Thrombosis, Translational Medicine, and Biomarker Research: Moving the Needle.

Arterial and venous thromboembolism are leading causes of morbidity and death worldwide. Despite significant advances in the diagnosis, prognostication, and treatment of thrombotic diseases over the past 3 decades, the adoption of findings stemming from translational biomarker research in clinical practice remains limited. Biomarkers provide an opportunity to enhance our understanding of pathophysiological processes and optimize treatment strategies.

Pulmonary hypertension associated with left heart disease.

Left heart disease (LHD) is the most common cause of pulmonary hypertension (PH), which may be classified further as isolated post-capillary (ipcPH) or combined post- and pre-capillary PH (cpcPH). The 7th World Symposium on Pulmonary Hypertension PH-LHD task force reviewed newly reported randomised clinical trials and contemplated novel opportunities for improving outcome. Results from major randomised clinical trials reinforced prior recommendations against the use of pulmonary arterial hypertension therapy in PH-LHD outside of clinical trials, and suggested possible harm.

Termination of pregnancy for fetal malformation: A traumatic event? A qualitative analysis of women's perception.

To investigate women's experience of termination of pregnancy (TOP) for severe fetal malformation.We focus on women's individual perception of psychological counselling on decision making, experiencing the birth process, seeing and holding the baby as well as emotional processing. An explorative study was conducted with 42 women (the age range was between 21 and 45 years [mean 36.

Antineoplastic efficacy profiles of avapritinib and nintedanib in D816V systemic mastocytosis: a preclinical study.

Systemic mastocytosis (SM) is a hematopoietic neoplasm with a complex pathology and a variable clinical course. Clinical symptoms result from organ infiltration by mast cells (MC) and the effects of pro-inflammatory mediators released during MC activation. In SM, growth and survival of MC are triggered by various oncogenic mutant-forms of the tyrosine kinase KIT.

Patient Experience With Vascular Access Management Informs Satisfaction With Overall Hospitalization Experience.

Peripheral intravenous catheter (PIVC) insertion is a common invasive procedure performed during hospitalization. The present study reports results from a survey of 544 patients who have had PIVC insertion during their hospital stay in Singapore and the Philippines during the period between November 2018 and February 2019. The survey assessed the importance of 5 domains of patient-centered care on patient satisfaction with their hospitalization experience, including pain management, infection prevention, health care provider competence with vascular access, physical comfort, and effectiveness of communication during vascular access management.

Neuroinflammation: 2022 update.

Besides important progress in the understanding of the pathological substrate of COVID-19-associated brain disease, major insights into mechanisms of neurodegeneration in human disease have been provided in neuropathological studies published in 2021. Recently developed techniques, which allow the simultaneous detection of a large battery of different molecules within single cells, have proven useful in the analysis of disease mechanisms in experimental and human neuroinflammatory conditions. They have elucidated protective and detrimental effects of activated microglia, which act in a stage and context-dependent manner in the induction and propagation of neurodegeneration.

Asciminib and ponatinib exert synergistic anti-neoplastic effects on CML cells expressing -compound mutations.

Ponatinib is a tyrosine kinase inhibitor (TKI) directed against BCR-ABL1 which is successfully used in patients with + chronic myeloid leukemia (CML). However, compound mutations may develop during therapy in these patients and may lead to drug resistance. Asciminib is a novel drug capable of targeting most BCR-ABL1 mutant-forms, including BCR-ABL1, but remains ineffective against most BCR-ABL1+ compound mutation-bearing sub-clones.

Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension.

Background Women with chronic hypertension face a 5- to 6-fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt-1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension.

Harnessing cyclotides to design and develop novel peptide GPCR ligands.

Cyclotides are plant-derived cyclic, disulfide-rich peptides with a unique cyclic cystine knot topology that confers them with remarkable structural stability and resistance to proteolytic degradation. Recently, cyclotides have emerged as promising scaffold molecules for designing peptide-based therapeutics. Here, we provide examples of how engineering cyclotides using molecular grafting may lead to the development of novel peptide ligands of G protein-coupled receptors (GPCRs), today's most exploited drug targets.

Non-specific lipid-transfer proteins: Allergen structure and function, cross-reactivity, sensitization, and epidemiology.

