Evaluation of Oleogels Stabilized by Particles of Birch Outer Bark Extract through a Novel Approach.

Structuring liquid oils into oleogels using natural and abundant biomass components as gelling agents is of great significance in fields such as foods, pharmaceuticals, and cosmetics. In this work, a more energy-efficient and technologically simpler approach for directly preparing birch outer bark extract particles containing oleogel was used. This method involves introducing birch outer bark extract particles into the oil phase directly from the extract solution, combining both the evaporation of solution and gel formation. As a result, stable oleogels of various vegetable oils (sunflower, almond, olive, and hemp seed) were obtained with birch outer bark extract particle contents of 4-10%. Infrared spectroscopy and particle size analysis confirmed that when increasing the content of extract particles in the oil, increasing self-assembly of extract particles via hydrogen bonding occurs, leading to the formation of a more structured network. This is consistent with gel strength values from rheological tests of oleogels, which also increased with particle concentration. The obtained oleogels showed important properties such as good tolerance to time-dependent deformation, shear thinning, and thermoreversibility.

Evaluation of Post-Larval Diets for Indoor Weaned Largemouth Bass (Micropterus salmoides).

This study aimed to evaluate different commercial diets (Otohime C1, Aller Futura (AF), Biomar Inicio Plus (BIP)) and one experimental feed (EF) in terms of their effectiveness as post-larval diets for indoor weaned largemouth bass, LMB (Micropterus salmoides). Key variations in the content of nutritive values were monounsaturated fatty acid (MUFA) and highly unsaturated FA (HUFA) ω3. Fish were fed with one of four tested diets from the 33rd to the 40th day post-hatch (DPH). Biometric indices, digestive enzyme-specific activities, thyroid hormone status, and mRNA expression of genes coding for skeleton, neuron, and muscle growth were analyzed. The lowest skeletal deformity rate and highest survival among the treatments were seen in BIP-fed fish. Dietary lipids, with an appropriate balance between MUFA and polyunsaturated FA (PUFA), alongside amino acid balance, were shown to be the main contributors to the growth of the skeleton and/or fish survival. On the other hand, fish growth is correlated with fish digestive capacity and feed moisture percent rather than feed quality. Unexpectedly, BIP-fed fish were attributed with the lowest expression of skeleton differentiation markers, which may reflect the sacrifice of scale and/or cranium growth at the expense of somatic growth. This study highlights the role of non-marine ingredients in the nutrition of post-larval LMB.

Chemical Profiling and Antioxidant Activity of Tanacetum vulgare L. Wild-Growing in Latvia.

The Tanacetum vulgare L. (Tansy) has several ethnobotanical uses, mostly related to the essential oil and sesquiterpene lactones, whereas information regarding other compounds is scarce. This research is designed to characterize the phenolic compounds (flavonoids, phenolic acids, and tannins) to analyze the thujone (which is toxic in high concentrations) content and to detect the antioxidant activity (DPPH assay) of extracts. The main highlights of our work provide a chemical profile of phenolic compounds of T. vulgare harvested from different regions of Latvia, as well as simultaneously support the ethnomedicinal uses for wild T. vulgare through the integration of phenolic compounds as one of the value constituents of leaves and flowers. The extraction yield was 18 to 20% for leaves and 8 to 16% for flowers. The total phenol content in the extracts of T. vulgare as well as their antioxidant activity was different between collection regions and the aerial parts ranging from 134 to 218 mg GAE/g and 32 to 182 mg L-1, respectively. A remarkable variation in the thujone (α + ß) content (0.4% up to 6%) was detected in the extracts. T. vulgare leaf extracts were rich in tannins (up to 19%). According to the parameters detected, the extracts of T. vulgare could be considered promising for the development of new herbal products.

Impact of neoadjuvant FLOT treatment of advanced gastric and gastroesophageal junction cancer following surgical therapy.

