Drugs that impair driving: student manual.

Mode of access: Internet.

Los Angeles County Alcohol Safety Action Project/ L.A. Police Department: driver impairment study. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Test drivers in the Daimler-Benz driving simulator with drivers under diphenhydramine. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Heat stress, heat strain, and productivity in Washington State tree fruit harvesters

Thesis (Master's)--University of Washington, 2016-06

The use of hypertonic saline for treating intracranial hypertension after traumatic brain injury

The past decade has witnessed a resurgence of interest in the use of hypertonic saline for low-volume resuscitation after trauma. Preliminary studies suggested that benefits are limited to a subgroup of trauma patients with brain injury, but a recent study of prehospital administration of hypertonic saline to patients with traumatic brain injury failed to confirm a benefit. Animal and human studies have demonstrated that hypertonic saline has clinically desirable physiological effects on cerebral blood flow, intracranial pressure, and inflammatory responses in models of neurotrauma. There are few clinical studies in traumatic brain injury with patient survival as an end point. In this review, we examined the experimental and clinical knowledge of hypertonic saline as an osmotherapeutic agent in neurotrauma.

Transient temperature rise in a mouse due to low-frequency regional hyperthermia

A refined nonlinear heat transfer model of a mouse has been developed to simulate the transient temperature rise in a neoplastic tumour and neighbouring tissue during regional hyperthermia using a 150 kHz inductive coil. In this study, we incorporate various bio-energetic enhancements to the heat transfer equation and numerical validations based on experimental findings for the mouse, in terms of nonlinear metabolic heat production, homeothermy, blood perfusion parameters, thermoregulation, psychological and physiological effects. The discretized bio-heat transfer equation has been validated with the commercial software FEMLAB on a canonical multi-sphere object before applying the scheme to the inhomogeneous mouse voxel phantom. The time-dependent numerical results of regional hyperthermia of mouse thigh have been compared with the available experimental temperature results with only a few small disparities. During the first 20 min of local unfocused heating, the temperature in the tumour and the surrounding tissue increased by around 7.5 degrees C. The objective of this preliminary study was to develop a validated electrothermal numerical scheme for inductive hyperthermia of a small mammal with the intention of expanding the model into a complete numerical solution involving ferromagnetic nanoparticles for targeted heating of tumours at low frequencies. In addition, the numerical scheme herein could assist in optimizing and tailoring of focused electromagnetic fields for hyperthermia.

Optimal crossover designs for logistic regression models in pharmacodynamics

Pharmacodynamics (PD) is the study of the biochemical and physiological effects of drugs. The construction of optimal designs for dose-ranging trials with multiple periods is considered in this paper, where the outcome of the trial (the effect of the drug) is considered to be a binary response: the success or failure of a drug to bring about a particular change in the subject after a given amount of time. The carryover effect of each dose from one period to the next is assumed to be proportional to the direct effect. It is shown for a logistic regression model that the efficiency of optimal parallel (single-period) or crossover (two-period) design is substantially greater than a balanced design. The optimal designs are also shown to be robust to misspecification of the value of the parameters. Finally, the parallel and crossover designs are combined to provide the experimenter with greater flexibility.

Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age

Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD) fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein) or normal protein diet (18% casein; NPD) was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively), throughout gestation (LPD, NPD) or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD). LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD). LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr) and insulin-like growth factor I receptor (Igf1r) in retroperitoneal fat was significantly elevated in Emb-LPD females (P&0.05), whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1) gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring health. © 2011 Watkins et al.

