Cyclodextrin enhances corneal tolerability and reduces ocular toxicity caused by diclofenac

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with β-, γ-, and HP-β-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-β-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-β-CD demonstrated fast healing without scar formation

Requirements Analysis for an Open Research Knowledge Graph

Current science communication has a number of drawbacks and bottlenecks which have been subject of discussion lately: Among others, the rising number of published articles makes it nearly impossible to get an overview of the state of the art in a certain field, or reproducibility is hampered by fixed-length, document-based publications which normally cannot cover all details of a research work. Recently, several initiatives have proposed knowledge graphs (KGs) for organising scientific information as a solution to many of the current issues. The focus of these proposals is, however, usually restricted to very specific use cases. In this paper, we aim to transcend this limited perspective by presenting a comprehensive analysis of requirements for an Open Research Knowledge Graph (ORKG) by (a) collecting daily core tasks of a scientist, (b) establishing their consequential requirements for a KG-based system, (c) identifying overlaps and specificities, and their coverage in current solutions. As a result, we map necessary and desirable requirements for successful KG-based science communication, derive implications and outline possible solutions.Comment: Accepted for publishing in 24th International Conference on Theory and Practice of Digital Libraries, TPDL 202

Energy Restriction during Childhood and Early Adulthood and Ovarian Cancer Risk

Dietary energy restriction may protect against cancer. In parts of the Netherlands, mostly in larger cities, periods of chronically impaired nutrition and even severe famine (Hunger Winter 1944–1945) existed during the 1930s and World War II (1940–1945). We studied the association between energy restriction during childhood and early adulthood on the risk of ovarian cancer later in life. In 1986, the Netherlands Cohort Study was initiated. A self-administered questionnaire on dietary habits and other cancer risk factors was completed by 62,573 women aged 55–69 years at baseline. Follow-up for cancer was established by record linkage to the Netherlands Cancer Registry. After 16.3 years of follow-up, 364 invasive epithelial ovarian cancer cases and 2220 subcohort members (sampled from the total cohort directly after baseline) with complete information confounders were available for case-cohort analyses. In multivariable analysis, ovarian cancer risk was lower for participants with an unemployed father during the 1930s (Hazard Ratio (HR), 0.70; 95% Confidence Interval (CI), 0.47–1.06) compared to participants with an employed father as well as for participants living in a city during World War II (HR, 0.69; 95% CI, 0.54–0.90) compared to participants living in the country-side. Residence in a Western City during the famine (Hunger Winter) was not associated with a decreased risk. Our results show a relation between proxy variables for modest energy restriction over a longer period of time during childhood or early adulthood and a reduced ovarian cancer risk

ICAR: endoscopic skull‐base surgery

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Synthesis and Molecular Docking of Some Novel 3-Thiazolyl-Coumarins as Inhibitors of VEGFR-2 Kinase

One crucial strategy for the treatment of breast cancer involves focusing on the Vascular Endothelial Growth Factor Receptor (VEGFR-2) signaling system. Consequently, the development of new (VEGFR-2) inhibitors is of the utmost importance. In this study, novel 3-thiazolhydrazinylcoumarins were designed and synthesized via the reaction of phenylazoacetylcoumarin with various hydrazonoyl halides and α-bromoketones. By using elemental and spectral analysis data (IR, 1H-NMR, 13C-NMR, and Mass), the ascribed structures for all newly synthesized compounds were clarified, and the mechanisms underlying their formation were delineated. The molecular docking studies of the resulting 6-(phenyldiazenyl)-2H-chromen-2-one (3, 6a–e, 10a–c and 12a–c) derivatives were assessed against VEGFR-2 and demonstrated comparable activities to that of Sorafenib (approved medicine) with compounds 6d and 6b showing the highest binding scores (−9.900 and −9.819 kcal/mol, respectively). The cytotoxicity of the most active thiazole derivatives 6d, 6b, 6c, 10c and 10a were investigated for their human breast cancer (MCF-7) cell line and normal cell line LLC-Mk2 using MTT assay and Sorafenib as the reference drug. The results revealed that compounds 6d and 6b exhibited greater anticancer activities (IC50 = 10.5 ± 0.71 and 11.2 ± 0.80 μM, respectively) than the Sorafenib reference drug (IC50 = 5.10 ± 0.49 μM). Therefore, the present study demonstrated that thiazolyl coumarins are potential (VEGFR-2) inhibitors and pave the way for the synthesis of additional libraries based on the reported scaffold, which could eventually lead to the development of efficient treatment for breast cancer

Revisiting the harem conspiracy and death of Ramesses III : Anthropological, forensic, radiological, and genetic study

Objective: To investigate the true character of the harem conspiracy described in the Judicial Papyrus of Turin and determine whether Ramesses III was indeed killed. Design: Anthropological, forensic, radiological, and genetic study of the mummies of Ramesses III and unknown man E, found together and taken from the 20th dynasty of ancient Egypt (circa 1190-1070 BC). Results: Computed tomography scans revealed a deep cut in Ramesses III's throat, probably made by a sharp knife. During the mummification process, a Horus eye amulet was inserted in the wound for healing purposes, and the neck was covered by a collar of thick linen layers. Forensic examination of unknown man E showed compressed skin folds around his neck and a thoracic inflation. Unknown man E also had an unusual mummification procedure. According to genetic analyses, both mummies had identical haplotypes of the Y chromosome and a common male lineage. Conclusions: This study suggests that Ramesses III was murdered during the harem conspiracy by the cutting of his throat. Unknown man E is a possible candidate as Ramesses III's son Pentawere.</p