PPARs in Clinical Experimental Medicine after 35 Years of Worldwide Scientific Investigations and Medical Experiments.

This year marks the 35th anniversary of Professor Walter Wahli's discovery of the PPARs (Peroxisome Proliferator-Activated Receptors) family of nuclear hormone receptors. To mark the occasion, the editors of the scientific periodical Biomolecules decided to publish a special issue in his honor. This paper summarizes what is known about PPARs and shows how trends have changed and how research on PPARs has evolved.

Epigenetic Findings in Twins with Esophageal Atresia.

Esophageal atresia (EA) is the most common malformation of the upper gastrointestinal tract. The estimated incidence of EA is 1 in 3500 births. EA is more frequently observed in boys and in twins.

The hero of American and Polish nations: a molecular look at Thaddeus Kosciuszko's cause of death suggests a contribution of endocarditis caused by Cutibacterium acnes infection.

The remains of the heart tissue of Thaddeus Kosciuszko have been investigated as the possible cause of disease and death of the hero of Polish and American nations. Three specimens, DNA isolated from scrappings of wax surface, from the surface of a wooden plate, and from the linen cloth that have had contact with the object were subjected to nanosequencing. From the first two, among all reads identified, only one classified as Propionibacterium acnes (synonymous current name Cutibacterium acnes), had a purported clinical significance.

Identification and In Silico Characterization of a Novel Gene Variant in a Child with Mucosal Rectal Prolapse.

Rectal prolapse is influenced by many factors including connective tissue dysfunction. Currently, there is no data about genetic contribution in the etiology of this disorder. In this study, we performed trio whole-exome sequencing in an 11-year-old girl with mucosal rectal prolapse and her parents and sibling.

Clinical Evidence Informing Treatment Guidelines on Repurposed Drugs for Hospitalized Patients During the Early COVID-19 Pandemic: Corticosteroids, Anticoagulants, (Hydroxy)chloroquine.

Introduction: In early 2020, the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, overwhelming hospitals with severely ill patients and posing the urgent need for clinical evidence to guide patient care. First treatment options available were repurposed drugs to fight inflammation, coagulopathy, and viral replication. A vast number of clinical studies were launched globally to test their efficacy and safety.

Assessment of Metastatic Colorectal Cancer Patients' Preferences for Biologic Treatments in Germany Using a Discrete Choice Experiment.

Background: Current treatment regimens for metastatic colorectal cancer (mCRC) include biologics such as epidermal growth factor receptor and vascular endothelial growth factor inhibitors, which have specific side-effect profiles. There is a lack of information on mCRC patient preference in Germany regarding biologics in combination with chemotherapy. This study aims to identify German mCRC patients' preference for these treatments PATIENTS AND METHODS: This was a multicenter cross-sectional discrete choice experiment (DCE).

Management of Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Novel Combination Therapies in Routine Clinical Practice in Germany.

Introduction: Multiple myeloma remains an incurable plasma cell malignancy which, despite improvements in overall survival over the last decade, is characterized by recurrent relapse and is associated with a poor prognosis. This study investigates the use of novel agents in current real-world clinical practice in the management of relapsed and/or refractory multiple myeloma (RRMM) in Germany over different lines of therapy.

Methods: A retrospective chart review was conducted for patients with RRMM treated at multiple centers across Germany between May 2017 and June 2018.

Development of a procedure involving artifact examination to determine the species affiliation of its biological material, as illustrated by an attempt to demystify an alleged Nazi lampshade made from human skin.

Objectives: The main purpose of the study was to identify the species origin of the material from which the incriminating lampshade bought at a flea market had been made.

Methods: The histological and molecular biology methods commonly used in forensic genetics were selected to achieve this goal. The DNA for the research was isolated using a QIAamp DNA Mini Kit (Qiagen) according to the manufacturer's protocol for tissues.

Treatment patterns in adults with immune thrombocytopenia before, during and after use of thrombopoietin receptor agonists: a longitudinal prescription database study from Germany.

Objective: To assess real-world treatment patterns in patients with immune thrombocytopenia (ITP) who received thrombopoietin receptor agonists (TPO-RAs) in Germany.

