Exploring Problematic Mobile Phone Attachment and Associations to Anxiety and Inhibitory Control After a Short-Term Smartphone Separation

This study investigates problematic smartphone attachment under conditions of short-term smartphone separation. Two experimental studies with randomized group allocation were designed to investigate effects of smartphone separation on anxiety and inhibitory control. Problematic smartphone use pathways were explored using a self-report measure. In the first experiment (N= 85) smartphone addicted participants showed an increase in state anxiety after 20 min of separation from their smartphones compared to a control group of non-addicted participants. There was no evidence for impaired inhibitory control based on a period of smartphone separation. In the second experiment the methodology was slightly varied, and the participants (N= 95) were provided with a task during a smartphone separation of 15 min. This led to a reduction of state anxiety for problematic attached participants but did not result in a change for unproblematic attached participants. Problematic attached participants showed a larger disturbance in inhibitory control undergoing a separation period than unproblematic attached participants. Moreover, the results provide supplementary evidence for the existence of specific problematic smartphone attachment pathways and further variables

A Critical Appraisal of Strategies to Optimize Vitamin D Status in Germany, a Population with a Western Diet

During the last decade, our scientific knowledge of the pleiotropic biological effects of vitamin D metabolites and their relevance to human health has expanded widely. Beyond the well-known key role of vitamin D in calcium homeostasis and bone health, it has been shown that vitamin D deficiency is associated with a broad variety of independent diseases, including several types of cancer, and with increased overall mortality. Moreover, recent findings have demonstrated biological effects of the vitamin D endocrine system that are not mediated via activation of the classical nuclear vitamin D receptor (VDR) by binding with high affinity to its corresponding ligand, the biologically active vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). In contrast, many of these new biological effects of vitamin D compounds, including regulation of the circadian clock and many metabolic functions, are mediated by other vitamin D metabolites, including 20-hydroxyvitamin D and 20,23-dihydroxyvitamin D, and involve their binding to the aryl hydrocarbon receptor (AhR) and retinoid-orphan receptor (ROR). In most populations, including the German population, UVB-induced cutaneous vitamin D production is the main source for fulfilling the human body’s requirements of vitamin D. However, this causes a dilemma because solar or artificial UVR exposure is associated with skin cancer risk. In addition to UVB-induced vitamin D production in skin, in humans, there are two other possible sources of vitamin D: from diet and supplements. However, only a few natural foods contain substantial amounts of vitamin D, and in most populations, the dietary source of vitamin D cannot fulfill the body´s requirements. Because an increasing body of evidence has convincingly demonstrated that vitamin D deficiency is very common worldwide, it is the aim of this paper to (i) give an update of the vitamin D status in a population with a western diet, namely, the German population, and to (ii) develop strategies to optimize the vitamin D supply that consider both the advantages as well as the disadvantages/risks of different approaches, including increasing vitamin D status by dietary intake, by supplements, or by UVB-induced cutaneous synthesis of vitamin D

Live Longer with Vitamin D?

The global burden of vitamin D deficiency or insufficiency is of great concern for public health. According to recent studies, vitamin D deficiency is an important etiological factor in the pathogenesis of many chronic diseases. Whether or not there is a connection between 25-hydoxyvitamin D (25(OH)D) status and overall mortality is a matter of considerable debate. A new meta-analysis confirmed that low 25(OH)D levels were associated with a significant increased risk for all-cause mortality. Individuals with severe vitamin D deficiency have almost twice the mortality rate as those with 25(OH)D level ≥ 30 ng/mL, (≥75 nmol/L). Unlike previous meta-analyses which suggested that serum 25(OH)D > 50 ng/mL was associated with increased mortality, this new analysis found that there was no increased risk even when 25(OH)D levels were ≥70 ng/mL. In general, closer attention should be paid to vitamin D deficiency in medical and pharmaceutical practice than has been the case hitherto. The results of these studies are consistent with the recommendation to improve the general vitamin D status in children and adults by means of a healthy approach to sunlight exposure, consumption of foods containing vitamin D and supplementation with vitamin D preparations

Neue Interaktionen der Notch- und p53/63/73-Signalwege beim Glioblastom: Jagged1 als direktes p73-Zielgen

