Rest stops during road transport: Impacts on performance and acute-phase protein responses of feeder cattle

Angus x Hereford steers (n = 42) and heifers (n = 21) were ranked by gender and BW on d 0 of the experiment and randomly assigned to 1 of 3 treatments: 1) no transport and full access to feed and water (CON); 2) continuous road transport for 1,290 km (TRANS), or 3) road transport for 1,290 km, with rest stops every 430 km (STOP; total of 2 rest stops). Treatments were applied from d 0 to 1 of the experiment. Cattle from TRANS and STOP treatments were transported in separate commercial livestock trailers, within a single 2.1 x 7.2 m compartment, but through the exact same route. During each rest stop, STOP cattle were unloaded and offered mixed alfalfa-grass hay and water for ad libitum consumption for 2 h. Upon arrival of STOP and TRANS on d 1, cattle were ranked by sex and BW within each treatment and assigned to 21 feedlot pens (7 pens/treatment; 2 steers and 1 heifer/pen). Full BW was recorded before (d -1 and 0) treatment application and at the end of experiment (d 28 and 29). Total DMI was evaluated daily from d 1 to 28. Blood samples were collected on d 0 (before loading of TRANS and STOP cattle), 1 (immediately after unloading of TRANS and STOP cattle), 4, 7, 10, 14, 21, and 28. Body weight shrink from d 0 to d 1 was reduced (P < 0.01) in CON compared to TRANS and STOP, and reduced in STOP compared to TRANS. Mean ADG was greater (P < 0.05) in CON compared to TRANS and STOP, but similar (P = 0.68) between TRANS and STOP. No treatment effects were detected (P >= 0.18) on hay, concentrate, and total DMI. Mean G: F was greater (P = 0.05) in CON compared to STOP, tended to be greater (P = 0.08) in CON compared to TRANS, and similar (P = 0.85) between TRANS and STOP. Plasma cortisol concentrations were greater (P <= 0.04) in TRANS compared to CON and STOP on d 1, and greater (P = 0.04) in TRANS compared to CON on d 4. Serum NEFA concentrations were greater (P < 0.01) in TRANS compared to CON and STOP on d 1, and greater (P <= 0.05) in TRANS compared to CON on d 4 and 7. Mean plasma ceruloplasmin concentrations were similar (P = 0.19) among treatments. Plasma haptoglobin concentrations were greater (P <= 0.04) in TRANS compared to CON and STOP on d 1, and in STOP compared to CON on d 1. In conclusion, inclusion of rest stops during a 1,290-km transport prevented the increase in circulating cortisol and alleviated the NEFA and haptoglobin response elicited by transport, but did not improve feedlot receiving performance of transported cattle.

Loco-regional administration of anticancer agents : isolated lung perfusion with doxorubicin hypoxic abdominal stop-flow perfusion with gemcitabine

