Rare KIT (CD117) expression in multiple myeloma abrogates the usefulness of imatinib mesylate treatment

Background: Imatinib mesylate blocks the tyrosine kinase activity of KIT (CD117) and is an effective treatment for gastrointestinal stromal tumors. In multiple myeloma, KIT expression has been detected by flow cytometry in about 33% of specimens, but no previous immunohistochemical assessment has yet been made of the expression pattern of KIT. Materials and methods: We performed immunohistochemical analyses of 100 patients, including 72 with multiple myeloma (MM), 8 with lymphoplasmacytic lymphoma (LPL), 10 with monoclonal gammopathy of undetermined significance (MGUS) and 10 with reactive plasmocytosis. One KIT-positive MM was sequenced using polymerase chain reaction analysis. Results: In MM, only 2 cases (2.8%) were KIT positive. The great majority of the cases (97, 2%) did not express the KIT receptor tyrosine kinase. No mutation of the c-kit gene was detected. Conclusions: KIT expression is a rare event in MM and not detectable in MGUS and LPL. Therefore, treatment with imatinib is unlikely to be effective in these patient

Anesthetic considerations for microlaryngeal surgery

Introduction: Microlaryngeal surgery encompasses a wide range of laryngeal procedures. Patients presenting for microlaryngeal surgery frequently have a difficult airway. The chosen approach to this airway depends on the pathology and the patient’s symptoms. The Aim of the study is to determine the risk factors and anesthetic problems during microlaryngeal surgery.Materials and Methods: A prospective cohort study including 100 patients undergoing microlaryngeal surgery in the Department of Otorhinolaryngology at the University Hospital „Queen Giovanna“ – ISUL, Sofia, in the period 2020–2021; Medical University-Sofia. Preoperative examination of the larynx is performed in all patients by Storz 8402 ZX fiber optic laryngoscope with video capability.Results and discussion: In 69% of the patients the tumor mass causing obstruction is localized in the area of the larynx, and in 31% of them the tumor mass is localized in the area of the hypopharynx. From the patients with tumor mass causing laryngeal obstruction 42% are with 1st degree of obstruction, 29% are with 2nd degree, 27% are with 3rd degree and 2% are with respiratory failure at rest. Twenty six percent (26%) of the patients had pulse rate<45 beats per minute during putting on the tube of Kleinsasser. This is very dangerous reflex reaction of the heart, which we believe is caused by parasympathetic nervous system. The rate of difficult endotracheal intubation among patients presenting for microlaryngeal surgery is higher than among the general surgical patient population. Difficulties during endotracheal intubation in our study are due to higher percent of laryngeal obstruction and pharyngeal restriction because of the intraoral masses.Conclusion: Anesthesia for microlaryngeal surgery has always been demanding, as often pathology interferes with the anesthesiologist’s field of work

Antiproliferative properties against human breast, cervical and ovarian cancer cell lines, and antioxidant capacity of leaf aqueous ethanolic extract from Cotinus coggygria Scop

Cotinus coggygria Scop. leaf aqueous ethanolic extract was examined for its in vitro antiproliferative and antioxidant activity. Antiproliferative effect was assessed on four human gynecological cancer cell lines: breast (MCF7, T47D), cervical (HeLa) and ovarian (A2780) and compared to the cell growth inhibitory effect on non-cancerous breast epithelial cell line MCF10A using MTT cell proliferation assay. Radical scavenging assay with DPPH was applied to evaluate antioxidant potential of the extract. The obtained results showed that the herb inhibited cell growth of all of the tested cancer cell lines and the highest was the cytostatic effect on A2780 cells with a half maximal inhibitory concentration (IC50) value of 30.8 μg/ml. For the other cell lines the IC50 values were in the range of 55-122.7 μg/ml. Additionally, the extract exerted considerably weaker reduction in cell proliferation of the non-cancerous cell line MCF10A compared to cancer cells, which indicates for antiproliferative selectivity. C. coggygria extract showed high free radical scavenging activity with an IC50 value of 11.2 μg/ml. The obtained data provide evidence for pharmacological potential of the tested extract and future more detailed studies concerning the molecular mechanisms of the anticancer effect of the herb are needed

Efficient Synthesis of Fluorescent Coumarins and Phosphorous-Containing Coumarin-Type Heterocycles via Palladium Catalyzed Cross-Coupling Reactions

Quantum-chemical calculations on the spectral properties of some aryl substituted 3- phosphonocoumarins were performed, and the effect of the substituents in the aryl moiety was evaluated. The structures possessing promising fluorescent properties were successfully synthesized via Suzuki and Sonogashira cross-coupling. The synthetic protocol was also applied for the phosphorous chemoisomer of 3-phosphonocoumarin, 1,2-benzoxaphosphorin, and their carboxylate analogues. The optical properties of the arylated and alkynylated products were experimentally determined. The obtained quantum-chemical and experimental results give the possibility for a fine tuning of the optical properties of phosphorous-containing coumarin systems by altering the substituent at its C-6 position

A combined first and second order variational approach for image reconstruction

In this paper we study a variational problem in the space of functions of bounded Hessian. Our model constitutes a straightforward higher-order extension of the well known ROF functional (total variation minimisation) to which we add a non-smooth second order regulariser. It combines convex functions of the total variation and the total variation of the first derivatives. In what follows, we prove existence and uniqueness of minimisers of the combined model and present the numerical solution of the corresponding discretised problem by employing the split Bregman method. The paper is furnished with applications of our model to image denoising, deblurring as well as image inpainting. The obtained numerical results are compared with results obtained from total generalised variation (TGV), infimal convolution and Euler's elastica, three other state of the art higher-order models. The numerical discussion confirms that the proposed higher-order model competes with models of its kind in avoiding the creation of undesirable artifacts and blocky-like structures in the reconstructed images -- a known disadvantage of the ROF model -- while being simple and efficiently numerically solvable.Comment: 34 pages, 89 figure