Methods: This was a longitudinal, retrospective study using anonymized patient-level data (IQVIA healthcare prescription database, covering 82% of German statutory prescriptions). Eligible patients (aged ≥18 years) had received ≥1 TPO-RA prescription (romiplostim/eltrombopag) from July 2016 to June 2019 (treatment duration ≥30 days).

The influence of acute coronary syndrome on levels of clopidogrel active metabolite and platelet inhibition in patients with and without CYP2C19*2(681 G>A), *3(636 G>A) and ABCB1(C3435C> T) gene polymorphisms.

Introduction: Although ticagrelor and prasugrel remain the standard antiplatelet treatments in acute coronary syndrome (ACS), numerous patients still present with indications for clopidogrel use.

Aim: We aimed to assess the levels of clopidogrel active metabolite and to evaluate the effect of the drug on platelet inhibition in patients with ACS as compared with those with stable coronary disease. Patients were assessed for the presence of the most common genetic polymorphisms that reduce the absorption () and activation ( and ) of clopidogrel to exclude the effect of genetic variability on drug concentrations and activity.

Original and generic clopidogrel: A comparison of antiplatelet effects and active metabolite concentrations in patients without polymorphisms in the ABCB1 gene and the allele variants CYPC19*2 and *3.

Background: Ticagrelor and prasugrel are widely used as antiplatelet therapy after coronary angioplasty. However, there is a group of patients with indications for clopidogrel treatment. This population includes patients with chronic or acute coronary syndrome who are treated invasively and have contraindications to the use of novel antiplatelet drugs due to antithrombotic treatment (particularly with non-vitamin K antagonist oral anticoagulants).

Healthcare resource utilization and costs among patients with relapsed and/or refractory multiple myeloma treated with proteasome inhibitors in real-world clinical practice in Germany.

Aims: To assess the real-world healthcare resource utilization (HRU) and costs associated with different proteasome inhibitors (PIs) for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM) in Germany.

Methods: We conducted a retrospective medical chart review of treatment patterns, outcomes, and HRU for patients with RRMM treated with bortezomib, carfilzomib, or ixazomib in second- or third-line (2L or 3L) therapy in Germany. Data were collected between 1 January 2017 and 30 June 2017.

Real-World Evaluation of Health-Related Quality of Life in Patients With Multiple Myeloma From Germany.

Introduction: Real-world health-related quality of life (HRQoL) data in patients with multiple myeloma (MM) are scarce. Here, we report HRQoL by line of therapy in adults with MM in clinical practice in Germany.

Patients And Methods: This descriptive, multicenter, observational study included patients receiving all lines of MM therapy or best supportive care (BSC).

The use of hyaluronic acid hydrogel as a tumour bed marker in breast-conserving therapy.

Purpose: To evaluate usefulness of hyaluronic acid (HA) hydrogel as a tumour bed marker in breast conserving therapy (BCT). To analyze inter- (Inter-OV) and intraobserver (Intra-OV) variability of contouring boost target volume (CTV) in external beam radiotherapy (EBRT).

Materials And Methods: Thirty-two patients in the HA group and 30 patients in the control group with an early stage breast cancer were included in the study.

Patient Characteristics and Outcomes of Relapsed/Refractory Multiple Myeloma in Patients Treated with Proteasome Inhibitors in Germany.

Introduction: Real-world data reflects treatments and outcomes in clinical practice in contrast with controlled clinical trials. This study evaluates real-life multiple myeloma (MM) patients receiving proteasome inhibitor (PI)-based treatments in the second or third therapy line in 2017 in Germany.

Methods: This is a retrospective chart review on adult relapsed/refractory MM patients treated with ≥1 dose of a PI-based regimen in either the second or the third line of therapy.

Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population.

Background: Down syndrome (DS) is the most frequent cause of intellectual disability. In 95% of cases, it is caused by simple trisomy of chromosome 21 resulting from nondisjunction of chromosomes in meiotic division. Currently, the molecular and cellular mechanisms responsible for the phenomenon of nondisjunction are unknown.

