Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Τετάρτη 28 Οκτωβρίου 2020

Characterization of Circular RNA Transcriptomes in Psoriasis and Atopic Dermatitis Reveals Disease‐specific Expression Profiles

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Abstract

Atopic dermatitis (AD) and psoriasis, two common chronic inflammatory skin diseases that are associated with various comorbidities. Circular RNA (circRNA) constitute a major class of non‐coding RNAs that have been implicated in many human diseases, although their potential involvement in inflammatory skin diseases remains elusive. Here, we compare and contrast the circRNA expression landscapes in paired lesional and non‐lesional skin from psoriasis and AD patients relative to skin from unaffected individuals using high‐depth RNA‐seq data. CircRNAs and their cognate linear transcripts were quantified using the circRNA detection algorithm, CIRI2, and in situ hybridization and Sanger sequencing was used for validation purposes. We identified 39,286 circRNAs among all samples and found that psoriasis and AD lesional skin could be distinguished from non‐lesional and healthy skin based on circRNA expression landscapes. In general, circRNAs were less abundant in lesional relati ve to non‐lesional and healthy skin. Differential expression analyses revealed many significantly downregulated circRNAs, mainly in psoriasis lesional skin, and a strong correlation between psoriasis and AD‐related circRNA expression changes was observed. Two individual circRNAs, ciRS‐7 (also known as CDR1as) and circZRANB1, was specifically dysregulated in psoriasis and show promise as biomarkers for discriminating AD from psoriasis. In conclusion, the circRNA transcriptomes of psoriasis and AD share expression features, including a global downregulation relative to healthy skin, but this is most pronounced in psoriasis, and only psoriasis is characterized by several circRNAs being dysregulated independently of their cognate linear transcripts. Finally, specific circRNAs could potentially be used to distinguish AD from psoriasis.

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The Erythema Q‐score, an Imaging Biomarker for Redness in Skin Inflammation

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Abstract

Background

Physician rating of cutaneous erythema is central to clinical dermatological assessment as well as quantification of outcome measures in clinical trials in a number of dermatologic conditions. However, issues with interrater reliability and variability in the setting of higher Fitzpatrick skin types makes visual erythema assessment unreliable.

Aim

To develop and validate a computer‐assisted image‐processing algorithm (EQscore) to reliably quantify erythema (across a range of skin types) in the dermatology clinical setting.

Methods

An image processing algorithm (EQscore) was developed to evaluate erythema based upon green‐light suppression differentials between affected and unaffected skin. A group of 4 dermatologists used a 4‐point Likert scale as a human evaluation of similar erythematous patch tests. Algorithm and dermatologist scores were compared across 164 positive patch test reactions. The intra‐class correlation coefficient of groups and the correlation coefficient between groups were calculated. The EQscore was validated on and independent image set of psoriasis, minimal erythema dose testing, and steroid‐induced blanching images.

Results

The reliability of the erythema quantification method produced an intra‐class correlation coefficient of 0.84 for the algorithm and 0.67 for dermatologists. The correlation coefficient between groups was 0.85. The EQscore was able to quantify erythema.

Conclusion

The EQscore demonstrated high agreement with clinical scoring and superior reliability compared with clinical scoring, avoiding the pitfalls of erythema underrating in the setting of pigmentation. The EQscore is easily accessible, user‐friendly, and may allow dermatologists to more readily and accurately rate the severity of dermatological conditions and the response to therapeutic treatments.

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The inflammation in cutaneous lichen planus is dominated by IFN‐ϒ and IL‐21 – a basis for therapeutic JAK1 inhibition

