Biomarkers in Thyroid Tumor Research: New Diagnostic Tools and Potential Targets of Molecular-Based Therapy

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Планування ЗЕД на підприємствах малого та середнього бізнесу

Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) display a highly diverse genetic background and recent gene expression profiling studies have shown that PCC and PGL (together PPGL) alter either kinase signaling pathways or the pseudo-hypoxia response pathway dependent of the genetic composition. Recurrent mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been verified in sporadic PPGLs. In order to further establish the HRAS mutation frequency and to characterize the associated expression profiles of HRAS mutated tumors, 156 PPGLs for exon 2 and 3 hotspot mutations in the HRAS gene was screened, and compared with microarray-based gene expression profiles for 93 of the cases. The activating HRAS mutations G13R, Q61R, and Q61K were found in 10/142 PCC (7.0%) and a Q61L mutation was revealed in 1/14 PGL (7.1%). All HRAS mutated cases included in the mRNA expression profiling grouped in Cluster 2, and 21 transcripts were identified as altered when comparing the mutated tumors with 91 HRAS wild-type PPGL. Somatic HRAS mutations were not revealed in cases with known PPGL susceptibility gene mutations and all HRAS mutated cases were benign. The HRAS mutation prevalence of all PPGL published up to date is 5.2% (49/950), and 8.8% (48/548) among cases without a known PPGL susceptibility gene mutation. The findings support a role of HRAS mutations as a somatic driver event in benign PPGL without other known susceptibility gene mutations. HRAS mutated PPGL cluster together with NF1- and RET-mutated tumors associated with activation of kinase-signaling pathways.Funding Agencies|Swedish Cancer Foundation; StratCan; Swedish Research Council; Cancer Research Foundations of Radiumhemmet; Karolinska Institutet; Stockholm County Council</p

Реконструкция системы электроснабжения ОАО «СтанкоГомель» в связи с изменением технологического процесса и разработкой энергосберегающих мероприятий

The aim of the present study was to compare an ultrasonically activated instrument (US), monopolar electrosurgery, and bipolar electrosurgery (ES) with respect to heat production, nerve function, and nerve morphology following in vivo application. less thanbrgreater than less thanbrgreater thanThe biceps femoris muscle of anesthetized rats was cut in a standardized manner longitudinally 1 mm adjacent to the sciatic nerve using US shears, a monopolar ES knife, or a bipolar ES scissors. Activation time and temperature were recorded continuously within 1-4 mm of the activation site ipsilateral and contralateral to the nerve with two thermoelectric microsensors. Temperature rise and time delay of reaching the temperature maximum, as an expression of heat spread within tissue, maximum temperature, and thermal dose (equivalent time of exposure at 43A degrees C) were measured and calculated. A total of 49 functional experiments were conducted. The electromyographic (EMG) potential was recorded distally. Nerve dysfunction was defined as more than 10% loss of the evoked EMG amplitude. Forty-eight nerves were coded and submitted to blind histopathological examination, and morphological damage was graded on a 4-grade scale. less thanbrgreater than less thanbrgreater thanThe maximum temperature elevation and the thermal dose were significantly higher for the bipolar ES compared with the US instrument ( = 0.024, = 0.049), and with much less variation of results for the US instrument. The monopolar ES maximum temperature and thermal dose were lower, but a very large variation occurred, probably as a result of more random electrical spread to the ground electrode and muscle motion artifacts. Functional loss was least common in the US group-without being significant-compared to bipolar and monopolar ES. Moderate and severe morphological damage was significantly less common in the US group than in the monopolar ES group ( = 0.041). We found no statistically significant correlation between the highest temperatures and the degree of morphological damage or functional loss less thanbrgreater than less thanbrgreater thanThe temperature elevation depends strongly on the distance to the activated instrument. The bipolar ES scissors generates a higher maximum temperature and thermal dose with a greater variation in than the US. Functional loss and severe morphological damage were uncommon in all groups.Funding Agencies|FORSS|

Розвиток духовності особистості в процесі фахової підготовки майбутніх учителів образотворчого мистецтва

