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BackgroundThe BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.Patients and methodsBOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.ResultsAt the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95% CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.ConclusionsIn BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P < 0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.Trial registration numberNCT00863655.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655.

The procedure of the T-2 and НT-2 toxins determination in wheat grain was developed by high performance liquid chromatography according to the following criteria: specificity, linearity, limits of detection (LOD), limits of quantification (LOQ), trueness (recovery), precision, stability. It was found that the correlation coefficient (R²) for T-2 and HT-2 toxin was 0.9999. Mean recoveries from (R, %) for T-2 and HT-2 toxin at the level of 50-150 μg·kg-1 from wheat (sample blank) were 91 and 87 %, respectively. The relative standard deviation (RSD, %) of the measurement results under conditions of repeatability and intra-laboratory precision ranged from 0.23 to 3.93 %. The limits of quantification of the method for T-2 and HT-2 toxin was 2.2 and 1.2 μg·kg-1, respectively. These data are within the range of acceptable minimum levels in accordance with Commission Regulation (EC) No 401/2006. It is confirmed that the standards of T-2, HT2 toxins in solutions can be stored up to 7 days in a freezing chamber, a refrigerator and at room temperature in a tightly closed container without actual loss of concentration. It was found that T-2 and НT-2 in a solution cannot be stored in a lit place, because according to the data obtained, sunlight leads to the destruction of these mycotoxins by 52 % and 59 %, respectively. [ABSTRACT FROM AUTHOR]

Abstract Background Primary neuroendocrine carcinomas (NECs) are very rare entities accounting for 0.49% of all malignancies. Within the head and neck, the most common sites are the larynx and paranasal sinuses, while the hypopharynx is seldom described. Case We present a patient with a poorly differentiated metastatic NEC of the hypopharynx treated palliatively with organ‐preserving surgery and post‐operative chemotherapy, and literature review for well‐documented pure hypopharyngeal NECs. Our patient died of chest infection during chemotherapy, 4 months after surgery. Conclusion Chemotherapy remains the mainstay of treatment in the presence of metastases with 2‐year overall survival of 15.7%. Due to the aggressive nature of poorly differentiated metastatic NECs, surgical management is seldom considered. We report and advocate the successful palliative role of organ‐preserving, minimally invasive trans‐oral LASER micro‐surgery and neck dissection to control loco‐regional head and neck disease, safe‐guarding better quality of home life, despite limited life expectancy for this condition.

Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in Drosophila neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes. We hypothesize that individual neuronal subtypes respond differently to IIS changes, thus the behavioral outcomes of pan-neuronal IIS reduction are the balance of positive, negative and neutral functional effects. In order to further understand how reduced IIS in neurons independently modulates lifespan and locomotor behavioral senescence we expressed a dominant negative Insulin receptor transgene selectively in individual neuronal subtypes and measured the effects on lifespan and two measures of locomotor senescence, negative geotaxis and exploratory walking. IIS reduction in cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons was found to have either no affect or a detrimental effect on lifespan and locomotor senescence. However, reduction of IIS selectively in serotonergic neurons resulted in extension of lifespan in females with no effect on locomotor senescence. These data indicate that individual neuronal subtypes respond differently to IIS changes in the modulation of lifespan and locomotor senescence, and identify a specific role for the insulin receptor in serotonergic neurons in the modulation of lifespan.

Chemicals of the macrolide group - Pharmazin® and Tilotsiklinvet® - are widely used in veterinary practice in poultry farming for treatment or prevention in Ukraine. We have conducted a study on the pharmazin and tilotsiklinvet influence on the weight of broiler chickens before a slaughter; the weight of semi-dressed and dressed carcasses and internal organs of broiler chickens; the slaughter yield of broiler chicken carcasses and the ratio of their internal organs to a slaughter yield. Four groups of broiler chickens of the Cobb 500-day-old cross-breed were formed: two controls and two experimental (12 broiler chickens each). Chickens of the first experimental group were fed with pharmazin containing the active substance (AS) tylozine tartrate 500 mg per 1 g, and the second - with a tilotsiklinvet containing the (AS) tylozine tartrate and doxycycline glycate of 100 mg per 1 g of powder. Pharmazin and tilotsiklinvet were fed orally with a water at a dose of 1 g per 1 dm3 of water according to the instructions for their use. These antibiotics were fed to broiler chickens with preventive purpose for the first 3 days of life, 28−29 and 38−42 days of the experiment. At the end of the antibiotics feeding, 6 broiler chickens from each group were slaughtered at the beginning of the elimination period (after 3 hours) and after the end of the withdrawal period (after 5−8 days), respectively, after the last pharmazin and tilotsiklinvet usage. It has been established that the use of pharmazin and tilotsiklinvet positively affects the productivity of chicken broilers. As a result, one can observe a significant increase in weight of broiler chickens before a slaughter (р≤0,001, р≤0,01). Slaughter yield increased by 8,2% when feeding pharmazin, and tilotsiklinvet - by 4,3%. Also, the weight of all the edible internal organs increased when using pharmazin and tilotsiklinvet (p≤0,05) and the weight of the liver and muscular part of the stomach when using tilotsiklinvet (p≤0,05). [ABSTRACT FROM AUTHOR]

The territory of Ukraine is unique area in terms of iodine, which indicates the need for daily additional consumption of iodine along with the foodstuff. The major products applied for iodine deficiency prevention include salt and water optimized in terms of iodine and another microelements content. The thesis objective is to study influence of Iodis-Concentrate® preparation on rabbit meat quality parameters. Our aim was to find out the amino acid composition, the fatty-acid composition and mineral composition, as well as the iodine content in rabbit meat. There were two groups of two months old laboratory rabbits formed: the stud and control group (5 rabbits in each group). The rabbits of the control group were watered with the water taken from the well located in Obukhiv, Kyiv Oblast, while the rabbits of the study group were watered with the same water, although adding Iodis-Concentrate Preparation in the dosage of 0.35 mg/kg. In terms of organoleptic, physical and chemical indices, the rabbit meat corresponded to the fresh meat. The amino acid composition of the rabbit meat in the study and control group was slightly different. Subject to watering the rabbits with potable water with Iodis-Concentrate preparation added, the contents of certain indispensable and dispensable amino acids, and the aggregate contents thereof slightly increased, however, no trustworthy difference was recorded. No abnormal ratio of indispensable and dispensable amino acids was recorded. The biological value of the rabbit meat is preserved. As regards the fatty acids content, the meat of rabbits treated with Iodis- Concentrate preparation contained more fatty acids, as follows: lauric acid, myristic acid, Cys-10 heptadecenoic acid, elaidic acid, oleine acid, linolic acid, linolenic acid, Cys-11- eicosenic acid, Cys-8, 11,14- eicosatrienoic acid, Eicosatetraenoic acid, as compared to the control parameters, which indicates stimulation of lipid metabolism. During studying the influence of Iodis- Concentrate preparation on rabbit meat composition, the trustworthy high contents of the following microelements and microelements was ascertained: aluminum, calcium, chrome, ferrum, magnesium, manganese, natrium, strontium, and zinc. In the meat of rabbits treated with Iodis-Concentrate preparation, the researcher unveiled twice higher contents of iodine as compared to the performance in the control group of rabbits. [ABSTRACT FROM AUTHOR]