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Abstract

Cutaneous lichen planus (CLP) and psoriasis (PSO) are both common chronic inflammatory skin diseases for which development of new treatments requires the identification of key targets. While PSO is a typical Th17/IL‐17‐disorder, there is some evidence that Th1/IFN‐ɣ dominate the inflammatory process in CLP. Nonetheless, the immunopathogenesis of CLP is not fully explained and key immunological factors still have to be recognized. In this study, we compared the immune signature of CLP lesions with the well characterized inflammation present in PSO skin. First, we analyzed the histological and immunohistological characteristics of CLP and PSO. Second, we assessed the cytokine expression (IL1A, IL1B, IL4, IL6, IL8, IL10, IL17A, IL19, IL21, IL22, IL23A, IL13, IFNG, TNF, IL12A, IL12B, IL36G) of lesional skin of CLP with PSO by qPCR. Histology revealed a similar epidermal thickness in CLP and PSO. Immunohistochemically, both diseases presented with an inflammatory infiltra te mainly composed by CD3+CD4+ T cells rather than CD3+CD8+. Importantly, mRNA analysis showed a distinct cytokine signature: while levels of IL12B, IL1A, IL6 and IL23 were similar between the two groups, the characteristic PSO‐associated cytokines IL8, IL17A, IL22, IL19 and IL36G were expressed at very low levels in CLP. In contrast, CLP lesional skin was dominated by the expression of IFNG, IL21, IL4, IL12A, and TNF. Immunohistochemistry confirmed the dominance of IL‐21, IFN‐ɣ and also pSTAT1 in the dermal infiltrate of CLP, while IL‐17A was more present in PSO. Collectively, this study improves our understanding of the immunological factors dominating CLP. The dominating cytokines and signaling proteins identified suggest that future anti‐cytokine therapeutics like JAK inhibitors may be beneficial in CLP.

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Immersive Virtual Environments and Wearable Haptic Devices in rehabilitation of children with neuromotor impairments: a single-blind randomized controlled crossover pilot study

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The past decade has seen the emergence of rehabilitation treatments using virtual reality. One of the advantages in using this technology is the potential to create positive motivation, by means of engaging en...
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Kigelia africana (Lam.) Benth. fruit extracts in diabetes mellitus

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Abstract

The use of Kigelia africana plant is beneficial in many medicinal applications. This study investigated the chemical compounds as well as antioxidant and antidiabetic activities of KA fruits in vitro and in vivo. Molecular docking study was used to predict the activities of these metabolites in relation to diabetes mellitus. From the result of GC-qTOF-MS, phenol-2,4-bis(1,1-dimethylethyl)-, benzene propanoic acid-3,5-bis(1,1-dimethylethyl)-4-hydroxymethylester, naphthalene-2-methyl-, and oxalic acid-4-chlorophenyl nonyl-ester were newly identified and revealed a strong binding affinity of − 6.1, − 6.3, − 6.8, and − 6.2 kcal/mol respectively. The hexane and ethyl acetate fractions had the highest antioxidant activities with 0.14 and 0.025 mg/mL for DPPH; 91.31 and 99.20 mg AAE/g for FRAP; and 80.61 and 98.88 mg AAE/g for TPC, respectively. Hexane fraction (HF) had the lowest IC50 value (1.97 mg/mL) against α-amylase. At low and middle doses, HF showed significant ameliorative activities by restoring islet cells, increasing the number of β cells, and reducing fasting blood glucose levels. Significant differences were observed in the activities of GGT and G-6-PDH. KA fruit exhibited high antidiabetic and antihyperglycemic activities in STZ-induced diabetic rats. According to molecular docking study, the use of the base structure of 2,4-ditert-butylphenol identified from K. africana fruit may serve as the novel approach to the treatment of diabetes mellitus.

Graphical abstract

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Mitochondrial cardiomyopathy caused by the mitochondrial DNA mutation m.3243A > G

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Abstract

Mitochondrial cardiomyopathy can be described as a condition characterized by abnormal heart-muscle structure and/or function, secondary to mutations in nuclear or mitochondrial DNA. Its severity can range from subclinical to critical conditions. We presented three cases of mitochondrial cardiomyopathy with m.3243A > G mutation and compared the clinical manifestations with the histological findings for each of these cases. All cases showed cardiac hypertrophy, juvenile-onset diabetes mellitus, and hearing loss. Case 1 (43-year-old male) showed less cardiac involvement and shorter duration of mitochondrial disease-related symptoms than case 2 (67-year-old female) and case 3 (51-year-old male), who showed the most advanced cardiac condition and longest duration from the manifestation of heart failure. The histological findings revealed that cardiomyocytes from case 1 showed no hypertrophy and mitochondrial degeneration in electron microscopy. Alternatively, cases 2 and 3 showed hypertrophy in their cardiomyocytes, and mitochondrial degeneration (e.g. onion-like lesions, swollen cristae, and lamellar bodies) was most apparent in case 3. These results suggested that mitochondrial degeneration, as evaluated by electron microscopy, might be correlated with impaired heart function in patients with mitochondrial cardiomyopathy.

