Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis.

We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, complete remission (CR) and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal hematopoiesis of indeterminate potential years before AML, older age, secondary AML and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2).

Trait- and pre-sleep-state-dependent arousal in insomnia disorders: what role may sleep reactivity and sleep-related metacognitions play? A pilot study.

Objective: Research into the cause of chronic insomnia has identified hyperarousal as a key factor, which is likely to have both trait and state components. Sleep-related cognition, metacognition, and sleep reactivity also play an important role in insomnia. Our aim was to investigate how these insomnia-related constructs are associated with trait predisposition and pre-sleep arousal in subjects with an insomnia disorder.

Aging Changes of the Male Lips-A Lesser Evil Than in Females?

Background: Although aging changes of the female perioral region and aesthetic procedures for perioral rejuvenation are described in literature, specific data for the male population are lacking. This study aims to evaluate perioral aging process in the male population to compare quality and quantity of the observed changes to the female population.

Methods: Magnetic resonance imaging (MRI) scans of 22 male subjects, were recruited into 2 age groups: young (20-35 years) and old (65-80 years) and the following parameters were measured: length of visible upper lip, thickness of upper lip at the level of vermilion border, thickness of upper lip at the level of the mid lip, and cross-section area of upper lip.

German translation and content validation of the OSTRC Questionnaire on overuse injuries and health problems.

Objective: The aim of this study was to translate, culturally adapt and validate the Oslo Sports Trauma Research Centre (OSTRC) Questionnaire on Health Problems into the German context.

Methods: A slightly modified back-translation method was used to translate the questionnaire. Validation was done in 24 high-level Paralympic athletes followed over 20 consecutive weeks.

Metabolic Response to XD14 Treatment in Human Breast Cancer Cell Line MCF-7.

XD14 is a 4-acyl pyrrole derivative, which was discovered by a high-throughput virtual screening experiment. XD14 inhibits bromodomain and extra-terminal domain (BET) proteins (BRD2, BRD3, BRD4 and BRDT) and consequently suppresses cell proliferation. In this study, metabolic profiling reveals the molecular effects in the human breast cancer cell line MCF-7 (Michigan Cancer Foundation-7) treated by XD14.

Identification and Structure-Activity Relationship Studies of Small-Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1.

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small-molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure- and ligand-based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds.

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Background: Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown.

Methods: We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.

Independence and health related quality of life in 200 onco-geriatric surgical patients within 6 months of follow-up: Who is at risk to lose?

Aims: Comprehensive Geriatric Assessment (CGA) provides information on aspects of older patients to predict risks and benefits of interventions.

Methods: To evaluate the application of CGA (including quality of life (QOL)) for the risk prediction of postoperative dependence and QOL in elderly patients with malignant tumours, a prospective observational study including 200 patients >70 years was performed. The primary outcome was postoperative activities of daily living (ADL < 95), secondary outcome was QOL at 6 months.

Cartilage-Repair Innovation at a Standstill: Methodologic and Regulatory Pathways to Breaking Free.

Articular cartilage defects strongly predispose patients to developing early joint degeneration and osteoarthritis, but for more than 15 years, no new cartilage-repair technologies that we know of have been approved by the U.S. Food and Drug Administration.

Identification of Highly Potent Protein Kinase C-Related Kinase 1 Inhibitors by Virtual Screening, Binding Free Energy Rescoring, and in vitro Testing.

Despite the considerable interest in protein kinase C-related kinase 1 (PRK1) as a target in cancer research, there is still a lack of PRK1 inhibitors with suitable selectivity profiles and physicochemical properties. To identify new PRK1 inhibitors we applied a virtual screening approach, which combines ensemble docking, minimization of the protein-ligand complex, binding free energy calculations, and application of quantitative structure-activity relationship (QSAR) models for predicting in vitro activity. The developed approach was then applied in a prospective manner to screen available libraries of kinase inhibitors from Selleck and GlaxoSmithKline (GSK).

A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients.

Background: Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI.

Patients And Methods: A multicenter randomized, controlled trial was conducted at 10 German hematology departments.

Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group.

A self-made, low-cost infrared system for evaluating the sciatic functional index in mice.

The sciatic functional index (SFI) is a popular parameter for peripheral nerve evaluation that relies on footprints obtained with ink and paper. Drawbacks include smearing artefacts and a lack of dynamic information during measurement. Modern applications use digitized systems that can deliver results with less analytical effort and fewer mice.

Time-dependent changes in mortality and transformation risk in MDS.

In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database.

A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.

CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia.

Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy.

The term epigenetics is defined as heritable changes in gene expression that are not due to alterations of the DNA sequence. In the last years, it has become more and more evident that dysregulated epigenetic regulatory processes have a central role in cancer onset and progression. In contrast to DNA mutations, epigenetic modifications are reversible and, hence, suitable for pharmacological interventions.

Association between stress-related sleep reactivity and cognitive processes in insomnia disorder and insomnia subgroups: preliminary results.

Objective: Stress-related sleep reactivity, sleep-related cognitions, and psychological factors play an important role in insomnia. The aim was to investigate their possible association in Insomnia Disorder, insomnia subgroups, and healthy subjects.

Methods: The cross-sectional study consisted of 93 subjects who met diagnostic criteria for Insomnia Disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and of 30 healthy subjects.

Lower Health-Related Quality of Life in Polytrauma Patients: Long-Term Follow-Up After Over 5 Years.

Although trauma-associated mortality has fallen in recent decades, and medical care has continued to improve in many fields, the quality of life after experiencing polytrauma has attracted little attention in the literature. This group of patients suffer from persisting physical disabilities. Moreover, they experience long-term social, emotional, and psychological effects that limit/lower considerably their quality of life.

Nasturtium (Indian cress, Tropaeolum majus nanum) dually blocks the COX and LOX pathway in primary human immune cells.

Background: Nasturtium (Indian cress, Tropaeolum majus) is known for its pharmacological value in the treatment of bacterial infections of the upper air tract and urinary bladder. However, scientific data on the anti-inflammatory potency in human-derived cells is missing.

Purpose: The aim of this study was to investigate the potential of nasturtium to inhibit the lipopolysaccharide (LPS) induced inflammatory response in primary human cells of the immune system.

Data-driven analysis of simultaneous EEG/fMRI reveals neurophysiological phenotypes of impulse control.

Response inhibition is the ability to suppress inadequate but prepotent or ongoing response tendencies. A fronto-striatal network is involved in these processes. Between-subject differences in the intra-individual variability have been suggested to constitute a key to pathological processes underlying impulse control disorders.

Microsurgical reconstruction of oncological scalp defects in the elderly.

The incidence of scalp tumors requiring radical excision increases with age. Free flap surgery is the standard reconstructive option for large defects; however, there is an ongoing uncertainty about its safety in the elderly. We conducted a review of data and report on 19 patients aged ≥75 years and 13 < 75 years.

Application of Transcranial Direct Current Stimulation in Neurorehabilitation: The Modulatory Effect of Sleep.

The relationship between sleep disorders and neurological disorders is often reciprocal, such that sleep disorders are worsened by neurological symptoms and that neurological disorders are aggravated by poor sleep. Animal and human studies further suggest that sleep disruption not only worsens single neurological symptoms but may also lead to long-term negative outcomes. This suggests that sleep may play a fundamental role in neurorehabilitation and recovery.