Effect of cycling specialization on effort and physiological responses to uphill and flat cycling at similar intensity

[EN] Power output is considered one of the best tools to control external loads in cycling, but the relationship between a target power output and the physiological responses may suffer from the effects of road gradient, which is also affected by cyclist specialization. The objective was to determine the effects of cyclist specialization on effort perception and physiological response (heart rate and lactate concentration) while sustaining efforts at similar power output but riding on two different road gradients. Nineteen male competitive road cyclists performed two randomized trials of 10 min at 0% (velodrome) and 10 min at 6% road gradient (field uphill), at an intensity of 10% ± 3% below the individual’s functional threshold power. Cadence was kept between 75 and 80 rpm in both trials and posture remained unchanged during the tests. Heart rate, speed, cadence, power output, blood lactate, and rate of perceived effort were measured for each trial. K-means cluster analyses differentiate uphill (n = 10) and flat specialists (n = 9) according to lactate responses. Flat specialists presented lower heart rate (p < 0.001 and ES = 0.2), perceived exertion (p < 0.01 and ES = 0.7), and blood lactate concentration (p < 0.001 and ES = 0.7) riding on the flat than uphill. Uphill specialists presented lower perceived exertion (p < 0.01 and ES = 0.8) and blood lactate concentration (p < 0.01 and ES = 0.5) riding uphill than on the flat. In conclusion, the combination of cyclist specialization and road gradient affects physiological and effort perception parameters in response to a similar power output demand. These factors deserve attention in training schedules and monitoring performance using power output data.S

Analysis of results of effective dose estimation obtained from RADAR 2017 dose assessment model for nuclear medicine procedures

EP-296 Aim/Introduction: To analyze the results of effective dose (E) estimation of the most frequent procedures using photon emitters in Nuclear Medicine, obtained from RADAR 2017 dose assessment model. To compare these results with those obtained from ICRP 128 (2015) recommendations, and to assess how using each dose assessment model can change E results. Materials and Methods: E estimation data was collected from photon emitter procedures performed during the last year in our department, obtained from RADAR 2017 dose estimation model for age groups: = 1 year old; >1-5 years old ; >5- 10 years old, >10- 15 years old and adults. Injected activity was the one recommended by international guidelines and EANM Pediatric and Dosimetry Committees. Hybrid exams (SPECT / CT) and procedures for which there is no RADAR 2017 dosimetry estimation were excluded. Results for (E) were compared with those obtained by using ICRP 128 (2015) recommendations. Results: With RADAR 2017 dose evaluation model we obtained a lower mean value of E on most of the procedures that were analyzed, being significantly lower for Renogram, Renal scintigraphy on >10-15 years old, Thyroid scintigraphy, Meckel’s scan and Bone Scan (0.12 to 1.16 mSv, 25% to 67%). Brain perfusion and Renal scintigraphy on ages under 10 obtained a significantly greater difference for E (0.33 to 2.85 mSv, 26% to 29%). Conclusion: These results are an updated collection of estimated E values for photon-emitting radiopharmaceuticals commonly used in Nuclear Medicine, considering RADAR 2017 dose assessment model compared to ICRP 128) recommendations. Methodological changes on estimation lead to lower E for most of diagnostic procedures using photon emitters, this is of special interest for patients undergoing repeated ionizing radiation (dosimetry history)

Why Were More Than 200 Subjects Required to Demonstrate the Bioequivalence of a New Formulation of Levothyroxine with an Old One?

At the request of French Regulatory Authorities, a new formulation of Levothyrox® was licensed in France in 2017, with the objective of avoiding the stability deficiencies of an existing licensed formulation. Before launching the new formulation, an average bioequivalence (ABE) trial was conducted, having enrolled 204 subjects and selected for interpretation a narrow a priori bioequivalence range of 0.90–1.11. Bioequivalence was concluded. In a previous publication, we questioned the ability of an ABE trial to guarantee the switchability within patients of the new and old levothyroxine formulations. It was suggested that the two formulations should be compared using the conceptual framework of individual bioequivalence. The present paper is a response to those claiming that, despite the fact that ABE analysis does not formally address the switchability of the two formulations, future patients will nevertheless be fully protected. The basis for this claim is that the ABE study was established in a large trial and analyzed using a stringent a priori acceptance interval of equivalence. These claims are questionable, because the use of a very large number of subjects nullifies the implicit precautionary intention of the European guideline when, for a Narrow Therapeutic Index drug, it recommends shortening the a priori acceptance interval from 0.80–1.25 to 0.90–1.11

Interaction of high energy protons in nuclear emulsions loaded with b 10 and LiF

An experiment is proposed to expose nuclear emulsions loaded with B{sup 10} and LiF to high energy protons at 100 GeV, 150 GeV and 200 GeV. The purposes are: (i) to measure the total cross-sections at these incident energies, (ii) to investigate charged multiplicity as a function of energy, (iii) to investigate the angular distribution and development of hadron showers in collisions of protons with nuclei

A phase II irinotecan–cisplatin combination in advanced pancreatic cancer

We report a cisplatin and irinotecan combination in patients with biopsy-proven advanced pancreatic adenocarcinoma. Patients were selected from a specialist centre and required good performance status (KPS&gt;70%), measurable disease on CT scan, and biochemical and haematological parameters within normal limits. Based on a two-stage phase II design, we aimed to treat 22 patients initially. The study was stopped because of the death of the 19th patient during the first treatment cycle, with neutropenic sepsis and multiorgan failure. A total of 89 treatments were administered to 17 patients. Serious grade 3/4 toxicities were haematological (neutropenia) 6%, diarrhoea 6%, nausea 7% and vomiting 6%. Using the clinical benefit response (CBR) criteria, no patients had an overall CBR. For responses confirmed by CT examination, there was one partial response (5%), three stable diseases lasting greater than 6 weeks (16%), with an overall 22% with disease control (PR+SD). The median progression-free and overall survival was 3.1 months (95% CI: 1.3-3.7) and 5.0 (95% CI: 3.9-10.1) months, respectively. Although this synergistic combination has improved the response rates and survival of other solid tumours, we recommend caution when using this combination in the palliation of advanced pancreatic cancer, because of unexpected toxicity

