Although graphite is known as one of the most chemically inert materials, we have found that graphene, a single atomic plane of graphite, can react with atomic hydrogen, which transforms this highly ...conductive zero-overlap semimetal into an insulator. Transmission electron microscopy reveals that the obtained graphene derivative (graphane) is crystalline and retains the hexagonal lattice, but its period becomes markedly shorter than that of graphene. The reaction with hydrogen is reversible, so that the original metallic state, the lattice spacing, and even the quantum Hall effect can be restored by annealing. Our work illustrates the concept of graphene as a robust atomic-scale scaffold on the basis of which new two-dimensional crystals with designed electronic and other properties can be created by attaching other atoms and molecules.
Summary
Ichthyosis vulgaris is caused by loss‐of‐function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar ...hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker‐skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin‐deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.
What’s already known about this topic?
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Ichthyosis vulgaris is a common disorder characterized clinically by xerosis, excess scaling, hyperkeratosis, keratosis pilaris, and palmar and plantar hyperlinearity, as well as a strong association with atopic disorders.
What does this study add?
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This review updates the reader on the broader perspective of ichthyosis vulgaris based on recent findings and suggests that clinicians, when appropriate, should warn individuals with ichthyosis vulgaris against environmental exposures, for example nickel, irritants, cats in the household and smoking, as these may cause secondary disease.
Background
While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing‐associated chronic disorders (e.g., cardiovascular ...disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age‐associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels.
Objective
We performed a pilot study to determine whether improving epidermal function reduces circulating pro‐inflammatory cytokine levels in aged humans.
Methods
Thirty‐three aged humans were topically treated twice‐daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age‐related, plasma cytokines (IL‐1β, IL‐6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system.
Results
We also found significantly higher baseline levels of IL‐1β, IL‐6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL‐1β and IL‐6 normalized, while TNFα levels declined substantially.
Conclusion
The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro‐inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.
Background
Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are ...abundant in inflamed skin and thus may contribute to disease pathogenesis.
Methods
Human primary keratinocytes were cultured under differentiation‐promoting conditions in the presence and absence of histamine, histamine receptor agonists and antagonists. The expression of differentiation‐associated genes and epidermal junction proteins was quantified by real‐time PCR, Western blot, and immunofluorescence labeling. The barrier function of human skin models was tested by the application of biotin as tracer molecule.
Results
The addition of histamine to human keratinocyte cultures and organotypic skin models reduced the expression of the differentiation‐associated proteins keratin 1/10, filaggrin, and loricrin by 80–95%. Moreover, the addition of histamine to skin models resulted in the loss of the granular layer and thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R agonist, 2‐pyridylethylamine, suppressed keratinocyte differentiation to the same extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R, virtually abrogated the effect of histamine. The expression of tight junction proteins zona occludens‐1, occludin, claudin‐1, and claudin‐4, as well as that of desmosomal junction proteins corneodesmosin and desmoglein‐1, was down‐regulated by histamine. The tracer molecule biotin readily penetrated the tight junction barrier of skin cultures grown in the presence of histamine, while their diffusion was completely blocked in nontreated controls.
Conclusions
Our findings suggest a new mechanism by which mast cell activation and histamine release contribute to skin barrier defects in inflammatory skin diseases.
ABSTRACT We present the results of optical, near-infrared, and mid-infrared observations of M101 OT2015-1 (PSN J14021678+5426205), a luminous red transient in the Pinwheel galaxy (M101), spanning a ...total of 16 years. The light curve showed two distinct peaks with absolute magnitudes and , on 2014 November 11 and 2015 February 17, respectively. The spectral energy distributions during the second maximum show a cool outburst temperature of K and low expansion velocities ( km s−1) for the H i, Ca ii, Ba ii, and K i lines. From archival data spanning 15-8 years before the outburst, we find a single source consistent with the optically discovered transient, which we attribute to being the progenitor; it has properties consistent with being an F-type yellow supergiant with L ∼ 8.7 L , K, and an estimated mass of M . This star has likely just finished the H-burning phase in the core, started expanding, and is now crossing the Hertzsprung gap. Based on the combination of observed properties, we argue that the progenitor is a binary system, with the more evolved system overfilling the Roche lobe. Comparison with binary evolution models suggests that the outburst was an extremely rare phenomenon, likely associated with the ejection of the common envelope of a massive star. The initial mass of the primary fills the gap between the merger candidates V838 Mon (5−10 M ) and NGC 4490-OT (30 M ).
Abstract
The 2018 summit and flank eruption of Kīlauea Volcano was one of the largest volcanic events in Hawaiʻi in 200 years. Data suggest that a backup in the magma plumbing system at the ...long-lived Puʻu ʻŌʻō eruption site caused widespread pressurization in the volcano, driving magma into the lower flank. The eruption evolved, and its impact expanded, as a sequence of cascading events, allowing relatively minor changes at Puʻu ʻŌʻō to cause major destruction and historic changes across the volcano. Eruption forecasting is inherently challenging in cascading scenarios where magmatic systems may prime gradually and trigger on small events.
