Prolonged cold storage of red blood cells by oxygen removal and additive usage

DOEpatents

Bitensky, M.W.; Yoshida, Tatsuro

1998-08-04

Prolonged cold storage of red blood cells by oxygen removal and additive usage. A cost-effective, 4 C storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. The improved in vivo survival and the preservation of adenosine triphosphate levels, along with reduction in hemolysis and membrane vesicle production of red blood cells stored at 4 C for prolonged periods of time, is achieved by reducing the oxygen level therein at the time of storage; in particular, by flushing the cells with an inert gas, and storing them in an aqueous solution which includes adenine, dextrose, mannitol, citrate ion, and dihydrogen phosphate ion, but no sodium chloride, in an oxygen-permeable container which is located in an oxygen-free environment containing oxygen-scavenging materials. 8 figs.

Prolonged cold storage of red blood cells by oxygen removal and additive usage

DOEpatents

Bitensky, Mark W.; Yoshida, Tatsuro

1998-01-01

Prolonged cold storage of red blood cells by oxygen removal and additive usage. A cost-effective, 4.degree. C. storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. The improved in vivo survival and the preservation of adenosine triphosphate levels, along with reduction in hemolysis and membrane vesicle production of red blood cells stored at 4.degree. C. for prolonged periods of time, is achieved by reducing the oxygen level therein at the time of storage; in particular, by flushing the cells with an inert gas, and storing them in an aqueous solution which includes adenine, dextrose, mannitol, citrate ion, and dihydrogen phosphate ion, but no sodium chloride, in an oxygen-permeable container which is located in an oxygen-free environment containing oxygen-scavenging materials.

Impact of Delayed Infusion Time in Umbilical Cord Blood Transplantation.

PubMed

Mitchell, Richard; Wagner, John E; Brunstein, Claudio; Cao, Qing; McKenna, David H; Verneris, Michael R

2017-05-01

In umbilical cord blood (UCB) transplantation, UCB units are typically thawed, washed, and infused into the patient as rapidly as possible. In some instances there is a delay in the time from the unit thaw and wash procedure to infusion into the patient. Therefore, we examined the effect of thaw duration time on engraftment outcomes in 567 patients undergoing UCB transplantation. With a range of 32 to 523 minutes, a prolonged thaw duration had no obvious effect on the incidence of neutrophil engraftment or time to recovery. This was true for recipients of single UCB transplantation (incidence: 97% versus 93%, P = .13; time to neutrophil recovery: 21 days versus 21 days, P = .32; and platelet recovery: 79% versus 78%, P = .48), and similar results were observed in double UCB transplantation (time to neutrophil engraftment: 20 days versus 19 days, P = .71). However, there was a trend toward better platelet recovery in recipients of double UCB transplants with prolonged thaw duration (HR, 1.28; P = .06). In conclusion, this study demonstrates prolonged thaw duration has no detrimental effect on engraftment after single or double UCB transplantation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Effect of Methysergide and X-irradiation on the Barbiturate Sleeping-time in Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varagić, V.; Stepanović, S.; Hajduković, S.

1962-10-01

Methysergide (1-methyl-D-lysergic acid butanolamide bimaleate), a highly potent and specific 5-hydroxytryptamine antagonist, if injected after irradiation, significantly depresses the proionging effect of x irradiation on the barbiturate sleeping-time in rats. Lysergic acid diethylamide did not show tius type of activity. 5-Hydroxytryptamine, when injected before irradiation, did not depress the typical response of the irradiated animals to barbiturates. When used after irradiation, 5-hydroxytryptamine caused a further prolongation of the barbiturate sleeping-time. Cysteamine, when injected before irradiation, depressed or blocked the prolonging effect of x irradiation on the barbiturate sleeping-time. When injected after irradiation, cysteamine was found to cause a further prolongationmore » of the barbiturate sleeping-time. The mechanisms of action of methysergide, 5-hydroxytryptamine, and cysteamine are briefly discussed. (auth)« less

Correlates of screen time among 8-19-year-old students in China.

