Actinic keratoses show variable histological basal growth patterns - a proposed classification adjustment

Background: Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied. Objective: To investigate the extent of atypical keratinocytes throughout the epidermis and variation in basal growth patterns of AK. Methods: AK lesions occurring on the head/face from patients seen in routine practice were assessed histologically. We determined histological grade (AK I-III), basal growth patterns of atypical keratinocytes (crowding, budding, papillary sprouting) and accompanying parameters. Results: Of the 246 lesions included, 28.0% were histologically classified as AK I, 46.7% as AK II, and 25.2% as AK III. 26.4% of the basal growth patterns were classified as crowding (pro I), 49.6% as budding (pro II), 17.9% as papillary sprouting (pro III) and 6.1% without basal directed growth. No significant correlation of the histological AK I-III grading and underlying growth patterns was observed (P= 0.4666). However, adnexal structure involvement (OR= 2.37; 95%CI 1.21-4.65), infiltration (OR= 2.53; 95%CI 1.31-4.90) and increased number of vessels (OR= 2.56; 95%CI 1.42-4.65) were independent positive predictive markers for pro II and pro III basal growth patterns. Conclusions: Basal growth patterns (pro I-III) in AK do not correlate with the established AK I-III histological grading system. Besides the degree of upward extension, varying degrees of downward extension exist. Histological classification should consider both, upwards and downward growth patterns when assessing AK

The effects of bioactive akermanite on physiochemical, drug-delivery, and biological properties of poly(lactide-co-glycolide) beads

Poly(lactide-co-glycolide) (PLGA) beads have been widely studied as a potential drug/protein carrier. The main shortcomings of PLGA beads are that they lack bioactivity and controllable drug-delivery ability, and their acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Akermanite (AK) (Ca(2) MgSi(2) O(7) ) is a novel bioactive ceramic which has shown excellent bioactivity and degradation in vivo. This study aimed to incorporate AK to PLGA beads to improve the physiochemical, drug-delivery, and biological properties of PLGA beads. The microstructure of beads was characterized by SEM. The effect of AK incorporating into PLGA beads on the mechanical strength, apatite-formation ability, the loading and release of BSA, and the proliferation, and differentiation of bone marrow stromal cells (BMSCs) was investigated. The results showed that the incorporation of AK into PLGA beads altered the anisotropic microporous structure into homogenous one and improved their compressive strength and apatite-formation ability in simulated body fluids (SBF). AK neutralized the acidic products from PLGA beads, leading to stable pH value of 7.4 in biological environment. AK led to a sustainable and controllable release of bovine serum albumin (BSA) in PLGA beads. The incorporation of AK into PLGA beads enhanced the proliferation and alkaline phosphatase activity of BMSCs. This study implies that the incorporation of AK into PLGA beads is a promising method to enhance their physiochemical and biological property. AK/PLGA composite beads are a potential bioactive drug-delivery system for bone tissue repair

Formal normal form of Ak slow fast systems

An Ak slow fast system is a particular type of singularly perturbed ODE. The corresponding slow manifold is defined by the critical points of a universal unfolding of an Ak singularity. In this note we propose a formal normal form of Ak slow fast systems

Strongly intersecting integer partitions

We call a sum a1+a2+• • •+ak a partition of n of length k if a1, a2, . . . , ak and n are positive integers such that a1 ≤ a2 ≤ • • • ≤ ak and n = a1 + a2 + • • • + ak. For i = 1, 2, . . . , k, we call ai the ith part of the sum a1 + a2 + • • • + ak. Let Pn,k be the set of all partitions of n of length k. We say that two partitions a1+a2+• • •+ak and b1+b2+• • •+bk strongly intersect if ai = bi for some i. We call a subset A of Pn,k strongly intersecting if every two partitions in A strongly intersect. Let Pn,k(1) be the set of all partitions in Pn,k whose first part is 1. We prove that if 2 ≤ k ≤ n, then Pn,k(1) is a largest strongly intersecting subset of Pn,k, and uniquely so if and only if k ≥ 4 or k = 3 ≤ n ̸∈ {6, 7, 8} or k = 2 ≤ n ≤ 3.peer-reviewe