Summary Most women of reproductive age have some physical discomfort or dysphoria in the weeks before menstruation. Symptoms are often mild, but can be severe enough to substantially affect daily ...activities. About 5–8% of women thus suffer from severe premenstrual syndrome (PMS); most of these women also meet criteria for premenstrual dysphoric disorder (PMDD). Mood and behavioural symptoms, including irritability, tension, depressed mood, tearfulness, and mood swings, are the most distressing, but somatic complaints, such as breast tenderness and bloating, can also be problematic. We outline theories for the underlying causes of severe PMS, and describe two main methods of treating it: one targeting the hypothalamus-pituitary-ovary axis, and the other targeting brain serotonergic synapses. Fluctuations in gonadal hormone levels trigger the symptoms, and thus interventions that abolish ovarian cyclicity, including long-acting analogues of gonadotropin-releasing hormone (GnRH) or oestradiol (administered as patches or implants), effectively reduce the symptoms, as can some oral contraceptives. The effectiveness of serotonin reuptake inhibitors, taken throughout the cycle or during luteal phases only, is also well established.
The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most ...aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer. In the present study we aim to provide proof for the concept that imatinib can reduce the aggressive phenotype of primary CMS4 colon cancer.
Tumour biopsies from patients with newly diagnosed stage I-III colon cancer will be analysed with a novel RT-qPCR test to pre-select patients with CMS4 tumours. Selected patients (n = 27) will receive treatment with imatinib (400 mg per day) starting two weeks prior to planned tumour resection. To assess treatment-induced changes in the aggressive CMS4 phenotype, RNA sequencing will be performed on pre- and post-treatment tissue samples.
The development of effective adjuvant therapy for primary colon cancer is hindered by multiple factors. First, new drugs that may have value in the prevention of (early) distant recurrence are almost always first tested in patients with heavily pre-treated metastatic disease. Second, measuring on-target drug effects and biological consequences in tumour tissue is not commonly a part of the study design. Third, due to the lack of patient selection tools, clinical trials in the adjuvant setting require large patient populations. Finally, the evaluation of recurrence-prevention requires a long-term follow-up. In the ImPACCT trial these issues are addressed by including newly diagnosed pre-selected patients with CMS4 tumours prior to primary tumour resection, rather than non-selected patients with late-stage disease. By making use of the pre-operative window period, the biological effect of imatinib treatment on CMS4 tumours can be rapidly assessed. Delivering proof-of-concept for drug action in early stage disease should form the basis for the design of future trials with subtype-targeted therapies in colon cancer patients.
ClinicalTrials.gov: NCT02685046 . Registration date: February 9, 2016.
The Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) trial did not show a significant benefit of percutaneous coronary intervention (PCI) of the concurrent ...chronic total occlusion (CTO) in ST-segment elevation myocardial infarction (STEMI) patients on global left ventricular (LV) systolic function. However a possible treatment effect will be most pronounced in the CTO territory. Therefore, we aimed to study the effect of CTO PCI compared to no-CTO PCI on the recovery of regional LV function, particularly in the CTO territory.
Using cardiovascular magnetic resonance (CMR) we studied 180 of the 302 EXPLORE patients with serial CMR (baseline and 4 months follow-up). Segmental wall thickening (SWT) was quantified on cine images by an independent core laboratory. Dysfunctional segments were defined as SWT < 45%. Dysfunctional segments were further analyzed by viability (transmural extent of infarction (TEI) ≤50%.). All outcomes were stratified for randomization treatment.
In the dysfunctional segments in the CTO territory recovery of SWT was better after CTO PCI compared to no-CTO PCI (ΔSWT 17 ± 27% vs 11 ± 23%, p = 0.03). This recovery was most pronounced in the dysfunctional but viable segments(TEI < 50%) (ΔSWT 17 ± 27% vs 11 ± 22%, p = 0.02). Furthermore in the CTO territory, recovery of SWT was significantly better in the dysfunctional segments in patients with Rentrop grade 2-3 collaterals compared to grade 0-1 collaterals to the CTO (16 ± 26% versus 11 ± 24%, p = 0.04).
CTO PCI compared with no-CTO PCI is associated with a greater recovery of regional systolic function in the CTO territory, especially in the dysfunctional but viable segments. Further research is needed to evaluate the use of CMR in selecting post-STEMI patients for CTO PCI and the effect of regional LV function recovery on clinical outcome.
Trialregister.nl NTR1108 , Date registered NTR: 30-okt-2007.
ABSTRACT
Objective
To establish reference curves for size and volume of the fetal kidney, renal pelvis and adrenal gland, as measured using ultrasound from the 15th week of gestation.
Methods
This ...was a prospective, longitudinal study of 96 fetuses in low‐risk singleton pregnancies, in which we performed serial ultrasound examinations at 4‐week intervals. The length and anteroposterior and transverse diameters of both kidneys, the anteroposterior and transverse diameters of the renal pelvises and the length of the adrenal glands were measured three times at each examination, with the average being used for further analysis. Reference charts were constructed using multilevel statistical analysis and comparisons were made with previously published charts derived from cross‐sectional data.
Results
We present nomograms for fetal kidney dimensions and volume, renal pelvis dimensions and adrenal gland length. The new charts show differences in shape and have narrower percentile bands in comparison to previously published reference ranges.
Conclusions
These new charts of measurements of the fetal kidney, renal pelvis and adrenal gland, from a prospective, longitudinal study, may be useful in the diagnosis and assessment of pathology of the kidney and adrenal gland.
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