PubMed

Ye, Sunyue; Chen, Lijian; Wang, Qineng; Li, Qinggong

2018-04-10

Previous studies have shown that prolonged time spent on screen-based sedentary behavior was significantly associated with lower health status in children, independent of physical activity levels. The study aimed to explore the individual and environmental correlates of screen time (ST) among 8-19-year-old students in China. The study surveyed ST using a self-administered questionnaire in Chinese students aged 8-19 years; 1063 participants were included in the final analysis. Individual and environmental correlates of ST were assessed using a mixed-effects model (for continuous outcome variables) and multiple logistic regression model (for binary outcome variables). Prolonged ST was observed in 14.7% of boys and 8.9% of girls. Of the ST, weekend and mobile phone/tablet use represented 80% and 40%, respectively. A positive relationship was observed between media accessibility and ST in both boys and girls (p < 0.05), whereas the presence of parents/others while using screens was a negative factor for longer ST (p < 0.05). Among the assessed correlates, access to a television (TV) in students' bedrooms was associated with prolonged total and weekend ST (p < 0.05 and p < 0.001, respectively). However, spending time on a mobile phone/tablet or a computer rather than viewing a TV, along with increased media accessibility, increased ST. These results indicate that greater media accessibility was positively associated and the presence of parents/others was negatively associated with prolonged ST in both Chinese boys and girls. Development of new and effective strategies against prolonged ST are required, especially for small screen device-based ST on weekends.

A review of ropinirole prolonged release in Parkinson’s disease

PubMed Central

Nashatizadeh, Muhammad M; Lyons, Kelly E; Pahwa, Rajesh

2009-01-01

Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson’s disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily “off” time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD. PMID:19503779

Surgical problems and complex procedures: issues for operative time in robotic totally endoscopic coronary artery bypass grafting.

PubMed

Wiedemann, Dominik; Bonaros, Nikolaos; Schachner, Thomas; Weidinger, Felix; Lehr, Eric J; Vesely, Mark; Bonatti, Johannes

2012-03-01

Robotically assisted totally endoscopic coronary artery bypass grafting (TECAB) is a viable option for closed chest coronary surgery, but it requires learning curves and longer operative times. This study evaluated the effect of extended operation times on the outcome of patients undergoing TECAB. From 2001 to 2009, 325 patients underwent TECAB with the da Vinci telemanipulation system. Correlations between operative times and preoperative, intraoperative, and early postoperative parameters were investigated. Receiver operating characteristic analysis was used to define the threshold of the procedure duration above which intensive care unit stay and ventilation time were prolonged. Demographic data, intraoperative and postoperative parameters, and survival data were compared. Patients with prolonged operative times more often underwent multivessel revascularization (P < .001) and beating-heart TECAB (P =.023). Other preoperative parameters were not associated with longer operative times. Incidences of technical difficulties and conversions (P < .001) were higher among patients with longer operative times. Prolonged intensive care unit stay, mechanical ventilation, hospital stay, and with requirement of blood products were associated with longer operative times. Receiver operating characteristic analysis showed operative times >445 minutes and >478 minutes to predict prolonged (>48 hours) intensive care unit stay and mechanical ventilation, respectively. Patients with procedures >478 minutes had longer hospital stays and higher perioperative morbidity and mortality. Kaplan-Meier analysis revealed decreased survival among patients with operative times >478 minutes. Multivessel revascularization and conversions lead to prolonged operative times in totally endoscopic coronary artery bypass grafting. Longer operative times significantly influence early postoperative and midterm outcomes. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Time-dependent behavioral, neurochemical, and metabolic dysregulation in female C57BL/6 mice caused by chronic high-fat diet intake

PubMed Central

Krishna, Saritha; Lin, Zhoumeng; de La Serre, Claire B.; Wagner, John J.; Harn, Donald H.; Pepples, Lacey M.; Djani, Dylan M.; Weber, Matthew T.; Srivastava, Leena; Filipov, Nikolay M.