Receptor activity-modifying proteins 2 and 3 generate adrenomedullin receptor subtypes with distinct molecular properties

Adrenomedullin (AM) is a peptide hormone with numerous effects in the vascular systems. AM signals through the AM1 and AM2 receptors formed by the obligate heterodimerization of a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins (RAMP) 2 and 3, respectively. These different CLR-RAMP interactions yield discrete receptor pharmacology and physiological effects. The effective design of therapeutics that target the individual AM receptors is dependent on understanding the molecular details of the effects of RAMPs on CLR. To understand the role of RAMPs 2 and 3 on the activation and conformation of the CLR subunit of AM receptors we mutated 68 individual amino acids in the juxtamembrane region of CLR, a key region for activation of AM receptors and determined the effects on cAMP signalling. Sixteen CLR mutations had differential effects between the AM1 and AM2 receptors. Accompanying this, independent molecular modelling of the full-length AM-bound AM1 and AM2 receptors predicted differences in the binding pocket, and differences in the electrostatic potential of the two AM receptors. Druggability analysis indicated unique features that could be used to develop selective small molecule ligands for each receptor. The interaction of RAMP2 or RAMP3 with CLR induces conformational variation in the juxtamembrane region, yielding distinct binding pockets, probably via an allosteric mechanism. These subtype-specific differences have implications for the design of therapeutics aimed at specific AM receptors and for understanding the mechanisms by which accessory proteins affect G protein-coupled receptor function.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Efeitos dos exercícios aeróbio contínuo e intervalado na variabilidade da frequência cardíaca em adultos jovens saudáveis. Ensaio clínico aleatório

The high-intensity interval exercise has been described as an option for increasing physical activity and its use also being suggested in the therapeutic management of many conditions such as diabetes mellitus and heart failure. However, the knowledge of its physiological effects and parameters that can assure greater safety for interval exercise prescription; especially its effect on short- and medium-term (24 hours after exercise) exercise recovery, need to be clarified. This study objective was to evaluate the effect of continuous and interval aerobic exercise on the cardiac autonomic control immediate and medium term (24 hours), by assessing heart rate variability (HRV). The present study is a randomized crossover clinical trial in which healthy young individuals with low level of physical activity had the VFC 24 hours measured by a heart rate sensor and portable accelerometer (3D eMotion HRV, Kuopio, Finland) before and after continuous aerobic exercise (60-70% HR max, 21 min.) and interval exercise (cycle 1 min. 80-90% HR max, 2 min. at 50-60% HR max, duration 21 min.). HRV was measured in the time and frequency domain and the sympathovagal balance determined by the ratio LF / HF. Nonlinear evaluation was calculated by Shannon entropy. The data demonstrated delayed heart rate recovery immediate after exercise and lower HR after 24 hours compared to pre intervention values, especially in the interval exercise group. There was a tendency to higher predominance and representatives index values of sympathetic stimulation during the day in interval exercise group; however, without statistical significance. The study results help to clarify the effects of interval exercise on the 24 hours following interval exercise, setting parameters for prescription and for further evaluation of groups with metabolic and cardiovascular diseases.

Alterações fisiológicas causadas por fungicidas em soja infectada naturalmente por oídio

Soybean crop is substantially important for both Brazilian and international markets. A relevant disease that affects soybeans is powdery mildew, caused by fungus Erysiphe diffusa. The objective of this master’s thesis was to analyze physiological changes produced by fungicides in two greenhouse-grown soybean genotypes (i.e., Anta 8500 RR and BRS Santa Cruz RR) naturally infected with powdery mildew. A complete randomized block design was used with six replications in a 2x5 factorial arrangement. Treatments consisted of applications of Azoxystrobin, Biofac (fermented solution of Penicillium sp.), Carbendazim or Picoxystrobin fungicides, and a Control (no fungicide application). Three applications were performed in the experimental period, and each eventually represented a period of data collection. Gas exchanges, chlorophyll content, fluorescence of chlorophyll a and disease severity were measured twice a week. Dry grain mass production was measured at the end of the experiment. Areas under progression curve of variables were submitted to both ANOVA and Tukey’s test at 5% significance. Treatments Azoxystrobin, Biofac and Picoxystrobin had higher photosynthetic rates than Control in the second period, with genotype Anta having higher rate than Santa Cruz. Biofac had higher transpiration rate than Control in the second period, while Biofac and Picoxystrobin had higher figures in Santa Cruz in the third period. Carbendazim had greater stomatal conductance in Anta, whilst Azoxystrobin, Biofac and Picoxystrobin had greater values than Carbendazim in Santa Cruz. Biofac and Picoxystrobin had greater intercellular CO2 concentration in Santa Cruz. Azoxystrobin and Picoxystrobin had greater instantaneous water use efficiency than Control, with Anta being more efficient than Santa Cruz. Biofac and Picoxystrobin had greater intrinsic water use efficiency in Anta, while Carbendazim increased efficiency in Santa Cruz. Azoxystrobin, Biofac and Picoxystrobin had greater carboxylation efficiency than Control in the second period, with Anta being more efficient than Santa Cruz. Azoxystrobin and Biofac had greater contents of chlorophylls a, b and a+b than Control in the second period. Azoxystrobin had greater effective quantum yield than Control and Picoxystrobin. All treatments faced increasing disease severity over time, with Anta being less resistant than Santa Cruz. As for production, data showed that: (1) Santa Cruz was more productive than Anta, having the greatest dry grain mass with Carbendazim, and (2) Anta’s lower disease severity did not translate into higher productions. In conclusion, strobilurins (Azoxystrobin and Picoxystrobin) and Biofac performed similarly as to their physiological effects on soybeans; however, these effects did not lead to increased dry grain mass by the end of the experiment.

