The decylTPP mitochondria-targeting moiety lowers electron transport chain supercomplex levels in primary human skin fibroblasts.

Attachment of cargo molecules to lipophilic triphenylphosphonium (TPP) cations is a widely applied strategy for mitochondrial targeting. We previously demonstrated that the vitamin E-derived antioxidant Trolox increases the levels of active mitochondrial complex I (CI), the first complex of the electron transport chain (ETC), in primary human skin fibroblasts (PHSFs) of Leigh Syndrome (LS) patients with isolated CI deficiency. Primed by this finding, we here studied the cellular effects of mitochondria-targeted Trolox (MitoE10), mitochondria-targeted ubiquinone (MitoQ10) and their mitochondria-targeting moiety decylTPP (C-TPP).

The Effect of Lifestyle Changes on Disease Severity and Quality of Life in Patients with Plaque Psoriasis: A Narrative Review.

Objective: To evaluate the effect of lifestyle changes on the severity of psoriasis and the quality of life in patients with psoriasis.

Methods: For this narrative review, PubMed, Embase and ClinicalTrials.gov were searched for lifestyle intervention studies with an intervention duration of at least 12 weeks.

Cardiovascular outcome 6 months after severe coronavirus disease 2019 infection.

Objectives: In coronavirus disease 2019 (COVID-19), cardiovascular risk factors and myocardial injury relate to increased mortality. We evaluated the extent of cardiac sequelae 6 months after hospital discharge in patients surviving ICU hospitalization for COVID-19.

Methods: All survivors of Maastricht-ICU were invited for comprehensive cardiovascular evaluation 6 months after discharge from ICU.

Local inhibition of TGF-β1 signaling improves Th17/Treg balance but not joint pathology during experimental arthritis.

TGF-β1 is an important growth factor to promote the differentiation of T helper 17 (Th17) and regulatory T cells (Treg). The potential of TGF-β1 as therapeutic target in T cell-mediated diseases like rheumatoid arthritis (RA) is unclear. We investigated the effect of TGF-β1 inhibition on murine Th17 differentiation in vitro, on human RA synovial explants ex vivo, and on the development of experimental arthritis in vivo.

Transferrin Saturation/Hepcidin Ratio Discriminates -Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia.

Pathogenic variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes.

CRISPR-Cas9‒Based Genomic Engineering in Keratinocytes: From Technology to Application.

CRISPR-Cas9 is the most straightforward genome-editing tool to date. However, its implementation across disciplines is hampered by variable genome-editing efficiencies, reduced cell viability, and low success rates in obtaining clonal cell lines. This review aims to recognize all CRISPR-Cas9‒related work within the experimental dermatology field to identify key factors for successful strategies in the different keratinocyte (KC) cell sources available.

Identification of Keratinocyte Mitogens: Implications for Hyperproliferation in Psoriasis and Atopic Dermatitis.

Psoriasis and atopic dermatitis are chronic inflammatory skin diseases characterized by keratinocyte (KC) hyperproliferation and epidermal acanthosis (hyperplasia). The milieu of disease-associated cytokines and soluble factors is considered a mitogenic factor; however, pinpointing the exact mitogens in this complex microenvironment is challenging. We employed organotypic human epidermal equivalents, faithfully mimicking native epidermal proliferation and stratification, to evaluate the proliferative effects of a broad panel of (literature-based) potential mitogens.

Flower Bulb Waste Material is a Natural Niche for the Sexual Cycle in .

With population genetic evidence of recombination ongoing in the natural population and a sexual cycle demonstrated in the laboratory the question remained what the natural niche for sex is. Composting plant-waste material is a known substrate of to thrive and withstand temperatures even up to 70°C. Previous studies have shown indirect evidence for sexual reproduction in these heaps but never directly demonstrated the sexual structures due to technical limitations.

Colonic expression of calcium transporter TRPV6 is regulated by dietary sodium butyrate.

Dietary fibers have been shown to increase the intestinal absorption of calcium (Ca) and magnesium (Mg). However, the mechanisms that explain the enhanced electrolyte absorption remain unknown. Therefore, this study aims to investigate the short-term and long-term effects of 5% (w/w) sodium butyrate (Na-butyrate), an important end-metabolite of bacterial fermentation of dietary fibers, on Ca and Mg homeostasis in mice.

Does initial buccal crest thickness affect final buccal crest thickness after flapless immediate implant placement and provisionalization: A prospective cone beam computed tomogram cohort study.

Background: Flapless immediate implant placement and provisionalization (FIIPP) in the aesthetic zone is still controversial. Especially, an initial buccal crest thickness (BCT) of ≤1 mm is thought to be disruptive for the final buccal crest stability jeopardizing the aesthetic outcome.

Purpose: To radiographically assess the BCT and buccal crest height (BCH) after 1 year and to calculate the correlation between initial and final achieved BCT.

When You Do Not Get the Whole Picture: Scene Perception After Occipital Cortex Lesions.

Occipital cortex lesions (OCLs) typically result in visual field defects (VFDs) contralateral to the damage. VFDs are usually mapped with perimetry involving the detection of point targets. This, however, ignores the important role of integration of visual information across locations in many tasks of everyday life.

Maternal pre-pregnancy overweight and neonatal gut bacterial colonization are associated with cognitive development and gut microbiota composition in pre-school-age offspring.

Maternal gestational obesity is a risk factor for offspring's neurodevelopment and later neuro-cognitive disorders. Altered gut microbiota composition has been found in patients with neurocognitive disorders, and in relation to maternal metabolic health. We explored the associations between gut microbiota and cognitive development during infancy, and their link with maternal obesity.