Neue Forschungsergebnisse unterstreichen die Bedeutung der funktionell teilweise überlappenden Notch- und p53/p63/p73-Signalwege für Pathogenese, Wachstumsverhalten und Therapie des Glioblastoms. Die dafür verantwortlichen molekularen Mechanismen sind jedoch bislang weitestgehend unbekannt. Ziel dieser Arbeit war es einen möglichen cross-talk zwischen dem Notch-Signalweg und der Transkriptionsfaktorfamilie p53/p63/p73 in Glioblastomzellen zu untersuchen. Wir charakterisierten die Expression wichtiger Komponenten des Notch-Signalwegs (Notch-Rezeptoren1-4; Notch-Liganden: Dll1, 3, 4; Jagged1,2) in humanen Glioblastomzelllinien (Tx3868, Tx3095, U373, U118, U87), wobei die Proteinexpression von Notch1 und Jagged1 mit dem p53-Status der Zelle korrelierte. Notch1 wurde ausschließlich, und Jagged1 wesentlich stärker, in Zellen mit mutiertem p53 (U373) exprimiert, verglichen mit Wildtyp-p53-Zellen (U87). In U373 Zellen war p73 stark exprimiert, dagegen war dieses Protein in Zellen mit Wildtyp-p53 (U87) nicht nachweisbar. Behandlung mit ionisierender Strahlung oder Doxorubicin selegierte eine Zellpopulation mit starker Jagged1-Expression und verändertem Wachstumsverhalten. Die siRNA-vermittelte Hemmung der p73-Expression reduzierte in U373 Zellen die Proteinexpression von Jagged1. Mittels Chromatinimmunpräzipitation zeigten wir in U373-Zellen eine direkte Bindung des p73 Proteins an die Promotorregion des Jagged1-Gens. Deren Intensität nahm nach Behandlung mit ionisierender Strahlung deutlich ab. Unsere Ergebnisse in Glioblastomzellen stehen somit im Einklang mit folgenden Hypothesen: (I) Abhängig vom p53-Status werden wichtige Komponenten des Notch-Signalwegs (u.a. Jagged1) differentiell exprimiert. (II) Behandlung mit ionisierender Strahlung oder Doxorubicin stimuliert die Jagged1-Expression, welche mit verändertem Wachstumsverhalten assoziiert ist. (III) In Zellen mit mutiertem p53 wird die Jagged1-Expression durch das p53-verwandte p73 Protein auf Transkriptionsebene induziert. (IV) Die nach Behandlung mit ionisierender Strahlung nur schwach nachweisbare Bindung des p73 Proteins an die Jagged1-Promotorregion spricht für eine Beteiligung anderer Faktoren an der Regulation dieses Gens. Wir konnten Jagged1 als direktes p73-Zielgen identifizieren und neue Interaktionen zwischen Notch- und p53-Signalwegen nachweisen. Die Relevanz dieser Ergebnisse für Pathogenese, Wachstumsverhalten und Therapie von Glioblastomzellen muss in zukünftigen Untersuchungen geklärt werden.In recent years, scientific progress has convincingly demonstrated an important role of notch and p53/p63/p73 that are in part functionally overlapping, for pathogenesis, growth behaviour and therapy of glioblastomas. However, the underlying molecular mechanism are to date unknown. The aim of this work was to examine a possible cross-talk between Notch-signaling and the transcription factor family p53/p63/p73 in glioblastoma cells. We characterised the expression of important components of the Notch-signaling pathway (Notch receptors 1-4; Notch ligands: Dll1,3,4; Jagged1,2) in human glioblastoma cells (Tx3868, Tx3095, U373, U118, U87) in vitro and could show that the protein expression of Notch1 and Jagged1 correlated with the p53 status of the cells. Notch1 was exclusively, and Jagged1 substantially stronger, expressed in cells with mutant p53 (U373), compared to wild type p53 cells (U87). In U373 cells, p73 was strongly expressed, while this protein was not detected in cells with wild type-p53 (U87). Treatment with ionising radiation or doxorubicin resulted in a cell population with increased Jagged1 expression and modulated growth behaviour. The siRNA-induced suppression of p73 expression reduced the protein expression of Jagged1 in U373 cells. Using chromatinimmunoprecipitation (ChIP) we could prove in U373 cells a direct binding of the p73 protein to the promotor region of the Jagged1 gene. The intensity of this binding decreased after treatment with ionising radiation clearly. Our results in glioblastoma cells are in agreement with the following hypotheses: (I) Depending on the p53 status, important components of the Notch-signaling pathway (including Jagged1) are differentially expressed. (II) Treatment with ionising radiation or doxorubicin stimulates the Jagged1 expression, which is associated with changed growth behaviour. (III) In cells with mutant p53, the Jagged1 expression is induced by p53-related p73 protein at the transcription level. (IV) After treatment with ionising radiation, only weak binding of the p73 protein to the Jagged1-promotor region was shown, indicating a participation of other factors in the regulation of this gene. In conclusion, we succeeded in identifying Jagged1as a direct p73-target gene and in proving new interactions between Notch- and p53/p63/p73-signaling pathways. The relevance of these results for pathogenesis and growth behaviour, as well as for the therapy of glioblastoma, must be confirmed in future investigations