A proposed scoring system for assessing the severity of actinic keratosis on the head: actinic keratosis area and severity index

Background: Actinic keratosis (AK) severity is currently evaluated by subjective assessment of patients. Objectives: To develop and perform an initial pilot validation of a new easy-to-use quantitative tool for assessing AK severity on the head. Methods: The actinic keratosis area and severity index (AKASI) for the head was developed based on a review of other severity scoring systems in dermatology, in particular the psoriasis area and severity index (PASI). Initial validation was performed by 13 physicians assessing AK severity in 18 AK patients and two controls using a physician global assessment (PGA) and AKASI. To determine an AKASI score, the head was divided into four regions (scalp, forehead, left/right cheek ear, chin and nose). In each region, the percentage of the area affected by AKs was estimated, and the severities of three clinical signs of AK were assessed: distribution, erythema and thickness. Results: There was a strong correlation between AKASI and PGA scores (Pearson correlation coefficient: 0.86). AKASI was able to discriminate between different PGA categories: mean (SD) AKASI increased from 2.88 (1.18) for ‘light’ to 5.33 (1.48) for ‘moderate’, 8.28 (1.89) for ‘severe’, and 8.73 (3.03) for ‘very severe’ PGA classification. The coefficient of variation for AKASI scores was low and relatively constant across all PGA categories. Conclusions: Actinic keratosis area and severity index is proposed as a new quantitative tool for assessing AK severity on the head. It may be useful in the future evaluation of new AK treatments in clinical studies and the management of AK in daily practice

Pathophysiologisch-serologische, bildgebende und klinische Charakteristika der Neuromyelitis Optica

