Combined effect of cyclosporine and sirolimus on improving the longevity of recombinant adenovirus-mediated transgene expression in the retina

Objectives: To reevaluate the longevity and intraocular safety of recombinant adenovirus (rAd)-mediated gene delivery after subretinal injection, and to prolong transgene expression through the combination of 2 synergistic immunosuppressants. Methods: An rAd vector carrying green fluorescent protein (GFP) gene was delivered subretinally in the rat eye. The GFP expression was monitored in real time by fundus fluorescent photography. Intraocular safety was examined by observation of changes of retinal pigmentation, cell infiltration in virus-contacted area, immunophenotyping for CD4(+) and CD8(+) cytotoxic T lymphocytes, and CD68(+) macrophages, histologic findings, and dark-adapted electroretinography. Two synergistic immunosuppressants, cyclosporine and sirolimus, were used alone or in combination to prolong transgene expression by temporary immunosuppression. Results: The GFP expression peaked on day 4, dramatically decreased on day 10, and was not detectable on day 14. The decreased GFP expression was coincident with cell infiltration in virus-contacted area. Immunostaining showed that the infiltrating cells were CD4(+) and CD8(+) cytotoxic T lymphocytes and CD68(+) macrophages. Clumped retinal pigmentation and decreased b wave of dark-adapted electroretinogram were observed at 3 to 4 weeks after injection. Histologic examination confirmed rAd-induced retinal degeneration. Transient immunosuppression by cyclosporine and sirolimus, either alone or in combination, improved transgene expression, with the combination being the most efficient. The combined immunosuppression attenuated but did not retard the rAd-induced retinal damage. Conclusions: Transgene expression mediated by rAd after subretinal delivery is short-term and toxic to the retina. Combination of cyclosporine and sirolimus may act as an immunosuppressive adjunct to prolong rAd-mediated gene transfer. Clinical Relevance: The intraocular safety of rAd should be carefully considered before clinical trials are performed.

The effect of obstacle position on reach-to-grasp movements

Numerous everyday tasks require the nervous system to program a prehensile movement towards a target object positioned in a cluttered environment. Adult humans are extremely proficient in avoiding contact with any non-target objects (obstacles) whilst carrying out such movements. A number of recent studies have highlighted the importance of considering the control of reach-to-grasp (prehension) movements in the presence of such obstacles. The current study was constructed with the aim of beginning the task of studying the relative impact on prehension as the position of obstacles is varied within the workspace. The experimental design ensured that the obstacles were positioned within the workspace in locations where they did not interfere physically with the path taken by the hand when no obstacle was present. In all positions, the presence of an obstacle caused the hand to slow down and the maximum grip aperture to decrease. Nonetheless, the effect of the obstacle varied according to its position within the workspace. In the situation where an obstacle was located a small distance to the right of a target object, the obstacle showed a large effect on maximum grip aperture but a relatively small effect on movement time. In contrast, an object positioned in front and to the right of a target object had a large effect on movement speed but a relatively small effect on maximum grip aperture. It was found that the presence of two obstacles caused the system to decrease further the movement speed and maximum grip aperture. The position of the two obstacles dictated the extent to which their presence affected the movement parameters. These results show that the antic ipated likelihood of a collision with potential obstacles affects the planning of movement duration and maximum grip aperture in prehension.

Mass balance characterisation of Al-7Si-Mg alloy microstructures as a function of solution treatment time

Mass balance calculations were performed to model the effect of solution treatment time on A356 and A357 alloy microstructures. Image analysis and electron probe microanalysis were used to characterise microstructures and confirm model predictions. In as-cast microstructures, up to 8 times more Mg is tied up in the pi-phase than in Mg2Si. The dissolution of pi is accompanied by a corresponding increase in the amount of beta-phase. This causes the rate of pi dissolution to be limited by the rate of beta formation. It is predicted that solution treatments of the order of tens of minutes at 540degreesC produce near-maximum T6 yield strengths, and that Mg contents in excess of 0.52 wt% have no advantage.