Introduction: Therapeutic treatment for advanced-stage (T2-T4) gastroesophageal junction (GEJ) and gastric cancer involves neoadjuvant chemotherapy with subsequent surgical intervention. Method: Neoadjuvant oncological treatment for GEJ and gastric cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group 1). The new protocol (FLOT, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), included patients with resectable GEJ and gastric cancer who had a clinical stage cT2 or higher nodal positive cN+ disease (Group 2). Between 31 December 2008 and 31 October 2022, the effect of different oncological protocols in terms of surgical outcomes in cases of T2-T4 tumours were retrospectively evaluated. Results of randomly assigned patients from the earlier ECF/ECX protocol (n = 36) (Group 1) and the new FLOT protocol (n = 52) (Group 2) were compared. Effect of different neoadjuvant therapies on tumour regression, types of possible side effects, type of surgery, and oncological radicality of surgical procedures were analysed. Results: When comparing the two groups, we found that in case of the FLOT neoadjuvant chemotherapy (Group 2, n = 52), complete regression was achieved in 13.95% of patients, whereas in the case of ECF/ECX (Group 1, n = 36), complete regression occurred in only 9.10% of patients. Furthermore, in the FLOT group, the mean number of lymph nodes removed was slightly higher (24.69 vs. 20.13 in the ECF/ECX group). In terms of the safety resection margin (proximal), no significant difference was found between the two treatment groups. Nausea and vomiting were the most common side effects. The occurrence of diarrhea was significantly higher in the FLOT group (p = 0.006). Leukopenia and nausea occurred more commonly with the old protocol (Group 1). The rate of neutropenia was lower following FLOT treatment (p = 0.294), with the lack of grade II and III cases. Anaemia occured at a significantly higher rate (p = 0.036) after the ECF/ECX protocol. Conclusions: As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-esophageal junction and gastric cancer, the rate of complete tumour regression increased significantly. The rate of side effects was also appreciably lower following the FLOT protocol. These results strongly suggest a significant advantage of the FLOT neoadjuvant treatment used before surgery.

The impact of the first wave of COVID-19 on students' attainment, analysed by IRT modelling method.

Universities around the world were closed for several months to slow down the spread of the COVID-19 pandemic. During this crisis, a tremendous amount of effort was made to use online education to support the teaching and learning process. The COVID-19 pandemic gave us a profound insight into how online education can radically affect students and how students adapt to new challenges. The question is how switching to online education affected dropout? This study shows the results of a research project clarifying the impact of the transition to online courses on dropouts. The data analysed are from a large public university in Europe where online education was introduced in March 2020. This study compares the academic progress of students newly enroled in 2018 and 2019 using IRT modelling. The results show that (1) this period did not contribute significantly to the increase in dropout, and we managed to retain our students.(2) Subjects became more achievable during online education, and students with less ability were also able to pass their exams. (3) Students who participated in online education reported lower average grade points than those who participated in on-campus education. Consequently, on-campus students could win better scholarships because of better grades than students who participated in online education. Analysing students' results could help (1) resolve management issues regarding scholarship problems and (2) administrators develop programmes to increase retention in online education.

Nursing of Pike-Perch (Sander lucioperca) in Recirculating Aquaculture System (RAS) Provides Growth Advantage in Juvenile Growth Phase.

This study aimed to estimate the efficacy of two pike-perch juvenile production technologies: exclusive Recirculating Aquaculture System (RAS) culture (the RAS group) and pond larviculture with a transfer to the RAS at the 42nd day post-hatch (DPH). Both direct weaning on dry feed (the Pond-D group) and 10-day gradual weaning using bloodworms (the Pond-B group) after transfer to the RAS were evaluated in pond-nursed fry. Their survival and morphometric indices were monitored after the RAS habituation period (first 10 days), after the 18-day post-habituation period and after an additional 30 days of on-grow. Our results indicate a negative allometric growth of the pond-nursed fish during the nursing period, which was slower (p < 0.0001) in comparison to the RAS-nursed fry (16.3 ± 0.4 vs. 17.8 ± 0.7%/day). After transfer, these fish grew faster than the RAS-nursed fry (7.7 ± 0.1, 4.9 ± 0.5 and 6.1 ± 0.6 during habituation, 8.5 ± 0.6, 9.3 ± 0.5 and 6.7 ± 0.1%/day during post-habituation period, in the Pond-B, Pond-D and RAS groups, respectively). However, four weeks afterwards, the RAS-nursed fry were again superior in terms of growth (4.0 ± 0.1, 3.6 ± 0.2 and 4.6 ± 0.2%/day, for the Pond-B, Pond-D and RAS groups, respectively), and this was accompanied by a significantly lower feed conversion ratio in this group. Although the survival of the RAS-nursed fry during the nursing period was lower in comparison to the pond-reared fry (11.3 vs. 67.3%), the RAS seems to provide a long-term growth advantage.