Distribution of polymorphisms in the CYP2C19 and ABCB1 genes among patients with acute coronary syndrome in Lower Silesian population.

Background: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel administered to treat patients with acute coronary syndrome (ACS) is still being used. However, despite the proven efficacy of this treatment regimen, thromboembolic complications have been observed in some individuals. The reason for this phenomenon is linked to the so-called increased responsiveness of platelets despite high platelet resistance (HPR).

Health-related quality of life of carfilzomib- and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma, based on German benefit assessment data.

Background: Carfilzomib and daratumumab are licensed in relapsed/refractory multiple myeloma (RRMM), but no head-to-head trials have been conducted.

Methods: We used data from dossiers prepared for the German Federal Joint Committee based on two phase III randomized trials of carfilzomib-based therapies (ASPIRE, ENDEAVOR) and two of daratumumab-based therapies (POLLUX, CASTOR) to conduct a descriptive assessment of health-related quality of life (HRQoL). HRQoL was assessed using the European Organisation for Research and Treatment of Cancer 30-item HRQoL Questionnaire, with hazard ratios calculated for carfilzomib- and daratumumab-based therapy versus comparators for time to HRQoL deterioration of ≥ 10 points.

Preliminary analysis of polymorphism of STR markers in the population of domestic cats (Felis catus) in Lower Silesia.

Aim Of The Study: Genetic tests play a crucial role in the crime investigation process and often provide the strongest evidence for case resolution. Although the majority of genetic analyses in the field of criminalistics focus on the human DNA, genetic identification of animals is becoming an increasingly common procedure. Domestic animals, which live around people, may be silent witnesses and even victims of criminal activity.

Differences in the Expression of TLR-2, NOD2, and NF-κB in Placenta Between Twins.

Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors.

Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders.

Aim: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS).

Methods: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria.

Evaluation of Brain Edema Formation Defined By MRI After LINAC-based Stereotactic Radiosurgery.

Background: Peri-lesional edema is a serious and well-known complication of stereotactic radiosurgery (SRS). Here we evaluated edema risk after SRS and assessed its formation and resolution dynamics.

Patients And Methods: 107 patients underwent SRS for heterogeneous diagnoses: 34 (29%) with arteriovenous malformations, 38 (35%) with meningiomas, 16 (15%) with metastatic tumors, 16 (15%) with acoustic neuromas, 3 with (3%) cavernomas, and 2 (2%) each with anaplastic astrocytomas and anaplastic oligoastrocytomas.

First successful DNA isolation and profiling from bone using an approach that is non-destructive toward bone surface.

Commonly used destructive DNA isolation techniques consist of pulverization which leads to the complete destruction of smaller bones or irreversible damage to larger bones through the cutting of extensive fragments. The procedure is totally unacceptable when handling bones which are valuable for anthropological or religious reasons, as museum exhibits or due to emotional factors. Since the Department's team has already resolved this problem in the case of human teeth (A.

Relevance of indirect comparisons in the German early benefit assessment and in comparison to HTA processes in England, France and Scotland.

Early benefit assessment in Germany under the legislative framework of AMNOG (Arzneimittelmarktneuordnungsgesetz) requires direct comparisons of the new drug with appropriate comparators determined by the Federal Joint Committee (G-BA). In case no head-to-head studies are available for direct comparisons, the submission of indirect comparisons is permitted to assess the additional benefit of the new drug. However, the Institute for Quality and Efficiency in Health Care (IQWiG) states a clear preference for head-to-head trials and defines strict requirements for indirect comparisons to be considered in the benefit assessment.

Cardiac arrest during percutaneous coronary intervention in a patient 'resistant' to clopidogrel - successful 50-minute mechanical chest compression.

We report a case of 72-year-old female patient with end-stage chronic kidney disease, undergoing percutaneous coronary intervention (PCI) that resulted in a cardiac arrest caused by a thrombus mediated flow limitation in the left coronary artery. With mechanical cardiopulmonary resuscitation (CPR) PCI of the left main artery was performed successfully during 50 min cardiac arrest. The patient was discharged from the hospital without compromising cardiac function and neurological deficits.