Outcome of transcatheter edge-to-edge mitral valve repair in patients with diabetes mellitus: Results from a real-world cohort.

Background: There are only limited data on patients with diabetes undergoing transcatheter edge-to-edge repair (TEER) in real-world settings. Previous data indicated patients with diabetes to have a worse prognosis. This study sought to evaluate safety and efficacy of TEER in patients with diabetes in a real-world cohort.

An Appraisal to Address Health Consequences of Vitamin D Deficiency With Food Fortification and Supplements: Time to Act!

A symposium entitled "Vitamin D in Prevention and Therapy" was held on May 4-5, 2022, in Homburg, Germany to discuss important new advances in the field, including identification of new vitamin D signaling pathways, of new biologic effects of vitamin D-compounds (e.g., on the microbiome), and convincing proof of the relevance of vitamin D deficiency for the risk and outcome of many chronic diseases, including cancer, cardio-vascular, auto-immune, metabolic, and infectious diseases.

Cross-talk of Aryl Hydrocarbon Receptor (AHR)- and Vitamin D Receptor (VDR)-signaling in Human Keratinocytes.

Background/aim: Vitamin D receptor (VDR), activated upon binding of 1,25(OH)D, was described as a tumor suppressor in the skin. New biological functions of non-classical vitamin D derivatives were recently identified, that are mediated via binding to alternate receptors, including the aryl hydrocarbon receptor (AHR) and that indicate functional interaction between AHR and VDR signaling in various human tissues. We aimed to gain further insights into the cross-talk of VDR and AHR signaling in skin photo-carcinogenesis.

Stereo- and regiodefined DNA-encoded chemical libraries enable efficient tumour-targeting applications.

The encoding of chemical compounds with amplifiable DNA tags facilitates the discovery of small-molecule ligands for proteins. To investigate the impact of stereo- and regiochemistry on ligand discovery, we synthesized a DNA-encoded library of 670,752 derivatives based on 2-azido-3-iodophenylpropionic acids. The library was selected against multiple proteins and yielded specific ligands.

Crosstalk Between Vitamin D and p53 Signaling in Cancer: An Update.

It has now been convincingly shown that vitamin D and p53 signaling protect against spontaneous or carcinogen-induced malignant transformation of cells. The vitamin D receptor (VDR) and the p53/p63/p73 proteins (the p53 family hereafter) exert their effects as receptors/sensors that turn into transcriptional regulators upon stimulus. While the p53 clan, mostly in the nucleoplasm, responds to a large and still growing number of alterations in cellular homeostasis commonly referred to as stress, the nuclear VDR is transcriptionally activated after binding its naturally occurring biologically active ligand 1,25-dihydroxyvitamin D with high affinity.

Role of Formulation Parameters on Intravitreal Dosing Accuracy Using 1 mL Hypodermic Syringes.

Purpose: Evaluation of product viscosity, density and aeration on the dose delivery and accuracy for intravitreal injections with commonly used commercially available hypodermic 1 mL syringes.

Methods: Six commercially available hypodermic 1 mL syringes with different specifications were used for the study. Syringes were filled with the test solutions with different densities and viscosities.

Determining Maximum Allowable Rubber Stopper Displacement for Container Closure Integrity (CCI).

Sterile pharmaceuticals require they be developed and manufactured using suitable container closure systems to maintain sterility until product opening. Characterizing container closure integrity (CCI) in relation to rubber stopper displacement was controversially discussed during the Annex 1 revision process. An automated inspection system can reject units with displaced rubber stoppers, and the related acceptance criteria for such in-process testing can be established by adequate studies.

Characterization of Polymeric Syringes Used for Intravitreal Injection.

Intravitreal (IVT) injection is currently the state of the art for drug delivery to the back of the eye. Drug Products (DP) intended for IVT injections usually pose challenges such as a very low injection volume (e.g.

Evaluation of Different Quality-Relevant Aspects of Closed System Transfer Devices (CSTDs).

Purpose: Health care professionals can be exposed to hazardous drugs such as cytostatics during preparation of drugs for administration. Closed sytem transfer devices (CSTDs) were introduced to provide protection for healthcare professional against unintended exposure to hazardous drugs. The interest in CSTDs has significantly increased after USP <800> monograph was issued.

Association of Vitamin D Receptor Gene Polymorphisms With Melanoma Risk: A Meta-analysis and Systematic Review.

Background/aim: Increasing evidence indicates a relevance of the vitamin D endocrine system for pathogenesis of malignant melanoma. We performed a systematic review and meta-analysis to update previous reports that investigated the association between vitamin D receptor (VDR) gene polymorphisms and melanoma risk.

Materials And Methods: A comprehensive literature search (PubMed, ISI Web of Science) identified a total of 14 studies that were eligible for inclusion in our meta-analysis.

Tandem Affinity Purification and Nano HPLC-ESI-MS/MS Reveal Binding of Vitamin D Receptor to p53 and other New Interaction Partners in HEK 293T Cells.

While nuclear cofactors that contribute to vitamin D receptor (VDR)-mediated gene transcription, including retinoid X receptors, nuclear co-activators and co-repressors, have been extensively investigated, little is known about cytoplasmic VDR-binding partners and the physiological relevance of their interaction. To gain new insight into this topic, we isolated whole-cell protein extracts of 1,25-dihydroxyvitamin D stimulated and UV-B-irradiated vs. non-irradiated HEK 293T cells transfected with a plasmid called pURB VDR C-Term TAP tag.

