Number Of Unfavorable Factors Research Articles

Third Generation ALK Inhibitors - The Development of Lorlatinib and the Problems that Exist

The malignant tumor with the greatest morbidity and fatality rates in the world today is lung cancer, from which Non-Small Cell Lung Cancer (NSCLC) accounts for 85%. To treat NSCLC, a variety of targeted therapeutics been developed in medicine. ALK inhibitors are one of them, and they're frequently used to treat NSCLC.The 3rd Generation of ALK inhibitors are now in use, starting with the initial 1st generation ALK inhibitors. Because the development of 1st and 2nd generation ALK inhibitors medicines has been motivated by a number of unfavorable factors. These medications include the 3rd generation ALK inhibitor lorlatinib as well as the 2nd and 3rd generation ALK inhibitors ceritinib and alectinib. Current study discusses the clinical features, effectiveness, and side effects of lorlatinib as well as its pharmacological effects.

Estimation results of the spring bread wheat varieties on disease resistance in the Kazan Research Center

In the Republic of Tatarstan, due to favorable soil-climatic and market conditions, spring wheat production is developed, but wheat grain yields are limited by a number of unfavorable factors, one of which is a spread of fungal diseases. At the same time, the pressure of pathogenic fungi makes it possible to carry out fruitful breeding work in Tatarstan on resistance to diseases, which is on of the main activity of the Kazan Research Center of the RAS. The purpose of the current study was to estimate ten new varieties for resistance to major fungal diseases. The study on resistance to leafy diseases, such as powdery mildew, stem rust, brown leaf rust, dark brown leaf blotch was carried out at a natural infectious background, to kernel smut on an artificial infectious background inoculating seeds with spores of kernel smut. The study was carried out between the years of 2017 and 2021. The analysis for the possible presence of stem rust resistance genes was performed by a PCR analysis. As a result of the study, there was found out that the varieties ‘Sto let TASSR’, ‘Balkysh’, ‘Khazine’, ‘Chistopolskaya’, ‘Bulyak’ had a complex resistance to all studied diseases. The variety ‘Sitara’ had a strong field resistance to powdery mildew and kernel smut. The variety ‘Barakat’ had a strong field resistance to powdery mildew and leaf rust. The variety ‘Nadira’ was moderately resistant to powdery mildew and dark brown leaf spot. The varieties ‘Ekada 265’ and ‘Ekada 282’ were highly resistant to local stem rust populations. The molecular genetic estimation of the stem rust resistant varieties of spring bread wheat ‘Chistopolskaya’, ‘Sto let TASSR’, ‘Balkysh’, ‘Ekada 282’ for the identification of effective Sr-genes has shown that their resistance is apparently regulated by the Sr31 gene.

Les traitements par ARN interférents et par oligonucléotides antisens actuellement disponibles en France : une mise au point

L’arrivée des vaccins anti Covid-19 à ARN en 2020 ne doit pas occulter le fait que nous disposons déjà depuis plusieurs années de traitements à base d’ARN interférents ou d’oligonucléotides antisens dans un certain nombre de maladies rares de pronostic très sombre telles que l’amylose à transthyrétine, la porphyrie hépatique aiguë, l’hyperoxalurie primitive, l’amyotrophie spinale ou l’hyperchylomicronémie familiale. Si leurs performances, à l’inverse de celles des vaccins, ne sont pour l’instant qualifiées que de progrès thérapeutiques modérés dans les stratégies thérapeutiques opposées à ces maladies, il y a lieu de tenir compte du fait que leur évaluation initiale a été pénalisée par un certain nombre de facteurs défavorables : des essais de petits effectifs, des modalités thérapeutiques à affiner, le manque de recul, sur leurs effets à long terme mais surtout le choix du moment de l’instauration du traitement dans l’évolution naturelle de la maladie. Ce choix n’est pas anodin car l’on imagine mal que les produits utilisés puissent, au-delà d’une simple stabilisation de la maladie installée, permettre sa régression dès lors que certaines lésions constituées sont irréversibles. C’est pourquoi leur mise en œuvre très précoce, éventuellement fondée sur un dépistage génétique, est une piste à saisir dans l’intérêt des patients. Mais, dans le contexte concurrentiel des innovations dans le domaine, ARN interférents et oligonucléotides antisens devront compter avec les thérapies géniques et l’édition du génome par la technique CRISPR-Cas 9.

Experience of using 1<sup>st</sup> line combination immunotherapy in patients with metastatic renal cell carcinoma

