Prescription versus over-the-counter venotonics: HPLC-DAD and static digestive model simulation comparison.

Background: Venotonics are a class of therapeutically active molecules that have vaso-protective effects. They are used to alleviate venous diseases and disorders, particularly venous insufficiency. We compared the composition of prescription versus over-the-counter (OTC) venotonics using high-performance liquid chromatography with UV detection (HPLC-DAD) and simulating their digestion using a static digestive model.

Evaluation of Cytotoxicity of the Dental Materials TheraCal LC, TheraCal PT, ApaCal ART and Biodentine Used in Vital Pulp Therapy: In Vitro Study.

(1) Background: The aim of this study was to compare the cytotoxicity of selected resin-modified materials used in direct contact with the dental pulp (TheraCal LC, TheraCal PT, and ApaCal ART) with calcium silicate cement (Biodentine). (2) Methods: The mouse fibroblast Balb/3T3 cell line and the extracts of tested materials in four concentrations were used for the testing. An MTT assay was performed in three independent experiments with six replicates for each concentration of tested material.

Alemtuzumab treatment for multiple sclerosis in Austria: An observational long-term outcome study.

Background/objective: Observational real-world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease-modifying therapy (DMT) usage in multiple sclerosis (MS).

Methods: Data retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6-month confirmed progression independent of relapse activity (PIRA; ≥ 0.5-point Expanded Disability Status Scale (EDSS) score increase), 6-month confirmed disability improvement (CDI; ≥ 0.

CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

Background: 'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy.

Fluorinated cGAMP analogs, which act as STING agonists and are not cleavable by poxins: Structural basis of their function.

The cGAS-STING pathway is a crucial part of innate immunity; it serves to detect DNA in the cytoplasm and to defend against certain cancers, viruses, and bacteria. We designed and synthesized fluorinated carbocyclic cGAMP analogs, MD1203 and MD1202D (MDs), to enhance their stability and their affinity for STING. These compounds demonstrated exceptional activity against STING.

Prognostic Properties of the GOLD 2023 Classification System.

Introduction: Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published an update on the Global Strategy for Prevention, Diagnosis and Management of COPD, introducing a new classification of chronic obstructive pulmonary disease (COPD). Our aim was to assess the prognostic value of the new GOLD classification system in comparison with the previous GOLD classification systems (GOLD stages I-IV and GOLD groups A-D) and the BODE index.

Methods: We used the data of 784 patients with COPD from the Czech Multicenter Research Database of COPD.

The Short-Term Antibacterial Activity of Three Selected Endodontic Sealers against Bacterial Culture.

(1) Background: Microorganisms originating from the microflora of the oral cavity are the main cause of the inflammatory diseases of the dental pulp and periapical periodontium, as well as the failure of endodontic treatment. The subsequent root canal treatment is not able to remove all the pathogens, and a small number of viable bacteria remain in the dentine tubules, which must be sealed by endodontic sealers. These sealers should have at least a bacteriostatic effect to prevent the remaining bacteria from reproducing.

Enzymatic Synthesis of 3'-5', 3'-5' Cyclic Dinucleotides, Their Binding Properties to the Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations.

The 3'-5', 3'-5' cyclic dinucleotides (3'3'CDNs) are bacterial second messengers that can also bind to the stimulator of interferon genes (STING) adaptor protein in vertebrates and activate the host innate immunity. Here, we profiled the substrate specificity of four bacterial dinucleotide synthases from (DncV), (btDisA), (dgcZ), and (tDGC) using a library of 33 nucleoside-5'-triphosphate analogues and then employed these enzymes to synthesize 24 3'3'CDNs. The STING affinity of CDNs was evaluated in cell-based and biochemical assays, and their ability to induce cytokines was determined by employing human peripheral blood mononuclear cells.

The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders.

The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge.

Synthesis and Biological Evaluation of Phosphoester and Phosphorothioate Prodrugs of STING Agonist 3',3'-c-Di(2'F,2'dAMP).

Cyclic dinucleotides (CDNs) are second messengers that bind to the stimulator of interferon genes (STING) and trigger the expression of type I interferons and proinflammatory cytokines. Here we evaluate the activity of 3',3'-c-di(2'F,2'dAMP) and its phosphorothioate analogues against five STING allelic forms in reporter-cell-based assays and rationalize our findings with X-ray crystallography and quantum mechanics/molecular mechanics calculations. We show that the presence of fluorine in the 2' position of 3',3'-c-di(2'F,2'dAMP) improves its activity not only against the wild type (WT) but also against REF and Q STING.

The Relation Between Clinical Phenotypes, GOLD Groups/Stages and Mortality in COPD Patients - A Prospective Multicenter Study.

Introduction: The concept of phenotyping emerged, reflecting specific clinical, pulmonary and extrapulmonary features of each particular chronic obstructive pulmonary disease (COPD) case. Our aim was to analyze prognostic utility of: "Czech" COPD phenotypes and their most frequent combinations, "Spanish" phenotypes and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages + groups in relation to long-term mortality risk.

Methods: Data were extracted from the Czech Multicenter Research Database (CMRD) of COPD.

Peripheral neuropathy due to neuroborreliosis: Insensitivity for CXCL13 as early diagnostic marker.

The case of a 69-year-old woman with peripheral neuropathy caused by Lyme neuroborreliosis (LNB) in an endemic region in Eastern Austria is reported. The patient had noticed transient numbness of her left leg. On initial examination, she had patchy sensory disturbances of the left lower leg, but ancillary examinations of nerve conduction and cerebrospinal fluid (CSF), including the B-cell chemokine CXCL13, were normal.