Surgical treatment of gastroesophageal reflux disease and Barrett's esophagus / A gastro-oesophagealis refluxbetegség és a Barrett-nyelocso sebészi kezelése

For the centenary of the Department of Surgery, University of Szeged we have investigated and summarized the results and outcomes of 779 anti-reflux surgery cases between 1. January 2000 ­ 31. May 2021. The indication for surgery was made in close collaboration with the internal medicine workgroup depending on the results of endoscopy and functional tests. The primer indication for surgery was medical therapy-resistant reflux disease. Based on our clinical practice we performed laparoscopic Nissen fundoplication in 98,2% of the cases. Besides the long- and short-term postoperative complications, we investigated the long-term effect of anti-reflux surgery on acid and bile reflux, and the improvement of the patients' quality of life using the Visick score, and modified GERD-HRLQ score. Our investigations have proven the effect of acid and bile reflux in the pathogenesis of Barrett's esophagus and furthermore we have confirmed that laparoscopic anti-reflux surgery restores the function of the lower esophageal sphincter and eliminates acid and bile reflux, so in certain cases Barrett's esophagus regression can be achieved. But due to the heterogeneity of GERD and Barrett's esophagus long-term and regular endoscopic control is necessary.

New trends in the surgical treatment of axilla in breast cancer / Új trendek az axilla sebészi kezelésében emlorák esetén

Oncosurgical treatment of breast tumors involves the removal of metastatic axillary lymph nodes. In the last 30 years, the diagnosis and treatment of axillary lymph nodes have also undergone significant changes. The introduction of sentinel lymph node biopsy in 1993 made axillary block dissection with high morbidity safely omitted in a significant proportion of patients, and similarly, the staging of breast tumors and thus oncology and complex treatment became significantly more accurate. Shortly after the introduction of sentinel lymph node biopsy, intraoperative examination of sentinel lymph nodes (e.g. imprint cytology) also appeared, which significantly reduced the number of surgeries performed in the two sessions, thereby significantly reducing patient burden and surgical costs. The results of our study indicate that axillary block dissection is required in the treatment of axilla in an ever-decreasing group of patients and this proportion will decrease further in the future, with the increasing use of alternative axillary radiotherapy. The imprint cytological examination of sentinel lymph nodes taking into account current guidelines, no longer provides demonstrable benefits and its routine use is not justified. According to the latest international recommendations, intraoperative examination of the sentinel lymph node may be indicated in connection with mastectomy (when postoperative radiotherapy is not planned) and after neoadjuvant treatment. Our results suggest that the detection of suspected lymph nodes during preoperative axillary ultrasound may predict the stage of the disease. Based on our research results confirm that in patients receiving neoadjuvant therapy, in addition to the preoperative size of the tumour (≤20 mm, P = 0.002), the preoperative size of the lymph node (≤15 mm, P = 0.04) may also be used to predict that the stage of the disease is N0-1.

Localization of macroscopically undetectable intramedullary hematoma by intraoperative epidural motor evoked potential.

Introduction: Intramedullary hematoma is an uncommon, serious neurological disease, representing a diagnostic challenge. The preferred treatment is surgical. In most of the cases the lesion can be identified macroscopically. Otherwise, finding the optimal place to perform myelotomy is demanding. Intraoperative neurophysiological monitoring plays an important role in preventing surgical complications, but its versatility for localization has not been studied so far. Case report: The present case report describes a 17-year-old patient with flaccid right inferior monoparesis (later paraparesis), ipsilateral loss of proprioception and vibration sense, contralateral analgesia below the T10 dermatome level and urinary retention (Brown-Séquard syndrome). The MRI revealed an intramedullary hematoma at the level of T8-T9 vertebral bodies. Digital subtraction angiography did not identify any vascular malformation. Urgent surgical intervention was performed. In order to prevent any complication somatosensory-evoked potential (SSEP), transcranial and epidural motor-evoked potential (tcMEP, eMEP) recordings were planned. SSEP in response to right tibial nerve stimulation and tcMEP were absent bilaterally. From electrophysiological point of view, the eMEP revealed a total conduction block of the corticospinal tract. In the absence of typical macroscopic signs (discoloration, swelling, abnormal vascularization etc.), the small intramedullary hematoma could not be identified. Therefore, it was decided to adopt eMEP technique for mapping and localizing the conduction block intraoperatively by changing the distance between the two electrodes used for recording. The hematoma was precisely localized and successfully evacuated. Postoperatively, a slow but continuous improvement was noted. Conclusion: Intraoperative neurophysiological monitoring has been suggested to play crucial role in spinal cord surgery. To our knowledge, this is the first case report using eMEP recording for guiding and localizing of an intramedullary hematoma. Beside the clear limitations of our study, it could result in a novel application of the aforementioned monitoring technique.

