Drug Development.

Background: ALZ-801 (valiltramiprosate), an oral brain-penetrant amyloid-oligomer inhibitor in Phase 3 testing in APOE4/4 homozygotes (APOLLOE4 trial). A 2-year Phase 2 biomarker study was completed evaluating ALZ-801 (265 mg BID) on plasma biomarkers, MRI, cognition, and clinical benefit in EAD APOE4 carriers. At trial end, subjects could enroll in a 1-year long-term extension with an ongoing biomarker and cognition analysis.

Prevalence of Borrelia burgdorferi sensu lato infection in the Czech Republic.

Introduction: Lyme borreliosis (LB), an infection caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. To further characterize the LB burden in the Czech Republic, we conducted a seroprevalence study and estimated the incidence of symptomatic Bbsl infections.

Methods: Anti-Bbsl IgM and IgG antibodies were detected in sera collected from the adult population in 2011 -2012 by enzyme-linked immunosorbent assay and immunoblot tests at the National Reference Laboratory.

Characterization of Hemoglobin Variants by Capillary Electrophoresis, UV-Vis, and FTIR Spectroscopy.

Hemoglobinopathies, hereditary disorders affecting the structure or production of hemoglobin, were detected by routine HbA measurements by capillary electrophoresis (CE) at the University Hospital Motol, Prague. The potential of ultraviolet-visible (UV-Vis) and Fourier-transform infrared (FTIR) spectroscopy for the detection and characterization of hemoglobinopathies was investigated. FTIR spectra were recorded with a very high resolution (0.

The spatially informed mFISHseq assay resolves biomarker discordance and predicts treatment response in breast cancer.

Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity.

Using therapeutic letters in group schematherapy.

Objective: This article focuses on utilizing therapeutic letters within group schema therapy-an innovative therapeutic approach that integrates elements from various therapeutic disciplines. The primary aim is to explore how therapeutic letters can enhance the therapeutic process and support the treatment of patients.

Methods: To achieve this objective, we conducted a narrative literature review centred on schema therapy and using therapeutic letters as a therapeutic strategy.

The use of imagery in group schema therapy.

This article describes using imagery approaches during group schema therapy (GST). Imagery approaches are an important tool for identifying and changing maladaptive schema modes and early maladaptive schemas. It summarises the theoretical background of the group imagery method and practical case vignettes.

Managing supervisory drift in cognitive behavioral therapy: A narrative review with case vignettes.

Drift is a phenomenon that can occur in cognitive-behavioral supervision, where core components of supervision are omitted, avoided, or deprioritized. This narrative review explores the signs, reasons, and impact of supervisory drift at the experiential, cognitive, and emotional levels for both the supervisor and the supervisee. Additionally, the article presents potential solutions for preventing and addressing supervisory drift, such as staying on track, anticipating problems before they arise, adapting supervision to the supervisee's needs, using active supervision methods to understand drift better, engaging in Supervision of Supervision (SoS), and using alliance measures.

Oxidative DNA Damage and Arterial Hypertension in Light of Current ESC Guidelines.

A new insight into oxidative stress is based on oxidative deoxyribonucleic acid (DNA) damage. DNA is the pivotal biopolymer for life and health. Arterial hypertension (HT) is a globally common disease and a major risk factor for numerous cardiovascular (CV) conditions and non-cardiac complications, making it a significant health and socio-economic problem.

SB16 versus reference denosumab in postmenopausal women with osteoporosis: 18-month outcomes of a phase III randomized clinical trial.

Purpose: This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16.

Methods: 457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck.

Burden of Myasthenia Gravis in the Czech Republic: Analysis of the Nationwide Patient Registry.

Introduction: The main goal of this study was to describe the Czech population of patients with MG in terms of demographics, disease characteristics, management approaches, and treatment trends.

Methods: We selected all patients, both incident and prevalent, who were enrolled in the Czech MyReg registry between August 24, 2015 and November 19, 2021. For the descriptive analysis, all patients enrolled in the registry, regardless of their date of diagnosis or date of enrolment, were included.

Unique and Common Agonists Activate the Insect Juvenile Hormone Receptor and the Human AHR.

Transcription factors of the bHLH-PAS family play vital roles in animal development, physiology, and disease. Two members of the family require binding of low-molecular weight ligands for their activity: the vertebrate aryl hydrocarbon receptor (AHR) and the insect juvenile hormone receptor (JHR). In the fly Drosophila melanogaster, the paralogous proteins GCE and MET constitute the ligand-binding component of JHR complexes.

Practical viewpoints on ethical questions and dilemmas in schema therapy.

Background: Ethics is an inherent part of psychotherapy that protects the interests and rights of all parties engaged in the therapeutic relationship. This article focuses on ethical issues and dilemmas that may arise when using schema therapy.

Method: We created a narrative review by searching the databases PubMed, Web of Science, and Scopus with the keywords "psychotherapy", "schema therapy", "therapeutic relationship", "ethics", "ethical questions", and "ethical dilemmas".

Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis.

Background: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.

Aim: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI).

Efficacy and Safety of Weekly Calcifediol Formulations (75 and 100 µg) in Subjects with Vitamin D Deficiency: A Phase II/III Randomised Trial.

Background/objective: Optimal vitamin D levels are required for bone health and proper functionality of the nervous, musculoskeletal and immune systems. The objective of this study was to assess the efficacy and safety profiles of new weekly calcifediol formulations with the potential to improve adherence and outcome.

Methods: A Phase II-III, double-blind, randomized, multicentre trial (EudraCT 2020-001099-14 and NCT04735926).

Stereochemistry of phosphatidylglycerols from thermotolerant bacteria isolated thermal springs.

Phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-glycerol) (PG) is one of the most abundant lipids in biological membranes. However, the chirality of the carbon atom in glycerol phosphate differs among the three kingdoms: bacteria, archaea, and eukaryotes. It is commonly assumed that archaea, as well as bacteria and eukaryotes, produce only one isomer of PG.

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models.

Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models.

The Influence of Polymer Impregnating Materials on Structural Strengthening of 3D Printed Sand Molds Produced by Binder Jetting Method.

Additive manufacturing offers great potential for various industrial solutions; in particular, the binder jetting method enables the production of components from various materials, including sand molds for casting. This work presents the results of an extensive set of experiments aimed at enhancing the structural strengthening of 3D-printed sand molds. Structural strengthening was achieved by impregnating the sand-printed structures with two polymer materials: epoxy resin and silicone varnish.