Background: Discovered and described 40 years ago, non-specific lipid transfer proteins (nsLTP) are present in many plant species and play an important role protecting plants from stressors such as heat or drought. In the last 20 years, sensitization to nsLTP and consequent reactions to plant foods has become an increasing concern.

Aim: The aim of this paper is to review the evidence for the structure and function of nsLTP allergens, and cross-reactivity, sensitization, and epidemiology of nsLTP allergy.

Degradation of BRD4 - a promising treatment approach not only for hematologic but also for solid cancer.

Bromodomain (BRD) and extra-terminal (BET) proteins are epigenetic readers that regulate gene expression and promote cancer evolution. Pharmacological inactivation of BRD4 has recently been introduced as a promising anti-neoplastic approach that targets MYC oncogene expression. However, resistance against BRD4-targeting drugs has been described.

Expert Opinion: Meditation and Cardiovascular Health: What is the Link?

Meditation as a form of body-mind interaction for primary and secondary prevention in cardiovascular disease has been discussed critically in the past. However, data that aimed to link this intervention to a reduction of various aspects of cardiovascular disease, rendering it a potential part of a cost-effective treatment approach in patients at risk, remain scarce and inconclusive. This article aims to provide an overview of currently available evidence in the literature and the potential impact of meditation on cardiovascular health.

Vaginismus and pregnancy: epidemiological profile and management difficulties.

Background: Vaginismus affects up to 1% of the female population and often represents a physical manifestation of an underlying psychological problem. Our objective was to investigate the psychosomatic impact of vaginismus in pregnant women and evaluate the quality of their therapeutic care in Tunisia.

Methods: We included pregnant patients with vaginismus who presented at our obstetric emergency department between October 2016 and March 2017.

[Primary care of refugees and migrants. Lesson learnt from the EUR-HUMAN project].

In 2015, local wars, starvation and misery in some Middle Eastern, Asian and African countries forced millions of people to leave their homelands. Many of these people migrated toward Europe, reaching Hungary as well. The refugee crisis created significant challenges for all national healthcare systems across Europe.

Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease.

Background: miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD).

Methods: The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD).

Long-lasting complete response to imatinib in a patient with systemic mastocytosis exhibiting wild type KIT.

Systemic mastocytosis (SM) is a hematopoietic disorder characterized by abnormal expansion of mast cells (MCs) in visceral organs. The skin is involved in most cases. In adult patients the transforming KIT mutation D816V is usually present and confers resistance against imatinib.

Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling.

Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signaling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood.

Guidelines and diagnostic algorithm for patients with suspected systemic mastocytosis: a proposal of the Austrian competence network (AUCNM).

Systemic mastocytosis (SM) is a hematopoietic neoplasm characterized by pathologic expansion of tissue mast cells in one or more extracutaneous organs. In most children and most adult patients, skin involvement is found. Childhood patients frequently suffer from cutaneous mastocytosis without systemic involvement, whereas most adult patients are diagnosed as suffering from SM.

Treprostinil for pulmonary hypertension.

Treprostinil is a stable, long-acting prostacyclin analogue which can be administered as a continuous subcutaneous infusion using a portable miniature delivery system. Subcutaneous treprostinil has been shown in a large multicenter randomized controlled trial to improve exercise capacity, clinical state, functional class, pulmonary hemodynamics, and quality of life in patients with pulmonary arterial hypertension, an uncommon disease of poor prognosis. Side effects include facial flush, headache, jaw pain, abdominal cramping, and diarrhea, all typical of prostacyclin, and manageable by symptom-directed dose adjustments, and infusion site pain which may make further treatment impossible in 7%-10% of the patients.

Cost-effectiveness of sitagliptin-based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy.

Objective: Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden.

Serum aluminium and cobalt levels after ceramic-on-ceramic and metal-on-metal total hip replacement.

In a randomised study, 28 patients with a mean age of 62.2 years (32 to 81) with osteoarthritis or avascular necrosis of the hip received either a ceramic-on-ceramic or a metal-on-metal total hip replacement. Apart from the liners the acetabular and femoral components were made of Ti-Al-Nb alloy.