Solarium Use and Risk for Malignant Melanoma: Meta-analysis and Evidence-based Medicine Systematic Review.

Background: There is an ongoing debate whether solarium use (indoor tanning/artificial UV) may increase the risk for primary cutaneous malignant melanoma.

Aim: A systematic literature search was conducted using MEDLINE and ISI Web of Science. Included studies were critically assessed regarding their risk of bias, and methodological shortcomings.

The Impact of UV-dose, Body Surface Area Exposed and Other Factors on Cutaneous Vitamin D Synthesis Measured as Serum 25(OH)D Concentration: Systematic Review and Meta-analysis.

Background/aim: To optimize public health campaigns concerning UV exposure, it is important to characterize factors that influence UV-induced cutaneous vitamin D production. This systematic review and meta-analysis investigated the impact of different individual and environmental factors including exposed body surface area (BSA), UVB dose and vitamin D status, on serum 25(OH)D concentration.

Materials And Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses, and Meta-analysis of Observational studies in Epidemiology guidelines, a systematic literature search was conducted (MEDLINE; 01/1960-07/2016) investigating the impact of these factors on vitamin D status after artificial UV exposure as main outcome measure.

Endocrine actions of vitamin D in skin: Relevance for photocarcinogenesis of non-melanoma skin cancer, and beyond.

The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH)D and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)D exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH)D are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR).

Challenge and perspective: the relevance of ultraviolet (UV) radiation and the vitamin D endocrine system (VDES) for psoriasis and other inflammatory skin diseases.

During evolution, the ability of many organisms to synthesize vitamin D photochemically represented, and still represents, a major driving factor for the development of life on earth. In humans because not more than 10-20% of the requirement of vitamin D can be satisfied by the diet (under most living conditions in the US and Europe), the remaining 80-90% need to be photochemically synthesized in the skin through the action of solar or artificial ultraviolet-B (UV-B) radiation. The skin is a key organ of the human body's vitamin D endocrine system (VDES), representing both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites.

Targeting the vitamin D endocrine system (VDES) for the management of inflammatory and malignant skin diseases: An historical view and outlook.

Vitamin D represents one of the major driving factors for the development of life on earth and for human evolution. While up to 10-20 % of the human organism's requirements in vitamin D can be obtained by the diet (under most living conditions in the USA and Europe), approximately 90 % of all needed vitamin D has to be photosynthesized in the skin through the action of the sun (ultraviolet-B (UV-B)). The skin represents a key organ of the human body's vitamin D endocrine system (VDES), being both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites.

Prospective Investigation of 25(OH)D3 Serum Concentration Following UVB Narrow Band Phototherapy in Patients with Psoriasis and Atopic Dermatitis.

Vitamin D deficiency represents a major health issue. It is a worldwide endemic and is associated with a broad variety of severe diseases. The skin is a key tissue for the human body's vitamin D endocrine system.

Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes (SNPs) Involved in Skin Pigmentation Are Associated with 25(OH)D Serum Concentration.

Vitamin D deficiency is common and associated with higher risk for and unfavourable outcome of many diseases. Limited data exist on genetic determinants of serum 25(OH)D concentration. In a cohort of the LURIC study (n=2974, median 25(OH)D concentration 15.

BH3-mimetic drugs prevent tumour onset in an orthotopic mouse model of hepatoblastoma.

Drug resistance and metastasis remain major challenges in the treatment of high-risk hepatoblastoma (HB) and require the development of alternative therapeutic strategies. Modulation of apoptosis in HB cells enhances the sensitivity of these cells towards various drugs and has been discussed to enforce treatment. We investigated the impact of apoptosis sensitisers, BH3-mimetics, on the interaction between the host and HB to reduce tumour growth and dissemination while enhancing immunity.

Photoplanimetric evaluation and impedance measurement of split-thickness skin grafts: a new model for objective wound-healing assessment in clinical trials.

Purpose: The objective assessment of wound healing is a challenging task especially in the context of clinical trials. Because the clinical evaluation of wounds and the wound-healing quality is often influenced by the subjective view of the physician, there is great need for a reliable, quantitative and objective wound model that would help to obtain statistically useful data. Here, we present a wound model and non-invasive analysis techniques to evaluate human wound healing.

In-vitro hemodynamics of stented bioprosthetic heart valves in the tilted implantation position.

Background And Aim Of The Study: Although, in small aortic annulus or aortic annulus calcification, it is recommended that valves are implanted in a tilted position, mechanical valves show impaired hemodynamic performance when positioned in this way. To date, no investigations have been conducted with biological valves implanted in a tilted position.

Methods: Measurements were performed in a pulsatile flow simulator.

[Local therapy of grade IIa burns: efficacy and tolerability of a new hydrosome wound gel for the local treatment of grade IIa burns as compared with silver sulfadiazine ointment].

Background: A new hydrosome wound gel is based on a new mechanism of action. It contains hydrosomes that penetrate to the wound bed and supply the wound with phospholipids, which are identical to membrane phospholipids of human cells. In this manner it supports the proliferative processes during wound healing.