Artificial Intelligence-Based Colorectal Polyp Histology Prediction by Using Narrow-Band Image-Magnifying Colonoscopy.

BACKGROUND/AIMS: We have been developing artificial intelligence based polyp histology prediction (AIPHP) method to classify Narrow Band Imaging (NBI) magnifying colonoscopy images to predict the hyperplastic or neoplastic histology of polyps. Our aim was to analyze the accuracy of AIPHP and narrow-band imaging international colorectal endoscopic (NICE) classification based histology predictions and also to compare the results of the two methods. METHODS: We studied 373 colorectal polyp samples taken by polypectomy from 279 patients. The documented NBI still images were analyzed by the AIPHP method and by the NICE classification parallel. The AIPHP software was created by machine learning method. The software measures five geometrical and color features on the endoscopic image. RESULTS: The accuracy of AIPHP was 86.6% (323/373) in total of polyps. We compared the AIPHP accuracy results for diminutive and non-diminutive polyps (82.1% vs. 92.2%; p=0.0032). The accuracy of the hyperplastic histology prediction was significantly better by NICE compared to AIPHP method both in the diminutive polyps (n=207) (95.2% vs. 82.1%) (p<0.001) and also in all evaluated polyps (n=373) (97.1% vs. 86.6%) (p<0.001). CONCLUSION: Our artificial intelligence based polyp histology prediction software could predict histology with high accuracy only in the large size polyp subgroup.

Exploring Coping Strategies of Different Generations of Students Starting University.

Introduction: Coping strategies and adaptation skills are key features in successfully adjusting to university challenges. Coping skills are an essential part of the Psychological immune system, which leads to successful adaptation. Due to COVID-19 most universities have changed their face-to-face teaching for online education. Nevertheless, there is little concrete empirical evidence on how this generation of students with the ongoing impacts of disruptive changes can cope with it. Colleges and universities need to make changes in order to retain this new generation of students. Our aim was to explore the characteristics and changes in coping skills of university students from three different age groups. Method: Psychological coping skills were measured by the Psychological Immune Competence Inventory (PICI). Differences were detected between generations. Group comparisons (pre-2004, pre-Covid, and post-Covid) groups were compared) using PICI subscales using independent sample analysis of variance. The sample consisted of 4,731 university students, 2,768 (58.5%) were men and 1,730 (36.56%) were women. Results: Students from 2004 showed significantly higher scores in the Self-regulation subsystem scale compared to students in the pre-Covid and post-Covid groups. Self-regulation subsystem: F(2, 2,569.607) = 444.375, p < 0.001, η2 = 0.27: small effect, ω2 = 0.27; Resilience: F(2, 2,372.117) = 1171.855, p < 0.001, η2 = 0.14: small effect, ω2 = 0.14. Based on the results, the explained variance ratio was at least 10% based on self-regulation and resilience. Conclusions: Psychological immune capacity of students seems to decrease through the years. Nonetheless, interventions may have a further facilitating role in the maintenance and development of psychological immunity during college years.

Changes in epilepsy care during the first medical emergency period of COVID-19 pandemic in Hungary: A questionnaire survey / Az epilepsziás betegek ellátásának változása a COVID-19-járvány elso veszélyhelyzeti periódusában.