SUMMARY Regional drug delivery is an approach designed to improve the selectivity of anticancer chemotherapy. The advantage of regional treatments lies in increasing the drug concentration in the affected organ, while the rest of the organism is spared, thus improving efficacy and limiting treatment toxicity. The goal of this thesis was to assess the distribution throughout the body and the disposition (pharmacokinetics) of two anticancer agents, doxorubicin and gemcitabine, administered by two different regional administration modalities: isolated lung perfusion (ILP) for pulmonary metastases from soft tissue sarcomas and abdominal stop-flow hypoxic perfusion for advanced pancreatic cancers, respectively. For this purpose, two high-performance liquid chromatography methods were developed and validated. The first enabled the determination of doxorubicin in four different biological matrices: serum, reconstituted effluent, tissues with low levels of doxorubicin and tissues with high levels of doxorubicin. The second allows the analysis of gemcitabine and its principal metabolite dFdU in plasma. The administration of doxorubicin by ILP was studied in three preclinical studies (one on pigs and two on rats). It was first shown that, regardless of the administration mode, doxorubicin was not homogeneously distributed throughout the lung and that some regions remained out of reach. Secondly, it was demonstrated that doxorubicin did not adequately reach the tumours despite very high levels found in the lung. Finally, an attempt to enhance the doxorubicin tumoural uptake by pharmacologic modulation using two P-glycoprotein inhibitors, cyclosporin and valspodar, was unsuccessful. The last part of this work involves the administration of gemcitabine by abdominal stop-flow as a part of a phase I clinical trial in patients with advanced pancreatic disease or resistant malignant ascites. The study has demonstrated that the regional exposure to gemcitabine was increased while the exposure of the entire organism was similar to standard intravenous administrations. From a toxicological perspective, the procedure was rather well tolerated. However, even if no clinical response is expected from a phase I study, no hints of clinical responses were unfortunately observed. In conclusion, even if loco-regional therapies may afford the pharmacological advantage of increasing anticancer drug levels at the tumour site, further studies of these investigational treatment modalities are warranted to ascertain whether they can provide a significant improvement of the cancer therapy for patients, in terms of treatment tolerability, improved responses and survival rates. RÉSUMÉ L'administration locorégionale d'agents anticancéreux est une approche destinée à augmenter la sélectivité du traitement. L'avantage des traitements régionaux repose sur le fait que la concentration du médicament cytostatique est augmentée dans l'organe où est localisée la tumeur, alors que le reste de l'organisme est épargné, améliorant ainsi en théorie l'efficacité du traitement et en limitant sa toxicité. Le but de ce travail de thèse avait pour objectif de préciser, la pharmacocinétique au sein de l'organisme de deux agents anticancéreux, la doxorubicine et la gemcitabine, administrés par deux types de perfusions loco-régionales: la perfusion isolée du poumon (ILP) pour les métastases pulmonaires de sarcomes des tissus mous, et la perfusion hypoxique (stop-flow) abdominale pour les cancers avancés du pancréas. Dans cette optique, deux méthodes de chromatographie liquide à haute performance ont été développées et validées. La première permet le dosage de la doxorubicine dans quatre milieux biologiques: le sérum, l'effluent reconstitué, ainsi que des tissus contenant des concentrations faibles et élevées en doxorubicine. La seconde méthode permet le dosage dans le plasma de la gemcitabine et de son principal métabolite, le dFdU. L'administration de doxorubicine par ILP a été étudiée dans trois études précliniques (une chez le porc et deux chez le rat). Il a été montré, dans un premier temps, que la doxorubicine n'était pas distribuée de façon homogène au sein du poumon, quel que soit son mode d'administration. Dans un deuxième temps, il a été démontré que le médicament n'atteignait pas les tumeurs de façon adéquate, malgré des concentrations très élevées au sein du tissu pulmonaire. Finalement, une tentative d'augmenter la pénétration tumorale de la doxorubicine par une modulation pharmacologique de la P-glycoprotéine en utilisant la cyclosporine et le valspodar n'a pas abouti. La dernière partie de ce travail concernait l'administration de gemcitabine par stop-flow abdominal dans le cadre d'une étude clinique de phase I menée auprès de patients atteints de cancers avancés du pancréas ou d'ascites malignes réfractaires. Cette étude a démontré que l'exposition régionale à la gemcitabine était augmentée, alors que l'exposition de l'organisme était similaire à une administration de dose standard par voie intraveineuse. D'un point de vue toxicologique la procédure fut relativement bien tolérée. Cependant, même s'il n'est pas attendu de réponses cliniques dans une étude de phase I, aucun signe de réponse au traitement n'a pu être malheureusement observé. En conclusion, même si les thérapies loco-régionales présentent -en théorie- l'avantage pharmacologique d'augmenter les taux du médicaments anticancéreux sur le site de la tumeur, d'autres études précliniques et cliniques sont nécessaires pour démontrer que ces nouvelles modalités de traitement, de nature investigationelle à présent, apportent une réelle amélioration pour la prise en charge des patients cancéreux, en terme de tolérance au traitement et de l'augmentation des taux de réponses et de survie.

Cumulative doses of radioiodine in the treatment of differentiated thyroid carcinoma: knowing when to stop

OBJECTIVE: Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: The probability of progressive disease according to CDs was evaluated in patients < 45 years old and > 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. RESULTS: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs > 600 mCi in patients > 45 years old and with CDs > 800 mCi in patients < 45 years. CONCLUSION: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.