The effect of mode of exposure to Beauveria bassiana on conidia acquisition and host mortality of Colorado potato beetle, Leptinotarsa decemlineata

The effects of the mode of exposure of second instar Colorado potato beetles to Beauveria bassiana on conidia acquisition and resulting mortality were investigated in laboratory studies. Larvae sprayed directly with a B, bassiana condial suspension, larvae exposed to B, bassiana-treated foliage, and larvae both sprayed and exposed to treated foliage experienced 76, 34, and 77% mortality, respectively. The total number of conidia and the proportion of germinating conidia were measured over time for four sections of the insect body: the ventral surface of the head (consisting mostly of ventral mouth parts), the ventral abdominal surface, the dorsal abdominal surface, and the legs. From observations at 24 and 36 h posttreatment, mean totals of 161.1 conidia per insect were found on sprayed larvae, 256.1 conidia on larvae exposed only to treated foliage, and 408.3 conidia on larvae both sprayed and exposed to treated foliage, On sprayed larvae, the majority of conidia were found on the dorsal abdominal surface, whereas conidia were predominantly found in the ventral abdominal surface and mouth parts on larvae exposed to treated foliage, Between 24 and 36 h postinoculation the percentage of conidia germinating on sprayed larvae increased slightly from 80 to 84%), On the treated foliage, the percentage of germinated conidia on larvae increased from 35% at 24 h to 50% at 36 h posttreatment, Conidia germination on sprayed larvae on treated foliage was 65% at 24 h and 75% at 36 h posttreatment, It is likely that the gradual acquisition of conidia derived from the continuous exposure to B. bassiana inoculum on the foliar surface was responsible for the increase in germination over time on larvae exposed to treated foliage, The density and germination of conidia were observed 0, 4, 8, 12, 16, 20, and 24 h after being sprayed with or dipped in conidia suspensions or exposing insects to contaminated foliage, Conidia germinated twice as fast on sprayed insects as with any other treatment within the first 12 h, This faster germination may be due to the pressure of the sprayer enhancing conidial lodging on cuticular surfaces. (C) 2001 Academic Press.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production. (C) 2001 Wiley-Liss, Inc.

Emotional distress induced rhabdomyolysis in an individual with carnitine palmitolytransferase deficiency

A 48-year-old male patient with underlying CPT II enzyme deficiency is described. Emotional stress appeared to precipitate recurrent myalgias, rhabdomyolysis and reversible renal impairment over a 40-year period. Our search of the English literature indicates this to be the first time that the emotional stress has been documented to precipitate the CPT II syndrome. Although the pathogenesis of this syndrome has yet to be established, existing knowledge is briefly reviewed and the likely metabolic and neuroendocrine mechanisms which link emotional stress to muscle metabolism are examined. These mechanisms influence the extent of lipolysis or glycolysis that occurs during the process of muscle ATP generation. It is suggested that neuroendocrine and other stress related changes which favour lipolysis over glycolysis adversely effect muscle energy metabolism in patients whose mitochondria are deficient in CPT II enzyme. Possible treatment strategies are those that favour glycolysis over fatty acid metabolism and include a variety of ways of modulating sympathetic and parasympathetic tone. The use of carbohydrate supplementation P-blockers and anxiolytic agents is discussed.

Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease

Background: Supplementation with propionyl-L-carnitine (PLC) may be of use in improving the exercise capacity of people with peripheral arterial disease. Methods: After a 2-wk exercise familiarization phase, seven subjects displaying intermittent claudication were studied over a 12-wk period consisting of three 4-wk phases, baseline (B), supplementation (S), and placebo (P). PLC was supplemented at 2 g(.)d(-1), and subjects were blinded to the order of supplementation. Unilateral calf strength and endurance were assessed weekly. Walking performance was assessed at the end of each phase using an incremental protocol, during which respiratory gases were collected. Results: Although there was not a significant increase in maximal walking time (similar to 14%) in the whole group, walking time improved to a greater extent than the individual baseline coefficient of variation in four of the seven subjects. The changes in walking performance were correlated with changes in the respiratory exchange ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end of S. Changes in calf strength from B to S were modestly related to changes in walking performance (r = 0.56). No improvements in calf endurance were detected throughout the study. Conclusions: These preliminary data suggest that, in addition to walking performance, muscle strength can be increased in PAD patients after 4 wk of supplementation with propionyl-L-carnitine.