Összefoglaló. Bevezetés: A COVID-19-járvány világszerte hónapokra átalakította a járóbeteg-ellátás muködését is. Magyarországon a 2020. március 11-tol 2020. június 17-ig fennálló egészségügyi veszélyhelyzeti rendelkezések szabták meg az új kereteket. Célkituzés: Az elso veszélyhelyzeti periódus második felében, 2020. április 22. és 2020. május 5. között mértük fel az epilepsziaellátásban részt vevo orvosok véleményét, hogy milyen mértékben változott a betegek ellátása, és hogyan élték meg a változásokat személyesen. Módszer: Internetes kérdoíves véleményfelmérés történt, a Magyar Epilepszia Liga 2020. április 16-17-re tervezett, de a COVID-19-járvány miatt elhalasztott XV. kongresszusára regisztrált neurológusok között. Kilenc egyszeres vagy többszörös feleletválasztós kérdés és 'szabad kommentár' mezok álltak rendelkezésre. Eredmények: A megkeresett 116 neurológus közül 33-an válaszoltak (28%), összesen 30 kommentár került rögzítésre. 73%-uk szerint a változások komoly nehézséget okoztak, 15%-uk gondolta, hogy ennek súlyos következményei lesznek. Új betegek fogadása 53%-ban leállt, 25%-ban nagy nehézségekbe ütközött. A gondozott betegek problémáit 49%-ban a távvizit lehetoségeivel élve meg tudták oldani, de 24%-ban ez nem sikerült. A beteg távollétében lebonyolított vizitek 68%-a dokumentált telefonbeszélgetések formájában zajlott. Az orvosok kétharmada veszélyeztetve érezte magát, hogy elkapja a vírust, ebbol 40% úgy érezte, nem kap elegendo védelmet, 6% (2 fo) kapta el a fertozést. Következtetés: A COVID-19-járvány a leginkább az új szakvélemények kiadását érintette, de a gondozási feladatokat sem mindig lehetett megfeleloen megoldani. A károkat jelentosen enyhítette az ellátószemélyzet rugalmassága. A telefonvizitek, szükség esetén, az epileptológiában pótolhatják a személyes orvos-beteg találkozásokat. A járvány visszatérésének veszélye miatt a távvizit-alkalmazások technikai fejlesztése és ezek dokumentálási kérdéseinek megoldása fontos. A járványidoszakban a személyzet védelmére nagy figyelmet kell fordítani a fertozodés elkerülése és az orvosok biztonságérzetének fokozása érdekében. Orv Hetil. 2020; 161(46): 1939-1943. INTRODUCTION: COVID-19 pandemic has transformed the operation of outpatient care worldwide for months. The new framework was set in Hungary by the health emergency regulations that existed from 11. 03. 2020 to 17. 06. 2020. OBJECTIVE: In the second half of the emergency period, between 22. 04. 2020 and 05. 05. 2020, we surveyed the opinion of physicians involved in epilepsy care about the extent to which patient care had changed and how they experienced the changes in person. METHOD: An internet questionnaire survey was conducted among neurologists registered for the annual congress of the Hungarian Chapter of the International League Against Epilepsy. Nine single- or multiple-choice questions and 'free comment' fields were available. RESULTS: Of 116 neurologists contacted, 33 responded (28%), and a total of 30 comments were recorded. 73% said the changes caused a serious difficulty, 15% thought it would have serious consequences. Reception of new patients was stopped in 53%, and 25% encountered great difficulties. In 49%, the problems of the cared patients could be solved using remote visits, but 24% could not solve them properly. 68% of outpatient visits took the form of documented telephone conversations. Two-thirds of doctors feared catching the virus, 40% of whom felt they were not getting enough protection. 6% caught the infection. CONCLUSION: The COVID-19 pandemic has mostly affected the issuance of new expert opinions, but care tasks have not always been adequately addressed. The damage was significantly mitigated by the flexibility of the care staff. Telephone visits, if necessary, can replace personal doctor-patient encounters in epileptology. The technical development of remote visit applications and their documentation issues are important. During the pandemic period, great care must be taken to protect staff in order to avoid infection and increase the sense of safety of doctors. Orv Hetil. 2020; 161(46): 1939-1943.

ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.

Fatty acids and glucose are the main bioenergetic substrates in mammals. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data showed that Adck2+/- mice exhibited impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in Coenzyme Q (CoQ) biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

Regulation of influenza A virus mRNA splicing by CLK1.

Influenza A virus carries eight negative single-stranded RNAs and uses spliced mRNAs to increase the number of proteins produced from them. Several genome-wide screens for essential host factors for influenza A virus replication revealed a necessity for splicing and splicing-related factors, including Cdc-like kinase 1 (CLK1). This CLK family kinase plays a role in alternative splicing regulation through phosphorylation of serine-arginine rich (SR) proteins. To examine the influence that modulation of splicing regulation has on influenza infection, we analyzed the effect of CLK1 knockdown and inhibition. CLK1 knockdown in A549 cells reduced influenza A/WSN/33 virus replication and increased the level of splicing of segment 7, which encodes the viral M1 and M2 proteins. CLK1-/- mice infected with influenza A/England/195/2009 (H1N1pdm09) virus supported lower levels of virus replication than wild-type mice. Screening of newly developed CLK inhibitors revealed several compounds that have an effect on the level of splicing of influenza A gene segment M in different models and decrease influenza A/WSN/33 virus replication in A549 cells. The promising inhibitor KH-CB19, an indole-based enaminonitrile with unique binding mode for CLK1, and its even more selective analogue NIH39 showed high specificity towards CLK1 and had a similar effect on influenza mRNA splicing regulation. Taken together, our findings indicate that targeting host factors that regulate splicing of influenza mRNAs may represent a novel therapeutic approach.