Ultra-Structural Changes at the Apical Stop Irradiated with CO(2) Laser

Objective: This study evaluated ultra-structural dentine changes at the apical stop after CO(2) laser irradiation used during biomechanical preparation. Background: Most studies evaluating the sealing efficiency of CO(2) lasers have been carried out after apical root canal resections and retro-filling procedures. Methods: Sixty human canines were prepared with #1 to #6 Largo burs. The apical stops were established at 1 mm (n = 30) and 2 mm (n = 30) from the apex. Final irrigation was performed with 1% NaOCl and 15% EDTA followed by 20 ml of distilled and deionized water. Specimens were subdivided into three subgroups (n = 10 for each stop distance): GI-no radiation (n = 20); GII-3W potency (n = 20), GIII-5W potency (n = 20). After preparation, specimens were evaluated by scanning electron microscopy, with ultra-structural changes classified according to a scoring system based on six qualitatively different outcomes. Results: Statistical analysis using the Mann-Whitney test confirmed more intense results for the specimens irradiated at 5 W potency than at 3 W (p<0.0001). The Kruskal-Wallis test indicated that when using the same potencies (3 or 5 W) at 1 and 2 mm from the apex, there were no statistically significant differences in ultra-structural changes. Conclusions: Our results showed that ultra-structural changes ranged from smear layer removal to dentine fusion. As laser potency was increased from 3 to 5 W, ultra-structural changes included extensive fused lava-like areas sealing the apical foramen.

Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

Background: Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases. Methods: We studied nineteen neonates (27.3 +/- 17.2 days old) with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO(2) and VCO(2) measured by gas chromatography. Results: REE significantly increased from 49.4 +/- 13.1 kcal/kg/day during the acute to 68.3 +/- 10.9 kcal/kg/day during recovery phase of sepsis (P < 0.01). Similarly, VO(2) (7.4 +/- 1.9 vs 10 +/- 1.5 ml/kg/min) and VCO(2) (5.1 +/- 1.7 vs 7.4 +/- 1.5 ml/kg/min) were also increased during the course of the disease (P < 0.01). Conclusion: REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities.

Comparison between constant and decreasing rest intervals: influence on maximal strength and hypertrophy

de Souza Jr, TP, Fleck, SJ, Simao, R, Dubas, JP, Pereira, B, de Brito Pacheco, EM, da Silva, AC, and de Oliveira, PR. Comparison between constant and decreasing rest intervals: influence on maximal strength and hypertrophy. J Strength Cond Res 24(7): 1843-1850, 2010-Most resistance training programs use constant rest period lengths between sets and exercises, but some programs use decreasing rest period lengths as training progresses. The aim of this study was to compare the effect on strength and hypertrophy of 8 weeks of resistance training using constant rest intervals (CIs) and decreasing rest intervals (DIs) between sets and exercises. Twenty young men recreationally trained in strength training were randomly assigned to either a CI or DI training group. During the first 2 weeks of training, 3 sets of 10-12 repetition maximum (RM) with 2-minute rest intervals between sets and exercises were performed by both groups. During the next 6 weeks of training, the CI group trained using 2 minutes between sets and exercises (4 sets of 8-10RM), and the DI group trained with DIs (2 minutes decreasing to 30 seconds) as the 6 weeks of training progressed (4 sets of 8-10RM). Total training volume of the bench press and squat were significantly lower for the DI compared to the CI group (bench press 9.4%, squat 13.9%) and weekly training volume of these same exercises was lower in the DI group from weeks 6 to 8 of training. Strength (1RM) in the bench press and squat, knee extensor and flexor isokinetic measures of peak torque, and muscle cross-sectional area (CSA) using magnetic resonance imaging were assessed pretraining and posttraining. No significant differences (p <= 0.05) were shown between the CI and DI training protocols for CSA (arm 13.8 vs. 14.5%, thigh 16.6 vs. 16.3%), 1RM (bench press 28 vs. 37%, squat 34 vs. 34%), and isokinetic peak torque. In conclusion, the results indicate that a training protocol with DI is just as effective as a CI protocol over short training periods (6 weeks) for increasing maximal strength and muscle CSA; thus, either type of program can be used over a short training period to cause strength and hypertrophy.