The study objective is to evaluate effectiveness and tolerability of 1st line combination immuno-oncological therapy with nivolumab and ipilimumab in patients with metastatic renal cell carcinoma (mRCC) in clinical practice.Materials and methods. The study included 38 patients with mRCC who received combination immunotherapy between July of 2019 and September of 2021. Median follow-up duration was 8 (2-25) months. Mean age of the patients was 58.3 (20-85) years. Previously 22 (57.9 %) patients underwent surgical treatment. Unfavorable physical status 2-3 per the ECOG scale was observed in 10 (26.3 %) patients. Clear-cell type of renal cell carcinoma was diagnosed in 34 (89.6 %) patients, non-clear-cell types in 4 (10.4 %). Sarcomatoid component in the tumor was detected in 8 (21.0 %) patients. G3-4 mRCC variant was verified in 16 (42.1 %) patients. Poor prognosis per the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) scale was identified in 16 (42.1 %) patients, intermediate -in 20 (52.6 %) patients. All 4 administrations of combination immunotherapy were received by 29 (76.3 %) patients.Results. For median follow-up duration of 8 (2-25) months, 23 (60.5 %) patients continue treatment, 15 (39.5 %) completed therapy with nivolumab and ipilimumab due to various reasons including progression in 11 (28.9 %), death in 2 (5.3 %), intolerable toxicity in 2 (5.3 %) cases. Median duration of combination immunotherapy was 9 (2-24) months. Subsequent antitumor therapy was administered to 3 (7.9 %) patients. During induction course immune-mediated adverse event (grade III-IV hepatitis) developed in 3 (7.9 %) patients. Adverse events were observed in 81.6 % of patients, including grade III-IV in 23.7 % of patients. Objective response was observed in 44.8 % of cases, complete response in 5.3 % of cases, partial response in 39.5 % of cases; controlled disease was achieved in 84.3 % of patients. Median progression-free survival and overall survival were 8 months.Conclusion. In our study despite large number of patients with poor prognosis and poorly differentiated tumors, 64.0 % of patients are alive and 60.5 % of patients continue treatment without disease progression after 18 months of combination immunotherapy. Progression-free survival was significantly affected by sarcomatoid component in the tumor, number of unfavorable factors per the IMDC scale, best response per RECIST 1.1; overall survival was significantly affected by sarcomatoid component in the tumor, sum of measurable lesions, number of unfavorable factors per the IMDC scale, best response per RECIST 1.1, and presence of symptomatic metastases in the brain.

Analysis of a Feasibility Study of a Precision Grinding Process for Industrial Blades Used in the Cutting of Soft Tissues by a Prototype 5-Axis CNC Grinding Machine

Obtaining a high quality product (filet) is often necessary to effectively separate the soft tissues of fish raw material. An intensive technological process and a number of unfavorable factors can generate the wear of low-stiffness planar industrial cutting blades used for this purpose. The relatively short time of efficient work of the blade causes the production stoppages needed for its exchange, which consequently can inflict significant financial losses. The wear of industrial cutting blades is one of the important and still unsatisfactorily solved problems occurring in the fish and seafood industry, especially in its branches related to fish processing. In this paper, the authors propose an original solution of the above problem by the possibility of renewing the cutting ability of industrial cutting blades by the process of precise grinding realized on the prototype 5-axis CNC (Computerized Numerical Control) grinding machine. The detailed description of a newly designed and constructed technological machine was expanded by the results of tests carried out in industrial conditions. Results of the regeneration of blades at variable parameters of the grinding process (vw = 300–700 mm/min, ns = 38,000 min−1) were analyzed on the basis of surface texture measurements by Talysurf CLI 2000 optical profilometer. The surface texture parameter (amplitude, spatial, and hybrid) analysis allowed to determine the most favorable machining parameters for which compatibility of cutting edge geometry was obtained. The proposed solution can be an interesting alternative to other ways of renewing/exchanging industrial cutting blades.

СОВРЕМЕННЫЙ ПОДХОД К ФУНКЦИОНАЛЬНОМУ ПИТАНИЮ ДЕТЕЙ ПЕРВОГО ГОДА ЖИЗНИ.

<p>У статті розглядаються<br />аспекти функціонального харчування дітей раннього віку з метою профілактики та лікування дисбіозів кишечника.<br />Серед значної кількості несприятливих факторів, які впливають на здоров'я дитини, особливе місце займає<br />нераціональне харчування. Порушення в організації вигодовування дітей першого року життя є однією з провідних<br />причин поширеності аліментарнозалежних захворювань. Оптимальним продуктом харчування для дітей перших<br />місяців життя є материнське молоко, яке відповідає особливостям дитячої травної системи та обміну речовин,<br />забезпечує адекватний розвиток дитячого організму при раціональному харчуванні матері-годувальниці. На<br />даний час поширеність і тривалість грудного вигодовування не настільки високі, діти часто переводяться на<br />штучне та частково грудне вигодовування. Це створює передумови для формування порушень мікробіоценозу<br />кишечника за умов використання неадаптованих молочних сумішей. Одним із можливих шляхів вирішення<br />проблеми дисбіозів у дітей раннього віку є використання високоадаптованих молочних сумішей, збагачених<br />пребіотиками. Додаткове введення пребіотиків до складу молочних сумішей дозволяє відтворити дію<br />олігосахаридів грудного молока, нормалізувати склад мікрофлори кишечника та оптимізувати процеси травлення.</p>

Occupational health issues and ways to improve health care for road transport workers

During the hygienic assessment of the working conditions of workers performing repair and maintenance of cars, the influence of a number of unfavorable factors of the working environment was noted: intense physical labor during the main locksmith and mechanical work, gas pollution of the air with exhaust gases of automobile engines, tetraethyl lead vapors during engine repair, low air temperatures in transitional And the cold periods of the year, etc. [1-3].