Ligand Strain and Its Conformational Complexity Is a Major Factor in the Binding of Cyclic Dinucleotides to STING Protein.

STING (stimulator of interferon genes) is a key regulator of innate immunity that has recently been recognized as a promising drug target. STING is activated by cyclic dinucleotides (CDNs) which eventually leads to expression of type I interferons and other cytokines. Factors underlying the affinity of various CDN analogues are poorly understood.

Feedback-Based Learning of Timing in Attention-Deficit/Hyperactivity Disorder and Neurofibromatosis Type 1.

Objective: Patients with Neurofibromatosis Type 1 (NF1) frequently display symptoms resembling those of Attention Deficit/Hyperactivity Disorder (ADHD). Importantly, these disorders are characterised by distinct changes in the dopaminergic system, which plays an important role in timing performance and feedback-based adjustments in timing performance. In a transdiagnostic approach, we examine how far NF1 and ADHD show distinct or comparable profiles of timing performance and feedback-based adjustments in timing.

Correction: Diagnostic value of partial exome sequencing in developmental disorders.

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

Introducing a new prognostic instrument for long-term mortality prediction in COPD patients: the CADOT index.

Objectives: The BODE (BMI, Obstruction - FEV, Dyspnoea - mMRC, Exercise - 6-MWT) and the ADO (Age, Dyspnoea - mMRC, Obstruction - FEV) indices are widely used prognosis assessment tools for long-term mortality prediction in COPD patients but subject to limitations for use in daily clinical practice. The aim of this research was to construct a prognostic instrument that prevents these limitations and which would serve as a complementary prognostic tool for clinical use in these patients.

Methods And Participants: The data of 699 COPD subjects were extracted from the Czech Multicentre Research Database (CMRD) of COPD patients (the derivation cohort) and analysed to identify factors associated with the long-term risk of mortality.

The genotoxic effects in the leukocytes of workers handling nanocomposite materials.

The extensive development of nanotechnologies and nanomaterials poses a number of questions to toxicologists about the potential health risks of exposure to nanoparticles (NP). In this study, we analysed DNA damage in the leukocytes of 20 workers who were long-term exposed (18 ± 10 years) to NP in their working environment. Blood samples were collected in September 2016, before and after a shift, to assess (i) the chronic effects of NP on DNA (pre-shift samples) and (ii) the acute effects of exposure during the shift (the difference between pre- and post-shift samples).

Medicinal plants used by 'root doctors', local traditional healers in Bié province, Angola.

Ethnopharmacological Relevance: This study is one of the first post-civil war efforts to document traditional botanical knowledge in Bié province, central Angola, in a first step to bring more studies on the use of medicinal plant resources in this area so as to bring new insights into Angolan bio-cultural diversity.

Aim Of The Study: Examine the variety of plant species used for medical purposes, as well as characterize their social and cultural values. Also, it is aimed to compare their uses in the studied region with those in Sub-Saharan Africa and report new ethnomedicinal uses.

Enzymatic Preparation of 2'-5',3'-5'-Cyclic Dinucleotides, Their Binding Properties to Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations.

Cyclic dinucleotides are second messengers in the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which plays an important role in recognizing tumor cells and viral or bacterial infections. They bind to the STING adaptor protein and trigger expression of cytokines via TANK binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) and inhibitor of nuclear factor-κB (IκB) kinase (IKK)/nuclear factor-κB (NFκB) signaling cascades. In this work, we describe an enzymatic preparation of 2'-5',3'-5'-cyclic dinucleotides (2'3'CDNs) with use of cyclic GMP-AMP synthases (cGAS) from human, mouse, and chicken.

The genotoxicity of organic extracts from particulate truck emissions produced at various engine operating modes using diesel or biodiesel (B100) fuel: A pilot study.

An analysis of the toxic effects of emissions should reflect real traffic conditions. The exhaust emissions of particulate matter from diesel engines strongly depend on their operating conditions, with low-speed, low-load "urban creep" conditions, common for truck traffic in heavily congested urban areas, being one of the worst. We aimed to detect the genotoxicity of organic extracts from particulate matter in the exhaust of the diesel engine Zetor 1505 running on diesel and biodiesel (B100) fuels at characteristic modes of extended "urban creep", typical for transit truck traffic in Prague, comparing the first 5 min of idling with extended (20-80 min) idling, full load after idle, "stabilized" full load, and 30% load.

Breathing Out Completely Before Inhalation: The Most Problematic Step in Application Technique in Patients With Non-Mild Chronic Obstructive Pulmonary Disease.

Patient adherence to an inhaled medication application technique (A-ApplT) represents a major health-care issue in patients with chronic obstructive pulmonary disease (COPD). However, there is a lack of studies evaluating this issue thoroughly. The aim of our study was to introduce a universal easy-to-use method of assessing the A-ApplT to chronic medication in moderate to very severe COPD individuals.

A pilot data analysis of a metabolomic HPLC-MS/MS study of patients with COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with multiple clinical faces. Metabolomic profiling studies small molecules present in biological samples by combined use of chromatography with mass spectrometry.

Objectives: The goal of our work was to perform a high performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) metabolomic study to compare the concentrations of metabolites in COPD patients and in controls.

Executive Function Deficits in Seriously Ill Children-Emerging Challenges and Possibilities for Clinical Care.

The past years have seen an incredible increase in the quality and success rates of treatments in pediatric medicine. One of the resulting major challenges refers to the management of primary or secondary residual executive function deficits in affected children. These deficits lead to problems in the ability to acquire, understand, and apply abstract and complex knowledge and to plan, direct, and control actions.