Manipulation of rest period length induces different causes of fatigue in vertical jumping

The aim of this study was to directly compare the causes of fatigue after a short- and a long-rest interval between consecutive stretch-shortening cycle exercises. Eleven healthy males jumped with different resting period lengths (short = 6.1 +/- 1 s, long = 8.6 +/- 0.9 s), performing countermovement jumps at 95% of their maximal jump height until they were unable to sustain the target height. After short- and long-rest, the maximal voluntary isometric contraction knee extension torque decreased (-7%; p = 0.04), comparing to values obtained before exercise protocols. No change was seen from pre- to post-exercise, for either short- or long-rest, in biceps femoris coactivation (-1%; p = 0.95), peak-to-peak amplitude (1%; p = 0.95) and duration (-8%; p = 0.92) of the compound muscle action potential of the vastus lateralis. Evoked peak twitch torque reduced after both exercise protocols (short = -26%, long = -32%; p = 0.003) indicating peripheral fatigue. However, central fatigue occurred only after short-rest evidenced by a reduction in voluntary activation of the quadriceps muscle (-14%; p = 0.013) measured using the interpolated twitch technique. In conclusion, after Stretch-shortening cycle exercise using short rest period length, the cause of fatigue was central and peripheral, while after using long rest period length, the cause of fatigue was peripheral.

Dipyridamole Stress and Rest Myocardial Perfusion by 64-Detector Row Computed Tomography in Patients With Suspected Coronary Artery Disease

Recently, stress myocardial computed tomographic perfusion (CTP) was shown to detect myocardial ischemia. Our main objective was to evaluate the feasibility of dipyridamole stress CTP and compare it to single-photon emission computed tomography (SPECT) to detect significant coronary stenosis using invasive conventional coronary angiography (CCA; stenosis >70%) as the reference method. Thirty-six patients (62 +/- 8 years old, 20 men) with previous positive results with SPECT (<2 months) as the primary inclusion criterion and suspected coronary artery disease underwent a customized multidetector-row CT protocol with myocardial perfusion evaluation at rest and during stress and coronary CT angiography (CTA). Multidetector-row computed tomography was performed in a 64-slice scanner with dipyridamole stress perfusion acquisition before a second perfusion/CT angiographic acquisition at rest. Independent blinded observers performed analysis of images from CTP, CTA, and CCA. All 36 patients completed the CT protocol with no adverse events (mean radiation dose 14.7 +/- 3.0 mSv) and with interpretable scans. CTP results were positive in 27 of 36 patients (75%). From the 9 (25%) disagreements, 6 patients had normal coronary arteries and 2 had no significant stenosis (8 false-positive results with SPECT, 22%). The remaining patient had an occluded artery with collateral flow confirmed by conventional coronary angiogram. Good agreement was demonstrated between CTP and SPECT on a per-patient analysis (kappa 0.53). In 26 patients using CCA as reference, sensitivity, specificity, and positive and negative predictive values were 88.0%, 79.3%, 66.7%, and 93.3% for CTP and 68.8, 76.1%, 66.7%, and 77.8%, for SPECT, respectively (p = NS). In conclusion, dipyridamole CT myocardial perfusion at rest and during stress is feasible and results are similar to single-photon emission CT scintigraphy. The anatomical-perfusion information provided by this combined CT protocol may allow identification of false-positive results by SPECT. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:310-315)

The Carvedilol`s Beta-Blockade in Heart Failure and Exercise Training`s Sympathetic Blockade in Healthy Athletes during the Rest and Peak Effort

In recent years, beta-blocker therapy has become a primary pharmacologic intervention in patients with heart failure by blocking the sympathetic activity. To compare the exercise training`s sympathetic blockade in healthy subjects (athletes) and the carvedilol`s sympathetic blockade in sedentary heart failure patients by the evaluation of the heart rate dynamic during an exercise test. A total of 26 optimized and 49 nonoptimized heart failure patients in a stable condition (for, at least, 3 months), 15 healthy athletes and 17 sedentary healthy subjects were recruited to perform a cardiopulmonary exercise test. The heart rate dynamic (rest, reserve, peak and the peak heart rate in relation to the maximum predicted for age) was analyzed and compared between the four groups. The heart rate reserve was the same between optimized (48 +/- 15) and nonoptimized (49 +/- 18) heart failure patients (P < 0.0001). The athletes (188 +/- 9) showed a larger heart rate reserve compared to sedentary healthy subjects (92 +/- 10, P < 0.0001). Athletes and healthy sedentary reached the maximum age-predicted heart ratefor their age, but none of the heart failure patients did. The carvedilol`s sympathetic blockade occurred during the rest and during the peak effort in the same proportion, but the exercise training`s sympathetic blockade in healthy subjects occurred mainly in the rest.