The Role of De Novo Variants in Formation of Human Anorectal Malformations.

Anorectal malformations (ARM) represent a rare birth defect of the hindgut that occur in approximately 1 in 3000 live births. Around 60% of ARM occur with associated anomalies including defined genetic syndromes and associations with chromosomal aberrations. The etiology of ARM is heterogeneous, with the individual environmental or genetic risk factors remaining unknown for the majority of cases.

Attitudes and behaviour regarding dose reduction of biologics for psoriasis: a survey among dermatologists worldwide.

Dose reduction (DR) of biologics, where possible, seems promising for more efficient use of expensive biologics. For implementation of DR strategies, it is essential to get insight in factors that influence implementation. The objective of this study was to evaluate the attitudes and behaviour regarding dose reduction of biologic therapies for psoriasis among psoriasis expert dermatologists worldwide.

Flood Control: How Milk-Derived Extracellular Vesicles Can Help to Improve the Intestinal Barrier Function and Break the Gut-Joint Axis in Rheumatoid Arthritis.

Unlabelled: Many studies provided compelling evidence that extracellular vesicles (EVs) are involved in the regulation of the immune response, acting as both enhancers and dampeners of the immune system, depending on the source and type of vesicle. Research, including ours, has shown anti-inflammatory effects of milk-derived EVs, using human breast milk as well as bovine colostrum and store-bought pasteurized cow milk, in systems as well as therapeutically in animal models. Although it is not completely elucidated which proteins and miRNAs within the milk-derived EVs contribute to these immunosuppressive capacities, one proposed mechanism of action of the EVs is the modulation of the crosstalk between the (intestinal) microbiome and their host health.

Permanent pacemaker implantation following transcatheter aortic valve implantation using self-expandable, balloon-expandable, or mechanically expandable devices: a network meta-analysis.

Aims: Permanent pacemaker implantation (PPI) still limits the expansion of indications for transcatheter aortic valve implantation (TAVI). Comparison between different systems remains scarce. We aimed to determine the impact of the device type used on post-TAVI PPI.

Incidence and predictors of permanent pacemaker implantation after surgical aortic v alve replacement: Data of the Netherlands Heart Registration (NHR).

Objective: Permanent pacemaker implantation (PPI) after surgical aortic valve replacement (SAVR) remains a frequent complication. Predictors, however, have been mainly investigated in single-center studies. Therefore, nationwide data were used to identify patients-and procedural risk factors for postoperative PPI.

Impact of Bundle Branch Block on Permanent Pacemaker Implantation after Transcatheter Aortic Valve Implantation: A Meta-Analysis.

Data regarding the impact of infra-Hisian conduction disturbances leading to permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) remain limited. The aim of this study was to determine the impact of right and/or left bundle branch block (RBBB/LBBB) on post-TAVI PPI. We performed a systematic literature review to identify studies reporting on RBBB and/or LBBB status and post-TAVI PPI.

Optimized bacterial DNA isolation method for microbiome analysis of human tissues.

Recent advances in microbiome sequencing have rendered new insights into the role of the microbiome in human health with potential clinical implications. Unfortunately, the presence of host DNA in tissue isolates has hampered the analysis of host-associated bacteria. Here, we present a DNA isolation protocol for tissue, optimized on biopsies from resected human colons (~2-5 mm in size), which includes reduction of human DNA without distortion of relative bacterial abundance at the phylum level.

KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum.

Variants in KCNT1, encoding a sodium-gated potassium channel (subfamily T member 1), have been associated with a spectrum of epilepsies and neurodevelopmental disorders. These range from familial autosomal dominant or sporadic sleep-related hypermotor epilepsy to epilepsy of infancy with migrating focal seizures (EIMFS) and include developmental and epileptic encephalopathies. This study aims to provide a comprehensive overview of the phenotypic and genotypic spectrum of KCNT1 mutation-related epileptic disorders in 248 individuals, including 66 previously unpublished and 182 published cases, the largest cohort reported so far.

Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care.

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect.

G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis.

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35.

EHRA expert consensus statement and practical guide on optimal implantation technique for conventional pacemakers and implantable cardioverter-defibrillators: endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin-American Heart Rhythm Society (LAHRS).

With the global increase in device implantations, there is a growing need to train physicians to implant pacemakers and implantable cardioverter-defibrillators. Although there are international recommendations for device indications and programming, there is no consensus to date regarding implantation technique. This document is founded on a systematic literature search and review, and on consensus from an international task force.

The bidirectional interaction between atrial fibrillation and heart failure: consequences for the management of both diseases.

Atrial fibrillation (AF) and heart failure (HF) are both highly prevalent diseases and are accompanied by a significant disease burden and increased mortality. Although the conditions may exist independently, they often go hand in hand as each is able to provoke, sustain, and aggravate the other. In addition, the diseases share a risk profile with several coinciding cardiovascular risk factors, promoting the odds of developing both AF and HF separately from each other.

Do Women Require Less Permanent Pacemaker After Transcatheter Aortic Valve Implantation? A Meta-Analysis and Meta-Regression.

Background Limited clinical evidence and literature are available about the potential impact of sex on permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI). The aim of this work was to evaluate the relationship between sexes and atrioventricular conduction disturbances requiring PPI after TAVI. Methods and Results Data were obtained from 46 studies from PubMed reporting information about the impact of patient sex on PPI after TAVI.