[Complex supportive care of patients with breast cancer. The preliminary results of a psychological intervention study]. / Emlodaganatos nobetegek komplex támogató terápiája. Egy pszichológiai intervenciós kutatás elozetes eredményei.

Introduction: Interdisciplinary studies confirm that the traumatic nature of cancer diagnosis and the long course of treatment may often lead to a series of emotional problems among cancer patients, this way precluding physical and psychological recovery. Aim: The aim of the study was to create a complex psychosocial intervention program for breast cancer patients and to present our preliminary results. Method: In our 6 week long study, 50 breast cancer patients were assessed. The intervention group comprised of 20 patients, the control group comprised of 30 patients. Measurements included the Beck Depression Inventory (BDI), the Spielberger State and Trait Anxiety Inventory (STAI), the Surgical Fear Questionnaire (SFQ), the Visual Analogue Scale (VAS), the Functional Assessment of Cancer Therapy - Breast (FACT-B) and the Breast-Impact of Treatment Scale (BITS). Therapeutic tools used were the PRISM-D and the Body-Sculpture Test. Results: Our results indicate that the psychological interventions may have an instant stress-relieving and calming effect on our patients, this way providing social support. The type of surgery significantly influenced the levels of body change stress. Conclusion: Our results highlight the importance of early psychological screening among breast cancer patients before and after surgery as well. Orv Hetil. 2019; 160(18): 700-709.

Synthesis and characterization of amino acid substituted sunitinib analogues for the treatment of AML.

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Sunitinib, a multikinase inhibitor, was the first Fms-like tyrosine kinase 3 (FLT3) inhibitor clinically used against AML. Off-target effects are a major concern for multikinase inhibitors. As targeted delivery may reduce such undesired side effects, our goal was to develop novel amino acid substituted derivatives of sunitinib which are potent candidates to be used conjugated with antibodies and peptides. In the current paper we present the synthesis, physicochemical and in vitro characterization of sixty two Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutant kinase inhibitors, bearing amino acid moieties, fit to be conjugated with peptide-based delivery systems via their carboxyl group. We determined the solubility, pKa, CHI and LogP values of the compounds along with their inhibition potential against FLT3-ITD mutant kinase and on MV4-11 cell line. The ester derivatives of the compounds inhibit the growth of the MV4-11 leukemia cell line at submicromolar concentration.

Spatial characterization of light beams analyzed by cylindrical-grating slit-less spectrometers.

In this work, we theoretically analyze the spatial information provided by cylindrical-grating slit-less spectrometers. We raise attention on the often not considered property that the spatial features acquired using these spectrometers are different from what can be obtained using a spectrometer with an entrance slit. In relation to this, we also highlight that they do not provide information directly on the real spatial beam profile. It is important to consider this fact in spatio-spectral analysis of extreme ultraviolet radiation, often carried out using cylindrical-grating slit-less spectrometers. Since the models used are based on the Fresnel diffraction integral and ideal optical systems, the results are valid also for other spectral regions.

Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma.

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).

What contributes to long-term quality of life in breast cancer patients who are undergoing surgery? Results of a multidimensional study.

PURPOSE: This study aims to examine the key determinants of long-term quality of life in breast cancer patients who are undergoing surgery using a multidimensional approach and taking into account preoperative and post-operative psychological characteristics such as anxiety, depression, posttraumatic growth, body image, and physical activity as well as medical parameters. METHODS: The study involved 63 breast cancer patients from the Department of Surgery at the University of Szeged. Assessments occurred 1 day before surgery as well as 3 days and 18 months after surgery using the Spielberger State and Trait Anxiety Inventory (STAI), Beck's Depression Inventory (BDI), Functional Assessment of Cancer Therapy-Breast Cancer Scale (FACT-B), Posttraumatic Growth Inventory (PTGI) and Breast Impact of Treatment Scale (BITS). Data relating to physical activity, medical parameters and sociodemographic characteristics were also collected. RESULTS: The level of depression did not change over time. State anxiety decreased 18 months after the surgery compared to before the surgery; however, there was a greater decrease immediately after the surgery and then anxiety increased again 18 months later. Trait anxiety was associated with quality of life, posttraumatic growth and body image. Posttraumatic growth and the level of depression were found to be possible contributing factors to the increase in long-term quality of life. CONCLUSIONS: The results show that the timely detection and proper management of psychological distress and the enhancement of posttraumatic growth are of great value, as they might be important contributing factors to long-term quality of life in breast cancer patients.