Climate Change Influences Carrying Capacity in a Coastal Embayment Dedicated to Shellfish Aquaculture

A spatially explicit coupled hydrodynamic-biogeochemical model was developed to study a coastal ecosystem under the combined effects of mussel aquaculture, nutrient loading and climate change. The model was applied to St Peter's Bay (SPB), Prince Edward Island, Eastern Canada. Approximately 40 % of the SPB area is dedicated to mussel (Mytilus edulis) longline culture. Results indicate that the two main food sources for mussels, phytoplankton and organic detritus, are most depleted in the central part of the embayment. Results also suggest that the system is near its ultimate capacity, a state where the energy cycle is restricted to nitrogen-phytoplankton-detritus-mussels with few resources left to be transferred to higher trophic levels. Annually, mussel meat harvesting extracts nitrogen (N) resources equivalent to 42 % of river inputs or 46.5 % of the net phytoplankton primary production. Under such extractive pressure, the phytoplankton biomass is being curtailed to 1980's levels when aquaculture was not yet developed and N loading was half the present level. Current mussel stocks also decrease bay-scale sedimentation rates by 14 %. Finally, a climate change scenario (year 2050) predicted a 30 % increase in mussel production, largely driven by more efficient utilization of the phytoplankton spring bloom. However, the predicted elevated summer temperatures (> 25 A degrees C) may also have deleterious physiological effects on mussels and possibly increase summer mortality levels. In conclusion, cultivated bivalves may play an important role in remediating the negative impacts of land-derived nutrient loading. Climate change may lead to increases in production and ecological carrying capacity as long as the cultivated species can tolerate warmer summer conditions.

Energy and Antioxidant Responses of Pacific Oyster Exposed to Trace Levels of Pesticides

Here, we assess the physiological effects induced by environmental concentrations of pesticides in Pacific oyster Crassostrea gigas. Oysters were exposed for 14 d to trace levels of metconazole (0.2 and 2 mu g/L), isoproturon (0.1 and 1 mu g/L), or both in a mixture (0.2 and 0.1 mu g/L, respectively). Exposure to trace levels of pesticides had no effect on the filtration rate, growth, and energy reserves of oysters. However, oysters exposed to metconazole and isoproturon showed an overactivation of the sensing-kinase AMP-activated protein kinase alpha (AMPK alpha), a key enzyme involved in energy metabolism and more particularly glycolysis. In the meantime, these exposed oysters showed a decrease in hexokinase and pyruvate kinase activities, whereas 2-DE proteomic revealed that fructose-1,6-bisphosphatase (F-1,6-BP), a key enzyme of gluconeogenesis, was upregulated. Activities of antioxidant enzymes were higher in oysters exposed to the highest pesticide concentrations. Both pesticides enhanced the superoxide dismutase activity of oysters. Isoproturon enhanced catalase activity, and metconazole enhanced peroxiredoxin activity. Overall, our results show that environmental concentrations of metconazole or isoproturon induced subtle changes in the energy and antioxidant metabolisms of oysters.