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m−2 by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1–9) per patient. The median cumulative dose was 449 mg m−2. Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1–50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4–52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h−1 m−2 and an area under the curve of 6.00 μg ml−1 h−1 was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance. © 1999 Cancer Research Campaig

Іншомовні аспекти фахової між культурної комунікації в сучасній вітчизняній і зарубіжній науковій літературі

У статті розглядаються основні напрямки сучасних вітчизняних і зарубіжних наукових досліджень з іншомовної фахової міжкультурної комунікації. Aspects of the professional foreign language of intercultural communication in modern domestic and foreign scientific literature. The paper discusses the main directions of current domestic and foreign scientific research in the field of professional foreign language intercultural communication

Mn bioavailability by polarized Caco-2 cells: comparison between Mn gluconate and Mn oxyprolinate

<p>Abstract</p> <p>Background</p> <p>Micronutrient inadequate intake is responsible of pathological deficiencies and there is a need of assessing the effectiveness of metal supplementation, frequently proposed to rebalance poor diets. Manganese (Mn) is present in many enzymatic intracellular systems crucial for the regulation of cell metabolism, and is contained in commercially available metal supplements.</p> <p>Methods</p> <p>We compared the effects of two different commercial Mn forms, gluconate (MnGluc) and oxyprolinate (MnOxP). For this purpose we used the polarized Caco-2 cells cultured on transwell filters, an established in vitro model of intestinal epithelium. Since micronutrient deficiency may accelerate mitochondrial efficiency, the mitochondrial response of these cells, in the presence of MnGluc and MnOxP, by microscopy methods and by ATP luminescence assay was used.</p> <p>Results</p> <p>In the presence of both MnOxP and MnGluc a sustained mitochondrial activity was shown by mitoTraker labeling (indicative of mitochondrial respiration), but ATP intracellular content remained comparable to untreated cells only in the presence of MnOxP. In addition MnOxP transiently up-regulated the antioxidant enzyme Mn superoxide dismutase more efficiently than MnGluc. Both metal treatments preserved NADH and βNADPH diaphorase oxidative activity, avoided mitochondrial dysfunction, as assessed by the absence of a sustained phosphoERK activation, and were able to maintain cell viability.</p> <p>Conclusions</p> <p>Collectively, our data indicate that MnOxP and MnGluc, and primarily the former, produce a moderate and safe modification of Caco-2 cell metabolism, by activating positive enzymatic mechanisms, thus could contribute to long-term maintenance of cell homeostasis.</p

Pituitary Adenylate Cyclase Activating Peptide (1-38) and its analog (Acetyl-[Ala15, Ala20] PACAP 38-polyamide) reverse methacholine airway hyperresponsiveness in rats

O objetivo deste estudo foi investigar funcionalmente e estruturalmente efeito broncodilatador do peptídeo ativador da adenilato ciclase pituitária (PACAP1-38) e da acetil-[Ala15, Ala20]PACAP 38-poliamida, potente análogo do PACAP-38, nos ratos desafiados pelo metacolina (MeCh). Ratos Wistar machos foram aleatoriamente divididos em cinco grupos. Grupos 1 e 2, inalando aerossóis de solução salina ou doses crescentes de MeCh (0,5, 1, 2,12, 4,25, 8,5, 17, 34 e 68 mg/L). Os outros grupos recebendo terbutalina (Terb) (250 µg/rato) (10-6M), PACAP-38 (50 µg/rato) (0.1 mM) ou análogo do PACAP-38 (50 µg/rato) associados a MeCh na dose de 4,25 mg/L. A resistência pulmonar total (RL) foi registrada antes e 2 min após a administração de Mech pelo equipamento pneumomultiteste. A administração MeCh induziu aumento significativo e dose dependente (pThe aim of this study was to investigate both functionally and structurally bronchodilator effects of Pituitary adenylate cyclase activating peptide (PACAP38) and acetyl-[Ala15, Ala20] PACAP38-polyamide, a potent PACAP38 analog, in rats challenged by methacholine (MeCh). Male Wistar rats were divided randomly into five groups. Groups 1 and 2 inhaled respectively aerosols of saline or increasing doses of MeCh (0.5, 1, 2.12, 4.25, 8.5, 17, 34 and 68mg/L). The other groups received terbutaline (Terb) (250 µg/rat) (10-6 M), PACAP38 (50 µg/rat) (0.1 mM) or PACAP38 analog (50 µg/rat) associated to MeCh from the dose of 4.25 mg/L. Total lung resistances (RL) were recorded before and 2 min after MeCh administration by pneumomultitest equipment. MeCh administration induced a significant and a dose-dependent increase (

A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project

Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don't always mimic human physiology due to species-specific differences. Several efforts have been made to predict medication transfer into the milk based on physicochemical characteristics. However, the role of transporter proteins and several physiological factors (e.g., variable milk lipid content) are not accounted for by these methods. Physiologically-based pharmacokinetic (PBPK) modelling offers a mechanism-oriented strategy with bio-relevance. Recently, lactation PBPK models have been reported for some medications, showing at least the feasibility and value of PBP