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Photosensitivität unter Vemurafenib

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Zusammenfassung

Vemurafenib, ein BRAF‐Inhibitor, weist als häufige kutane Nebenwirkung eine erhöhte Photosensitivität auf, die sich klinisch im Auftreten eines sofortigen Hitzegefühls und eines ödematösen Erythems bei Sonnenexposition sowie einer Sonnenbrandreaktion im Sinne einer Spätreaktion äußert. Phototestungen konnten sowohl für die Sofortreaktion als auch für die Spätreaktion ein Aktionsspektrum im UVA‐Bereich (320 nm bis 400 nm) belegen. Pathogenetisch legten photochemische Untersuchungen nahe, dass UVA‐Bestrahlung von Vemurafenib unter bestimmten Bedingungen ein UVA‐absorbierendes Photoprodukt produziert. Auch in vitro konnte an verschiedenen Zellmodellen die phototoxische Wirkung von Vemurafenib ausschließlich im UVA‐Bereich nachgewiesen werden. Bei der klinisch zu beobachtenden Lichtempfindlichkeit dominiert wahrscheinlich dieser Mechanismus.

Andererseits kann Vemurafenib zusätzlich die Ferrochelatase inhibieren, was zu einem Anstieg von Protoporphyrin IX führt, der auch in einigen Untersuchungen beim Menschen unter Einnahme von Vemurafenib nachgewiesen wurde. Ob die Porphyrine tatsächlich insbesondere zur Symptomatik der Sofortreaktion beitragen, die klinisch der erythropoetischen Protoporphyrie (EPP) mit einem vergleichbaren Pathomechanismus ähnelt, ist noch nicht abschließend geklärt.

Andere BRAF‐Inhibitoren wie Dabrafenib und Encorafenib weisen eine deutliche geringere Photosensitivität auf. Patienten, die mit Vemurafenib therapiert werden, müssen auf die bereits durch geringe UVA‐Dosen auslösbaren Sofort‐ und Spätreaktionen hingewiesen werden und hinsichtlich photoprotektiver Maßnahmen beraten werden.

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Moderne Therapie der atopischen Dermatitis: Biologika und kleinmolekulare Medikamente

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Zusammenfassung

Die atopische Dermatitis ist eine der häufigsten chronisch entzündlichen Hauterkrankungen. Die Pathomechanismen der atopischen Dermatitis wurden in den letzten Jahren immer besser verstanden. Dies kann zukünftig dazu beitragen, verschiedene Endotypen zu identifizieren, die für bestimmte Therapien bevorzugt geeignet sind. Eine patientenadaptierte Therapie berücksichtigt neben dem phänotypischen Erscheinungsbild genetische und biologische Merkmale. Die aktuelle Entwicklung von Biologika und kleinmolekularen Medikamenten zur Behandlung der atopischen Dermatitis wird im vorliegenden Artikel vorgestellt. Diese Moleküle werden, wenn sie zugelassen werden, die Therapieperspektiven in der Zukunft verändern.

Dupilumab ist als erstes Biologikum bereits zur Behandlung der atopischen Dermatitis bei Jugendlichen und Erwachsenen zugelassen und hat die Behandlung von Patienten mit mittelschwerer und schwerer atopischer Dermatitis verbessert. In der vorliegenden Arbeit werden eigene Real‐Life‐Daten zur Wirksamkeit von Dupilumab bei der atopischen Dermatitis vorgestellt. Darüber hinaus werden weitere relevante Daten gezeigt, die in der praktischen Anwendung von Dupilumab eine Rolle spielen, und offene Fragen werden diskutiert.

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Pilotstudie zum Einfluss von kaltem atmosphärischem Plasma auf bakterielle Kontamination und Heilungstendenz chronischer Wunden

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Zusammenfassung

Hintergrund

Wöchentlich dreimalige Anwendung kalten atmosphärischen Plasmas (KAP) wurde bereits erfolgreich zur Wundbehandlung eingesetzt. Jetzt sollte untersucht werden, ob mit nur einmal wöchentlicher Behandlung vergleichbar gute Ergebnisse erzielt werden können.

Patienten und Methodik

In dieser randomisierten klinischen Pilotstudie (RCT) wurden Patienten mit therapierefraktären chronischen Wunden über maximal zwölf Wochen 1 x/Woche (Gruppe 1) oder 3 x/Woche (Gruppe 2) mit KAP behandelt. Patienten der Gruppe 3 erhielten 1 x/Woche eine Placebotherapie.