Scheduling of head-dependent cascaded reservoirs considering discharge ramping constraints and start/stop of units

This paper is on the problem of short-term hydro scheduling (STHS), particularly concerning head-dependent reservoirs under competitive environment. We propose a novel method, based on mixed-integer nonlinear programming (MINLP), for optimising power generation efficiency. This method considers hydroelectric power generation as a nonlinear function of water discharge and of the head. The main contribution of this paper is that discharge ramping constraints and start/stop of units are also considered, in order to obtain more realistic and feasible results. The proposed method has been applied successfully to solve two case studies based on Portuguese cascaded hydro systems, providing a higher profit at an acceptable computation time in comparison with classical optimisation methods based on mixed-integer linear programming (MILP).

As relações intergeracionais e as sociedades envelhecidas : Envelhecer numa sociedade não Stop – O território multigeracional de Lisboa Oriental

A dissertação de mestrado subordinada ao tema das Relações Intergeracionais e as Sociedades Envelhecidas surgiu, no âmbito do Mestrado em Educação Social e Intervenção Comunitária, da Escola Superior de Educação de Lisboa e teve como ponto de partida saber se a participação em actividades intergeracionais promove o envelhecimento ativo de 8 mulheres com 65 e mais anos, residentes num território multigeracional de Lisboa Oriental. A abordagem concetual do envelhecimento social, do envelhecimento ativo, das relações intergeracionais e da participação conduziu o estudo, através da triangulação dos instrumentos de análise qualitativa de entrevistas de histórias de vida e de focus group. As mulheres entrevistadas têm entre 65 e 85 anos de idade cronológica, mas em média dizem sentir que têm menos 34 anos. Afirmam, ser jovens de espirito e por isso preferem ser chamadas de seniores. Manifestam que sempre foram e são, mulheres autónomas, livres, independentes, com poder de decisão, com auto-estima elevada e com qualidade de vida. Mulheres que ocupam o tempo em actividades da vida diária, em actividades de tempos livres, e voluntariado. Mulheres reivindicativas, proativas, frontais e determinadas que assumem um papel social ativo envolvendo-se socialmente em todas as actividades produtivas ou orientadas para a performance e em actividades colectivas e ou orientadas para a união, com vista alcançar objetivos comuns. Mulheres, que ganham prestígio e estatuto na comunidade por se envolverem socialmente no processo de tomadas de decisão, organização, execução e avaliação, com as gerações mais novas. São visionárias ancestrais de espirito jovem que abrem novas portas para a construção social da velhice nas sociedades neoliberais e desafiam os humanistas quando afirmam que as atividades produtivas na velhice dão sentido à própria existência. São histórias de mulheres que nos fazem acreditar que a participação social contribui espontaneamente para o diálogo entre as gerações, em todas as fases da vida. - Abstract A dissertation on the subject of Intergenerational Relationships and Societies Aged emerged within the Master of Education Social and Community Intervention, School of Education and Lisbon had as starting point whether participation promotes intergenerational activities on aging 8 active women aged 65 years and older, residing in the territory of Eastern Lisbon multigenerational. The conceptual approach of social aging, active aging, intergenerational relations and participation conducted the study through triangulation of instruments qualitative analysis of interviews and life stories focus group. The women interviewed are between 65 and 85 years of chronological age, but on average say they feel they are under 34 years old. They claim to be young in spirit and so they prefer to be called seniors. Demonstrate that have always been and are women autonomous, free, independent, decision-making, self-esteem and quality of life. Women who occupy the time in activities of daily life, in leisure activities, and volunteering. Women reivindicativas, proactive, front and determined to play an active social role by engaging in socially productive activities or any performance-oriented and collective activities and or targeted at the union in order to achieve common objectives. Women who gain prestige and status in the community by becoming involved socially in the process of decision making, organization, implementation and evaluation with the younger generations. They are young visionary spirit of ancestors that open new doors to the social construction of old age in neoliberal societies and challenge humanists say when productive activities in old age give meaning to their own existence. These are stories of women who have us believe that social participation contributes to spontaneous dialogue between generations, in all stages of life.