Impact of SARS-CoV-2 on training and mental well-being of surgical gynecological oncology trainees

Introduction: The SARS-CoV-2 global pandemic has caused a crisis disrupting health systems worldwide. While efforts are being made to determine the extent of the disruption, the impact on gynecological oncology trainees/training has not been explored. We conducted an international survey of the impact of SARS-CoV-2 on clinical practice, medical education, and mental well-being of surgical gynecological oncology trainees. Methods: In our cross-sectional study, a customized web-based survey was circulated to surgical gynecological oncology trainees from national/international organizations from May to November 2020. Validated questionnaires assessed mental well-being. The Wilcoxon rank-sum test and Fisher's exact test were used to analyse differences in means and proportions. Multiple linear regression was used to evaluate the effect of variables on psychological/mental well-being outcomes. Outcomes included clinical practice, medical education, anxiety and depression, distress, and mental well-being. Results: A total of 127 trainees from 34 countries responded. Of these, 52% (66/127) were from countries with national training programs (UK/USA/Netherlands/Canada/Australia) and 48% (61/127) from countries with no national training programs. Altogether, 28% (35/125) had suspected/confirmed COVID-19, 28% (35/125) experienced a fall in household income, 20% (18/90) were self-isolated from households, 45% (57/126) had to re-use personal protective equipment, and 22% (28/126) purchased their own. In total, 32.3% (41/127) of trainees (16.6% (11/66) from countries with a national training program vs 49.1% (30/61) from countries with no national training program, p=0.02) perceived they would require additional time to complete their training fellowship. The additional training time anticipated did not differ between trainees from countries with or without national training programs (p=0.11) or trainees at the beginning or end of their fellowship (p=0.12). Surgical exposure was reduced for 50% of trainees. Departmental teaching continued throughout the pandemic for 69% (87/126) of trainees, although at reduced frequency for 16.1% (14/87), and virtually for 88.5% (77/87). Trainees reporting adequate pastoral support (defined as allocation of a dedicated mentor/access to occupational health support services) had better mental well-being with lower levels of anxiety/depression (p=0.02) and distress (p<0.001). Trainees from countries with a national training program experienced higher levels of distress (p=0.01). Mean (SD) pre-pandemic mental well-being scores were significantly higher than post-pandemic scores (8.3 (1.6) vs 7 (1.8); p<0.01). Conclusion: SARS-CoV-2 has negatively impacted the surgical training, household income, and psychological/mental well-being of surgical gynecological oncology trainees. The overall clinical impact was worse for trainees in countries with no national training program than for those in countries with a national training program, although national training program trainees reported greater distress. COVID-19 sickness increased anxiety/depression. The recovery phase must focus on improving mental well-being and addressing lost training opportunities

Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide

A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0-2 who had completed previous treatment comprising surgical resection, irradiation therapy, and first-line chemotherapy (preferably temozolomide (TMZ) containing regimen) and who have progressed despite treatment. If first-line chemotherapy did not contain TMZ, a second completed chemotherapy was acceptable. The primary efficacy parameter was progression-free survival (PFS). The primary comparison of combination therapy versus monotherapy for PFS was not significant (adjusted P = 0.56). The hazard ratio (HR) (adjusted HR = 0.93) was not clinically relevant. The median PFS for the combination arm was low at 6 weeks and similar to the median PFS in the monotherapy arm (6 weeks). The 6-month PFS for the two treatment groups was very similar (5% in the combination arm vs. 7% in the monotherapy arm). No clinically meaningful differences were found between the two treatment arms, and the primary study end point was not met. Among the patients receiving imatinib, no adverse events were reported that were either previously unknown or unexpected as a consequence of the disease

Sequential dependency for affective appraisal of food images

Abstract How we perceive the world is not solely determined by our experiences at a given moment in time, but also by what we have experienced in our immediate past. Here, we investigated whether such sequential effects influence the affective appraisal of food images. Participants from 16 different countries (N = 1278) watched a randomly presented sequence of 60 different food images and reported their affective appraisal of each image in terms of valence and arousal. For both measures, we conducted an inter-trial analysis, based on whether the rating on the preceding trial(s) was low or high. The analyses showed that valence and arousal ratings for a given food image are both assimilated towards the ratings on the previous trial (i.e., a positive serial dependence). For a given trial, the arousal rating depends on the arousal ratings up to three trials back. For valence, we observed a positive dependence for the immediately preceding trial only, while a negative (repulsive) dependence was present up to four trials back. These inter-trial effects were larger for males than for females, but independent of the participants’ BMI, age, and cultural background. The results of this exploratory study may be relevant for the design of websites of food delivery services and restaurant menus

On the Link between Gaussian Homotopy Continuation and Convex Envelopes

Abstract. The continuation method is a popular heuristic in computer vision for nonconvex optimization. The idea is to start from a simpli-fied problem and gradually deform it to the actual task while tracking the solution. It was first used in computer vision under the name of graduated nonconvexity. Since then, it has been utilized explicitly or im-plicitly in various applications. In fact, state-of-the-art optical flow and shape estimation rely on a form of continuation. Despite its empirical success, there is little theoretical understanding of this method. This work provides some novel insights into this technique. Specifically, there are many ways to choose the initial problem and many ways to progres-sively deform it to the original task. However, here we show that when this process is constructed by Gaussian smoothing, it is optimal in a specific sense. In fact, we prove that Gaussian smoothing emerges from the best affine approximation to Vese’s nonlinear PDE. The latter PDE evolves any function to its convex envelope, hence providing the optimal convexification