Ergebnisse

Die Wundfläche nahm in Gruppe 1 (n = 14) signifikant um 63,0 % (P = 0,005) und in Gruppe 2 (n = 13) um 46,8 % (P = 0,007) ab. In Gruppe 3 (n = 10) wurden die Wunden durchschnittlich 17,5 % größer. In den beiden mit KAP behandelten Gruppen konnte eine signifikante Schmerzreduktion (Gruppe 1: P = 0,042; Gruppe 2: P = 0,027) gemessen werden. Ausschließlich in der Gruppe 2 zeigte sich eine signifikante Verbesserung der wundspezifischen Lebensqualität (P = 0,005). Nach der zwölfwöchigen KAP‐Behandlung konnte eine Reduktion der Bakterienlast um durchschnittlich 50,4 % (Gruppe 1) beziehungsweise um 35,0 % (Gruppe 2) im Vergleich zum Tag des Studieneinschlusses nachgewiesen werden.

Schlussfolgerungen

Unserer RCT zeigt, dass durch die Behandlung mit KAP verschiedene Parameter der Wundheilung bei Patienten mit therapierefraktären, chronischen Wunden verbessert werden. Hierbei waren die Ergebnisse bei der Anwendung 1 x/Woche der Anwendung 3 x/Woche nicht unterlegen. Die Behandlung 1 x/Woche ist im klinischen Alltag leichter und wirtschaftlicher zu implementieren.

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Comparative accuracy of cone‐beam CT and conventional multislice computed tomography for real‐time navigation in zygomatic implant surgery

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Abstract

Background

Cone‐beam computed tomography (CBCT) and conventional multislice CT (MSCT) are both used in zygomatic implant navigation surgery but the superiority of one technique versus the other remains unclear.

Purpose

This study compared the accuracy of CBCT and MSCT in zygomatic implant navigation surgery by calculating the deviations of implants.

Material and methods

Patients with severely atrophic maxillae were classified into two groups according to the use of CBCT‐ or MSCT‐guided navigation system. The entry and apical distance deviation, and the angle deviation of zygomatic implants were measured on fused operation images. A linear effect model was used for analysis, with statistical significance set at P < .05.

Results

A total of 72 zygomatic implants were inserted as planned in 23 patients. The comparison of deviations in CBCT and MSCT groups showed a mean (± SD) entry deviation of 1.69 ± 0.59 mm vs 2.04 ± 0.78 mm (P = .146), apical deviation of 2 ± 0.68 mm vs 2.55 ± 0.85 (P < .001), and angle deviation of 2.32 ± 1.02° vs 3.23 ± 1.21° (P = .038).

Conclusion

Real‐time zygomatic implant navigation surgery with CBCT may result in higher values for accuracy than MSCT.

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The right thalamic ventral posterolateral nucleus seems to be determinant for macrosomatognosia: a case report

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Abstract

Background

Macrosomatognosiais the illusory sensation of a substantially enlarged body part. This disorder of the body schema, also called "Alice in wonderland syndrome" is still poorly understood and requires careful documentation and analysis of cases. The patient presented here is unique owing to his unusual macrosomatognosia phenomenology, but also given the unreported localization of his most significant lesion in the right thalamus that allowed consistent anatomo-clinical analysis.

Case presentation

This 45-years old man presented mainly with long-lasting and quasi-delusional macrosomatognosia associated to sensory deficits, both involving the left upper-body, in the context of a right thalamic ischemic lesion most presumably located in the ventral posterolateral nucleus. Fine-grained probabilistic and deterministic tractography revealed the most eloquent targets of the lesion projections to be the ipsilateral precuneus, superior parietal lobule,but also the right primary somatosensory cortex and, to a lesser extent, the right primary motor cortex. Under stationary neurorehabilitation, the patient slowly improved his symptoms and could be discharged back home and, later on, partially return to work.

Conclusion

We discuss deficient neural processing and integration of sensory inputs within the right ventral posterolateral nucleus lesion as possible mechanisms underlying macrosomatognosia in light of observed anatomo-clinical correlations. On the other hand, difficulty to classify this unique constellation of Alice in wonderland syndrome calls for an alternative taxonomy of cognitive and psychic aspects of illusory body-size perceptions.

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Effect of vitamin A, calcium and vitamin D fortification and supplementation on nutritional status of women: an overview of systematic reviews

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Micronutrient deficiency affects the health and development of vulnerable population such as children and pregnant women. Measures such as fortification of food and supplementation have been implemented to pre...
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