Low Vitamin D Status Predicts Poor Clinical Outcome in Advanced Melanoma Treated With Immune Checkpoint or BRAF/MEK Inhibitors: A Prospective Non-Interventional Side-by-Side Analysis

In melanoma and other malignancies, low vitamin D status is associated with increased risk and poor prognosis. However, there are limited data of the impact of 25(OH)D serum concentration (s.c.) on clinical outcome in advanced melanoma. We tested the hypothesis that vitamin D status is predictive of efficacy and safety in patients treated for metastasized melanoma with B-rapidly accelerated fibrosarcoma (BRAF), mitogen-activated protein kinase kinase (MEK), cytotoxic T lymphocyte-associated protein-4 (CTLA-4), and/or programmed cell death protein-1 (PD-1) inhibitors. Severe vitamin D deficiency [defined as 25(OH)D s.c. <10 ng/ml] was associated with markedly reduced overall (OS) and progress-free (PFS) survival, with increased tumor load [TL; measured as s.c. of S100 protein or lactate dehydrogenase (LDH)], and with a trend for higher frequency of adverse events (AEs). An increase in average 25(OH)D s.c. of 1 ng/ml was associated with a 3.9% reduced risk for progressive disease [hazard ratio (HR) = 0.961, p = 0.044], with a reduction of LDH s.c. of 3.86 U/l (p = 0.034, indicating a reduction of TL), and with a trend for reduced frequency of AEs (AE ratio -0.005; p = 0.295). Patients with average 25(OH)D s.c. ≥10 ng/ml and BRAF-mutant melanoma showed a trend for a higher frequency of AEs as compared to individuals with BRAF wild-type melanomas. Our data indicate that vitamin D deficiency is associated with poor clinical outcome in patients treated for metastasized melanoma with BRAF/MEK inhibitors or immunotherapy. Although it needs to be proven in future interventional trials whether optimizing serum 25(OH)D improves clinical outcome in these patients, we recommend that 25(OH)D s.c. should be analyzed and vitamin D deficiency treated in all patients with advanced melanoma

Characteristics of the Skin Microbiome in Selected Dermatological Conditions : A Narrative Review

The skin is the largest and outermost organ of the human body. The microbial diversity of the skin can be influenced by several variable factors such as physiological state, lifestyle, and geographical locations. Recent years have seen increased interest in research aiming at an improved understanding of the relationship between the human microbiota and several diseases. Albeit understudied, interesting correlations between the skin microbiota and several dermatological conditions have been observed. Studies have shown that a decrease or increase in the abundance of certain microbial communities can be implicated in several dermatological pathologies. This narrative review (i) examines the role of the skin microbiota in the maintenance of skin homeostasis and health, (ii) provides examples on how some common skin diseases (acne inversa, candidiasis, psoriasis) are associated with the dysbiosis of microbial communities, and (iii) describes how recent research approaches used in skin microbiome studies may lead to improved, more sensitive diagnostics and individual therapeutics in the foreseeable future