studies that examined quality of life (QoL) in these patients. Our aim was to evaluate QoL in patients with LGMD, and to identify the most significant predictors of QoL. The study comprised 46 patients with diagnosis of limb-girdle muscular weakness.

The cost-effectiveness and monetary benefits of dabigatran in the prevention of arterial thromboembolism for patients with non-valvular atrial fibrillation in the Netherlands.

Background: Atrial fibrillation (AF) causes a significant health and economic burden to the Dutch society. Dabigatran was proven to have at least similar efficacy and a similar or better safety profile when compared to vitamin K antagonists (VKAs) in preventing arterial thromboembolism in patients with AF.

Objective: To evaluate the cost-effectiveness and monetary benefit of dabigatran vs VKAs in Dutch patients with non-valvular AF.

Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.

The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage.

Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status.

Background: Intra-abdominal infection in secondary peritonitis drives as excessive production of inflammatory mediators and the development of systemic inflammatory response syndrome (SIRS) or sepsis. Finding a specific marker to distinguish SIRS from sepsis would be of immense clinical importance for the therapeutic approach. It is assumed that high-mobility group box 1 protein (HMGB1) could be such a marker.

Adoption of Biosimilar Infliximab for Rheumatoid Arthritis, Ankylosing Spondylitis, and Inflammatory Bowel Diseases in the EU5: A Budget Impact Analysis Using a Delphi Panel.

Introducing biosimilar infliximab for the treatment in rheumatology (rheumatoid arthritis and ankylosing spondylitis) and inflammatory bowel disease (Crohn's disease and ulcerative colitis) may reduce treatment costs associated with biologics. This study aimed to investigate the budget impact of adopting biosimilar infliximab in five European countries, considering that the budget impact includes the adoption of biosimilar infliximab and the availability of biologic alternatives such as vedolizumab, biosimilar etanercept, biosimilar rituximab, and other relevant factors. An existing budget impact model was adapted to forecast the budget impact in the UK, Germany, France, Spain, and Italy.

Improved Flavin-Based Catalytic Photooxidation of Alcohols through Intersystem Crossing Rate Enhancement.

The triplet excited-state formation efficiency in a flavin derivative was increased by the introduction of iodine into the molecular framework. The transient absorption measurements showed that the intersystem crossing rate was 1.1 × 10(10) s(-1), significantly faster than in the parent flavin compound.

Budget Impact of Increasing Market Share of Patient Self-Testing and Patient Self-Management in Anticoagulation.

Background: Patient self-testing (PST) and/or patient self-management (PSM) might provide better coagulation care than monitoring at specialized anticoagulation centers. Yet, it remains an underused strategy in the Netherlands.

Methods: Budget-impact analyses of current and new market-share scenarios of PST and/or PSM compared with monitoring at specialized centers were performed for a national cohort of 260,338 patients requiring long-term anticoagulation testing.

Multivariate Meta-Analysis of Preference-Based Quality of Life Values in Coronary Heart Disease.

Background: There are numerous health-related quality of life (HRQol) measurements used in coronary heart disease (CHD) in the literature. However, only values assessed with preference-based instruments can be directly applied in a cost-utility analysis (CUA).

Objective: To summarize and synthesize instrument-specific preference-based values in CHD and the underlying disease-subgroups, stable angina and post-acute coronary syndrome (post-ACS), for developed countries, while accounting for study-level characteristics, and within- and between-study correlation.

Changes Needed in the Classification of Anxiety Disorders in Childhood: Options for ICD-11.

Considering the intensive preparation of the 11th revision of the International Classification of Diseases (ICD-11), we discussed the justification of the existing classification of emotional disorders with onset specific to childhood. This paper presents the citations from the ICD-10 (F93 block) and the authors' comments as a critical review of the justification of further existence of emotional disorders with onset specific to childhood as a separate block in ICD-11 classification. We concluded that the block F93 is insufficiently defined and should be completely changed or removed from the ICD-11 classification.

Cost-Effectiveness of Dabigatran Compared to Vitamin-K Antagonists for the Treatment of Deep Venous Thrombosis in the Netherlands Using Real-World Data.

Background: Vitamin-K antagonists (VKAs) present an effective anticoagulant treatment in deep venous thrombosis (DVT). However, the use of VKAs is limited because of the risk of bleeding and the necessity of frequent and long-term laboratory monitoring. Therefore, new oral anticoagulant drugs (NOACs) such as dabigatran, with lower rates of (major) intracranial bleeding compared to VKAs and not requiring monitoring, may be considered.

Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands.

Background: Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs.

Economic evaluation of primary prevention of cardiovascular diseases in mild hypertension: a scenario analysis for the Netherlands.

Background: In the Netherlands, antihypertensive treatment for patients with mild hypertension is recommended if the 10-year cardiovascular disease (CVD) risk exceeds 20%. Recent evidence suggests that lifelong CVD risk estimates might be more informative than 10-year ones. In addition, the cost of antihypertensive treatment in the Netherlands has decreased during the last decade.

A systematic review on the application of cardiovascular risk prediction models in pharmacoeconomics, with a focus on primary prevention.

Background: Long-term trials on the effectiveness of pharmacological treatment for primary cardiovascular disease prevention are scant. For that reason risk prediction models are used as a tool to project changes in cardiovascular disease incidence due to changes in risk factor levels observed in short-term randomized clinical trials. In this article, we summarize the literature on the application of these risk models in pharmacoeconomic studies for primary cardiovascular disease prevention interventions in high-income countries.