(uk) У статті наголошується, що вчитель образотворчого мистецтва виступає носієм не лише спеціальних знань та умінь, але і носієм духовних цінностей. Духовне збагачення і вдосконалення кожної особистості відбувається протягом всього життя в тому числі і в процесі навчання. Гуманізація освіти та естетичне виховання спрямовано на формування гармонійної цілісної особистості, загальнокультурний її розвиток. Засобами естетичного виховання в мистецтві виступає художній образ. Художній образ є відображенням дійсності яке містить в собі не лише суб’єктивний досвід автора, його розуміння та відношення до об’єктів дійсності, але і відбитки культурно-історичного досвіду, естетичних цінностей, але і відбитки культурно-історичного досвіду, естетичних цінностей соціуму загалом. На їх базі і формується всебічно та гармонійно розвинута особистість із вищими моральними цінностями, естетичними канонами та ідеалами.(ru) В статье делается акцент на то, что учитель изобразительного искусства выступает носителем не только специальных знаний и умений, но и носителем духовных ценностей. Духовное обогащение и совершенствование каждой личности происходит на протяжении всей жизни в том числе и в процессе обучения. Гуманизация образования и эстетическое воспитание направлены на формирование гармоничной целостной личности и ее общекультурное развитие. Средством эстетического воспитания в искусстве выступает художественный образ. Художественный образ является отражением действительности, которое содержит в себе не только субъективный опыт автора, его понимание и отношение к объектам действительности, но и отпечатки культурно-исторического опыта, эстетических ценностей социума в целом. На их базе и формируется всесторонне и гармонично развитая личность с высокими моральными ценностями, эстетическими канонами и идеалами.(en) Importance of education in society is determined by the need to raise the national consciousness of the saved and nurturing genuine citizen. Spiritual enrichment and improvement of each individual occurs throughout life including during training. Spirituality determines the direction of all mental, emotional, sensual, strong-willed human qualities and its ability to self yourself as a person. Master of Fine Arts acting carrier not only specialized knowledge and skills, but also a bearer of spiritual values. Humanizing education and aesthetic education aims at forming a harmonious whole person, her general cultural development. Art is an integral part of spiritual culture, a reflection of the artistic representations of the human form of the world of reality. The means of aesthetic education in the art of acting artistic image. Artistic image is a reflection of reality, which contains not only the subjective experience of the author, and understanding related to the objects of reality, but the prints are of cultural and historical experience, the aesthetic values of society as a whole. At their base is formed fully and harmoniously developed personality with higher moral values, aesthetic canons and ideals

65 YEARS OF THE DOUBLE HELIX Genetics informs precision practice in the diagnosis and management of pheochromocytoma

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.Peer reviewe

Демографический потенциал Республики Беларусь

Материалы III Междунар. науч. конф. студентов, аспирантов и молодых ученых, Гомель, 20 мая 2010 г

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

Nuclear and mitochondrial DNA alterations in pheochromocytomas and paragangliomas, and their potential treatment

Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is little information about its involvement in pheochromocytomas and paragangliomas (PCCs/PGLs) formation. PCCs and PGLs are rare endocrine tumors of the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia that can synthesize and secrete catecholamines. Over the last 3 decades, the genetic background of about 60% of PCCs/PGLs involving nuclear DNA alterations has been determined. Recently, a study showed that mitochondrial alterations can be found in around 17% of the remaining PCCs/PGLs. In this review, we summarize recent knowledge regarding both nuclear and mitochondrial alterations and their involvement in PCCs/PGLs. We also provide brief insights into the genetics and the molecular pathways associated with PCCs/PGLs and potential therapeutical targets

Training in endocrine surgery

Background/purpose In Europe, the Division of Endocrine Surgery (DES) determines the number of operations (thyroid, neck dissection, parathyroids, adrenals, neuroendocrine tumors of the gastro-entero-pancreatic tract (GEP-NETs)) to be required for the European Board of Surgery Qualification in (neck) endocrine surgery. However, it is the national surgical boards that determine how surgical training is delivered in their respective countries. There is a lack of knowledge on the current situation concerning the training of surgical residents and fellows with regard to (neck) endocrine surgery in Europe. Methods A survey was sent out to all 28 current national delegates of the DES. One questionnaire was addressing the training of surgical residents while the other was addressing the training of fellows in endocrine surgery. Particular focus was put on the numbers of operations considered appropriate. Results For most of the operations, the overall number as defined by national surgical boards matched quite well the views of the national delegates even though differences exist between countries. In addition, the current numbers required for the EBSQ exam are well within this range for thyroid and parathyroid procedures but below for neck dissections as well as operations on the adrenals and GEP-NETs. Conclusions Training in endocrine surgery should be performed in units that perform a minimum of 100 thyroid, 50 parathyroid, 15 adrenal, and/or 10 GEP-NET operations yearly. Fellows should be expected to have been the performing surgeon of a minimum of 50 thyroid operations, 10 (central or lateral) lymph node dissections, 15 parathyroid, 5 adrenal, and 5 GEP-NET operations.Funding Agencies|Linkoping University</p

http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-78807 Super-selective Venous Sampling in Conjunction with QuickPTH for Patients with Persistent Primary Hyperparathyroidism: Report of Five Cases Running title: Super-selective Venous Sampling in pHPT

Super-selective venous sampling in conjunction with quickPTH for patients with persistent primary hyperparathyroidism: report of five case