Hintergrund: Neuromyelitis optica-Spektrum-Erkrankungen (NMOSD) stellen eine Gruppe neuroinflammatorischer Erkrankungen dar, die mit dem klinischen Auftreten von Myelitiden und/oder Optikusneuritiden (ON) einhergeht. Aufgrund zahlreicher überlappender klinischer und paraklinischer Eigenschaften beim Nachweis verschiedener Antikörper, vor allem auch in Abgrenzung zur Multiplen Sklerose (MS), besteht weiterhin der Bedarf nach neuen Biomarkern. Methodik: In zwei Studien wurden NMOSD-Patienten mit positivem Nachweis für Aquaporin-4-Antikörper (AQP-4-Ak) mittels 7 Tesla (T) Magnetresonanztomografie (MRT) hinsichtlich der I) periventrikulären Venendichte (PVA) in T2*-gewichteten Aufnahmen und II) der Phasenverschiebung in suszeptibilitätsgewichteten Sequenzen untersucht. Als Vergleich dienten die Ergebnisse von Patienten mit MS und gesunden Kontrollen (HC). In einer dritten Arbeit (III) erfolgte eine retrospektive Auswertung visueller Parameter im Vergleich von AQP-4-Ak-positiven Patienten und Patienten mit Antikörpern gegen das Myelin-Oligodendrozyten-Glykoprotein (MOG) mittels Optischer Kohärenztomografie (OCT), Visuell Evozierter Potenziale (VEP) und der Fernvisus-Messung. Ergebnisse: Bildmorphologisch zeigte sich in den 7T-T2* gewichteten Aufnahmen bei Patienten mit AQP-4-Ak-positiver NMOSD eine normal große PVA (AQP-4-Ak: PVA = 133 mm2; MS: PVA = 117 mm2; HC: PVA =144 mm2) und überwiegend fehlende paramagnetische Phasenverschiebungen (107 von 112 Läsionen, 96%) in den SWI-Sequenzen. Hinsichtlich des Vergleichs von MOG-Ak- gegenüber von AQP4-Ak-positiven Patienten fiel eine größere absolute Schubrate (Mittelwert, Spannweite, MOG-Ak: 4.5, 1 - 13; APQ4-Ak: 2, 1 -4; p = 0.012), bei insgesamt ähnlichem Verlust der im OCT gemessenen peripapillären retinalen Nervenfaserschicht (pRNFL) der AQP-4-Ak-positiven NMOSD im Vergleich zu den MOG-Ak-positiven Patienten auf (Mittelwert Standardabweichung, MOG-Ak: 59 ± 23 µm, AQP-4-Ak: 59 ± 21 µm). Jedoch waren die Werte der pRNFL nach dem Erstereignis einer ON bei den Patienten mit AQP-4-Ak deutlich stärker reduziert, als bei den MOG-Ak-positiven Patienten (AQP-4-Ak: pRNFL-Verlust = 32.8 μm (p<0.001); MOG-Ak: pRNFL-Verlust = 12.8 μm (p=0.001)). Schlussfolgerung: Mit Hilfe von modernen diagnostischen Verfahren, wie dem Ultrahochfeld-MRT und dem OCT wird die bessere Charakterisierung von phänotypisch ähnlichen neuroinflammatorischen Krankheitsentitäten ermöglicht. Die hierfür zugrundeliegenden unterschiedlichen Pathomechanismen sind bisher nicht vollständig verstanden und bedürfen weiterer Untersuchungen.Introduction: Different neuroinflammatory entities define the group of Neuromyelitis optica spectrum disorders (NMOSD) and are usually associated with the presentation of myelitis and/or optic neuritis. Although various antibodies were verified, there is still the challenge of overlapping clinical and paraclinical phenotypes which ask for further new diagnostic parameters. Methods: By using 7 Tesla (T) magnetic resonance imaging (MRI) patients with aquaporin-4-antibodies (AQP-4-ab) were investigated concerning a) the periventricular venous area (PVA) at T2*-weighted images and b) the phase changes within brain lesions at susceptibility-weighted (SWI)-images. The findings were compared to patients with Multiple Sclerosis (MS) and healthy controls (HC). Further patients with AQP-4-ab and antibodies against myelin oligodendrocyte glycoprotein (MOG-ab) were faced by using retrospective data of retinal optical coherence tomography (OCT), visual acuity and visual evoked potentials (VEP). Results: Patients with AQP-4-ab presented equal results like HC concerning the PVA (AQP-4-ab: PVA = 133 mm2; MS: PVA = 117 mm2; HC: PVA =144 mm2) and predominantly missing phase changes in brain lesions at SWI-images (107 of 112 lesions, 96%). Both, AQP-4-ab- and MOGab-positive patients, presented a loss in peripapillary nerve fiber layer (pRNFL) thickness at the same extend (mean ± standard deviation, MOG-ab: 59 ± 23 ±m, AQP4-ab: 59 ± 21 ±m), while the number of episodes of optic neuritis (ON) was lower in AQP4-ab-positive patients (mean, range, MOG-ab: 4.5, 1 - 13; APQ4-ab: 2, 1 -4; p = 0.012). However, the loss of pRNFL thickness after the first episode of ON was greater in patients with AQP-4-ab (AQP-4-ab: pRNFL-loss = 32.8 µm (p<0.001); MOG-ab pRNFL-loss = 12.8 µm (p=0.001). Conclusion: With the help of novel diagnostic tools, like the ultrahighfield-MRI and OCT, it is possible to distinguish between neuroinflammatory entities with similar phenotypes. For a better understanding of the underlying pathomechanisms further investigations are still needed

Neural Stem Cell Spreading on Lipid Based Artificial Cell Surfaces, Characterized by Combined X-ray and Neutron Reflectometry

We developed a bioadhesive coating based on a synthetic peptide-conjugate (AK-cycloRGDfC]) which contains multiples of the arginyl-glycyl-aspartic acid (RGD) amino acid sequence. Biotinylated AK-cycloRGDfC] is bound to a supported lipid bilayer via a streptavidin interlayer. Layering, hydration and packing of the coating is quantified by X-ray and neutron reflectometry experiments. AK-cycloRGDfC] binds to the streptavidin interlayer in a stretched-out on edge configuration. The highly packed configuration with only 12% water content maximizes the number of accessible adhesion sites. Enhanced cell spreading of neural stem cells was observed for AK-cycloRGDfC] functionalized bilayers. Due to the large variety of surfaces which can be coated by physisorption of lipid bilayers, this approach is of general interest for the fabrication of biocompatible surfaces