Effect of gender on ownership and income in veterinary practice

Objective To estimate the effect of gender on ownership and income in veterinary practice in Australia. Methods Questionnaire completed by private veterinary practitioners, and analysed using the SAS System for Windows 7.0. Results More than three-quarters (78%) of male but 36% of female private practitioners were partial or sole owners of practices. The median annual income for all male practitioners working more than 40 hours/week was $70K, but that for females was $43K. These disparities existed in both city and country practices, and in the case of income it increased with increasing time in the workforce. Male practice owners also reported higher incomes than female owners. Conclusions Female veterinary practitioners are less likely to own practices, and more likely to earn low incomes than males. These differentials do not appear to be due to location, hours worked or years since graduation or, in the case of income, to whether they are owners or employees. The evidence points to a lower interest by women than men in the business aspects of veterinary practice.

Effect of fruit maturity on the response of 'Kensington' mango fruit to heat treatment

The effects of conditioning and hot water treatments on immature and mature 'Kensington' mangoes were examined. A hot water treatment of 47 degreesC fruit core temperature held for 15 min increased weight loss (50%), fruit softness (15%), disrupted starch hydrolysis and interacted with maturity to reduce the skin yellowness (40-51%) of early harvested fruit. Immature fruit were more susceptible to hot water treatment-induced skin scalding, starch layer and starch spot injuries and disease. Conditioning fruit at 40 degreesC for up to 16 h before hot water treatment accelerated fruit ripening, as reflected in higher total soluble solids and lower titratable acidity levels. As fruit maturity increased, the tolerance to hot water treatment-induced skin scalding and the retention of starch layers and starch spots increased and susceptibility to lenticel spotting decreased. A conditioning treatment of either 22 degrees or 40 degreesC before hot water treatment could prevent the appearance of cavities at all maturity levels. The 40 degreesC conditioning temperature was found to be more effective in increasing fruit heat tolerance than the 22 degreesC treatment; the longer the time of conditioning at 40 degreesC, the more effective the treatment (16 v. 4 h). For maximum fruit quality, particularly for export markets, it is recommended that mature fruit are selected and conditioned before hot water treatment to reduce the risk of heat damage.

Fate of swallowed interleukin 8 and TNF alpha and effect on the wistar rat gut

To evaluate the passage of cytokines through the gastrointestinal tract, we investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor α (TNFα), in vitro and in vivo, and their propensity to induce intestinal inflammation. We serially immuno-assayed IL-8 and TNFα solutions co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We gavaged IL-8, TNFα and marker into 15 Wistar rats, and measured their faecal cytokine concentrations by ELISA and histologically examined their guts. IL-8 immunoreactivity was extinguished by all pancreatin preparations after 1 h of incubation at 37 °C. TNFα concentration progressively fell from 1 to 4 h with all enzyme preparations. Buffer control samples maintained their cytokine concentrations throughout incubation. No IL-8 or TNFα was detected in any rat faecal pellets. There was no significant proinflammatory effect of the gavaged cytokines on rat intestine. IL-8 and TNFα in aqueous solution could well be fully digested in the CF gut when transit time is normal and exogenous enzymes are provided, although cytokines swallowed in viscous sputum may be protected from such digestion. Copyright © 2011 Elsevier B.V. All rights reserved

Effect of water temperature and oxygen levels on the diving behavior of two freshwater turtles: Rheodytes leukops and Emydura macquarii

Rheodytes leukops is a bimodally respiring turtle that extracts oxygen from the water chiefly via two enlarged cloacal bursae that are lined with multi-branching papillae. The diving performance of R. leukops was compared to that of Emydura macquarii, a turtle with a limited ability to acquire aquatic oxygen. The diving performance of the turtles was compared under aquatic anoxia (0 mmHg), hypoxia (80 mmHg) and normoxia (155 mmHg) at 15, 23, and 30degreesC. When averaged across all temperatures the dive duration of R. leukops more than doubled from 22.4 +/- 7.65 min under anoxia to 49.8 +/- 19.29 min under normoxic conditions. In contrast, aquatic oxygen level had no effect on the dive duration of E. macquarii. Dive times for both species were significantly longer at the cooler temperature, and the longest dive recorded for each species was 538 min and 166 min for R. leukops and E. macquarii, respectively. Both species displayed a pattern of many short dives punctuated by occasional long dives irrespective of temperature or oxygen regime. Rheodytes leukops, on average, spent significantly less time (42 +/- 2 sec) at the surface per surfacing event than did E. macquarii (106 +/- 20 sec); however, surface times for both species were not related to either water temperature or oxygen level.