Produção de nanopartículas contendo peptídeos bioativos de microalgas

A produção de peptídeos bioativos de distintas fontes de proteínas vem ganhando espaço na produção científica e tecnológica, despertando interesse do setor empresarial. Paralelamente a isso, devido à elevada concentração de proteínas na biomassa das microalgas Spirulina e Chlorella, estas apresentam grande potencial para a extração de biocompostos com alto valor agregado, como biopeptídeos de microalgas. As proteínas são uma importante fonte de peptídeos bioativos, mas estes não estão ativos na proteína precursora e devem ser liberados para que apresentem efeitos fisiológicos desejados. Essa liberação pode ser feita através de hidrólise enzimática a partir de proteases, sendo um dos métodos mais utilizados para a produção destes biocompostos. Dentro deste contexto, vários estudos vêm mostrando o uso da tecnologia por secagem em spray dryer para a obtenção de nanopartículas que contenham compostos bioativos, sendo, essa técnica, amplamente utilizada para transformar líquidos em pós, podendo ser aplicada em materiais sensíveis à temperatura. Este estudo teve como objetivo obter peptídeos bioativos através da reação enzimática, tendo como substrato a biomassa de Spirulina sp. LEB 18 e Chlorella pyrenoidosa e, na sequência, obter nanopartículas contendo os biopeptídeos. Primeiramente, foram testadas as 3 proteases comerciais (Protemax 580 L, Protemax N 200 e pepsina) para a produção de hidrolisados proteicos de microalgas, para isso foram realizados 3 delineamentos compostos centrais para cada microalga em estudo (Chlorella e Spirulina). Os delineamentos utilizados foram do tipo 23 com três repetições no ponto central, variando-se a concentração de enzima (5 a 10 U.mL-1), a concentração de substrato (5 a 10 %) e o tempo de reação (60 a 240 min). Após, realizou-se 2 delineamentos compostos rotacionais do tipo 22 com pontos centrais, um para cada microalga, utilizando-se para a hidrólise a enzima Protemax 580L (5 U.mL-1) variando-se a concentração de substrato e tempo de reação, para todos ensaios estudou-se a solubilidade, capacidade de retenção de água, atividade antioxidante e digestibilidade. Foi selecionado um ensaio para cada microalga, levando em conta os melhores resultados. Então nova hidrólise enzimática foi realizada sendo o sistema reacional composto pela enzima Protemax 580 L (5 U.mL-1) e pela biomassa de Spirulina sp. LEB 18 ou Chlorella pyrenoidosa (4% de proteína) durante tempo de 200 min. Os hidrolisados foram purificados por filtração a vácuo com membranas millipores de diferentes tamanhos (0,45; 0,2 e 0,1 µm) e por colunas com membrana vertical Amicon® Ultra 0.5 (3K e 10K), sendo que após cada etapa, foi realizado teste de atividade antioxidante pelos métodos de poder redutor, DPPH e ABTS, a fim de verificar a permanência da atividade antioxidante. Utilizou-se nano spray dryer Büchi modelo B 90 para a secagem das amostras, sendo o tamanho das partículas obtidas analisados por microscopia eletrônica de varredura (MEV). Por fim, conclui-se que a biomassa de microalgas pode ser utilizada como fonte de produção de peptídeos bioativos com elevada atividade antioxidante e que dentre as microalgas estudadas, Spirulina sp. LEB 18 apresentou melhores resultados, em todas as análises realizadas, quando comparada com Chlorella pyrenoidosa. Esse estudo, também visou utilizar a nanobiotecnologia para obtenção de nanoparículas contendo os biopeptídeos, para tal, utilizou-se o nano Buchi Spray Dryer B-90, o qual gerou partículas nanométricas de 14 a 18 nm para o hidrolisado de Spirulina e de 72 a 108 nm para o hidrolisado de Chlorella.