Effect of maternal epidural analgesia on fetal intrapartum oxygen saturation

The use of maternal epidural analgesia in labor may be associated with nonreassuring fetal heart rate (FHR) patterns. Fetal oxygen saturation (FSpO(2)) monitoring may improve assessment of fetal well-being during this time. Mean FSpO(2) values were compared over seven 5-minute epochs: 5 minutes prior to an epidural event (combined insertion of epidural/top-up epidural analgesia and infusion pump bolus), to 30 minutes following the event, including possible effects of maternal position and FHR pattern on FSpO(2) values. Mean FSpO(2) values were significantly different between the 5 minutes prior (49.5%) versus 16-20 minutes (44.3%, p

Effect of the movement speed of resistance training exercises on sprint and strength performance in concurrently training elite junior sprinters

The aim of this study was to determine the effects of 7 weeks of high- and low-velocity resistance training on strength and sprint running performance in nine male elite junior sprint runners (age 19.0 +/- 1.4 years, best 100 m times 10.89 +/- 0.21 s; mean +/- s). The athletes continued their sprint training throughout the study, but their resistance training programme was replaced by one in which the movement velocities of hip extension and flexion, knee extension and flexion and squat exercises varied according to the loads lifted (i.e. 30-50% and 70-90% of 1-RM in the high- and low-velocity training groups, respectively). There were no between-group differences in hip flexion or extension torque produced at 1.05, 4.74 or 8.42 rad . s(-1), 20 m acceleration or 20 m 'flying' running times, or 1-RM squat lift strength either before or after training. This was despite significant improvements in 20 m acceleration time (P < 0.01), squat strength (P< 0.05), isokinetic hip flexion torque at 4.74 rad . s(-1) and hip extension torque at 1.05 and 4.74 rad . s(-1) for the athletes as a whole over the training period. Although velocity-specific strength adaptations have been shown to occur rapidly in untrained and non-concurrently training individuals, the present results suggest a lack of velocity-specific performance changes in elite concurrently training sprint runners performing a combination of traditional and semi-specific resistance training exercises.

Effect of varying levels of mental workload on startle eyeblink modulation

Previous research using punctuate reaction time and counting tasks has found that the startle eyeblink reflex is sensitive to attentional demands. The present experiment explored whether startle eyeblink is also modulated during a complex continuous task and is sensitive to different levels of mental workload. Participants (N=14) performed a visual horizontal tracking task either alone (single-task condition) or in combination with a visual gauge monitoring task (multiple-task condition) for three minutes. On some task trials, the startle eyeblink reflex was elicited by a noise burst. Results showed that startle eyeblink was attenuated during both tasks and that the attenuation was greater during the multiple-task condition than during the single-task condition. Subjective ratings, endogenous eyeblink rate, heart period, and heart period variability provided convergent validity of the workload manipulations. The findings suggest that the startle eyeblink is sensitive to the workload demands associated with a continuous visual task. The application of startle eyeblink modulation as a workload metric and the possibility that it may be diagnostic of workload demands in different stimulus modalities is discussed.

The effect of water, brine and ethanol flotation on the quality and shelf life of macadamia kernels 2. Kernel pieces

Raw macadamia kernel pieces were immersed in water (specific gravity 1.00 g/cm(3)), brine (SG 1.02 g/cm(3)) or ethanol solution (SG 0.97 g/cm(3)) for 30 or 60 s, then re-dried to below 1.5% moisture (wet basis) and stored under vacuum for 0, 4 and 12 months. Flotation in water had no effect on the quality or shelf life of the kernel pieces over 12 months storage, as measured by sensory evaluation of the kernels and chemical analysis of the kernel oil. Immersion in a salt solution caused unacceptable changes in quality during storage, increasing as storage time increased. Flotation in dilute ethanol also caused unacceptable quality changes during storage. Therefore, only flotation of macadamia kernel pieces in water can be recommended for commercial operations. Microbiological concerns with such a process still need to be addressed.