2016-01-01

High-fat diet (HFD) induced obesity is associated not only with metabolic dysregulation, e.g., impaired glucose homeostasis and insulin sensitivity, but also with neurological dysfunction manifested with aberrant behavior and/or neurotransmitter imbalance. Most studies have examined HFD's effects predominantly in male subjects, either in the periphery or on the brain, in isolation and after a finite feeding period. In this study, we evaluated the time-course of selected metabolic, behavioral, and neurochemical effects of HFD intake in parallel and at multiple time points in female (C57BL/6) mice. Peripheral effects were evaluated at three feeding intervals (short: 5–6 weeks, long: 20–22 weeks, and prolonged: 33–36 weeks). Central effects were evaluated only after long and prolonged feeding durations; we have previously reported those effects after the short (5–6 weeks) feeding duration) [1]. Ongoing HFD feeding resulted in an obese phenotype characterized by increased visceral adiposity and, after prolonged HFD intake, an increase in liver and kidney weights. Peripherally, 5 weeks of HFD intake was sufficient to impair glucose tolerance significantly, with the deleterious effects of HFD being greater with prolonged intake. Similarly, 5 weeks of HFD consumption was sufficient to impair insulin sensitivity. However, sensitivity to insulin after prolonged HFD intake was not different between control, low-fat diet (LFD) and HFD-fed mice, most likely due to age-dependent decrease in insulin sensitivity in the LFD-fed mice. HFD intake also induced bi-phasic hepatic inflammation and it increased gut permeability. Behaviorally, prolonged intake of HFD caused mice to be hypoactive and bury fewer marbles in a marble burying task; the latter was associated with significantly impaired hippocampal serotonin homeostasis. Cognitive (short-term recognition memory) function of mice was unaffected by chronic HFD feeding. Considering our prior findings of short-term (5–6 weeks) HFD-induced central (hyperactivity/anxiety and altered ventral hippocampal neurochemistry) effects and our current results, it seems that in female mice some metabolic/inflammatory dysregulations caused by HFD, such as gut permeability, appear early and persist, whereas others, such as glucose intolerance, are exaggerated with continuous HFD feeding; behaviorally, prolonged HFD consumption mainly affects locomotor activity and anxiety-like responses, likely due to the advanced obesity phenotype; neurochemically, the serotonergic system appears to be most sensitive to continued HFD feeding. PMID:26852949

Time-dependent behavioral, neurochemical, and metabolic dysregulation in female C57BL/6 mice caused by chronic high-fat diet intake.

PubMed

Krishna, Saritha; Lin, Zhoumeng; de La Serre, Claire B; Wagner, John J; Harn, Donald H; Pepples, Lacey M; Djani, Dylan M; Weber, Matthew T; Srivastava, Leena; Filipov, Nikolay M

2016-04-01

High-fat diet (HFD) induced obesity is associated not only with metabolic dysregulation, e.g., impaired glucose homeostasis and insulin sensitivity, but also with neurological dysfunction manifested with aberrant behavior and/or neurotransmitter imbalance. Most studies have examined HFD's effects predominantly in male subjects, either in the periphery or on the brain, in isolation and after a finite feeding period. In this study, we evaluated the time-course of selected metabolic, behavioral, and neurochemical effects of HFD intake in parallel and at multiple time points in female (C57BL/6) mice. Peripheral effects were evaluated at three feeding intervals (short: 5-6 weeks, long: 20-22 weeks, and prolonged: 33-36 weeks). Central effects were evaluated only after long and prolonged feeding durations; we have previously reported those effects after the short (5-6 weeks) feeding duration. Ongoing HFD feeding resulted in an obese phenotype characterized by increased visceral adiposity and, after prolonged HFD intake, an increase in liver and kidney weights. Peripherally, 5 weeks of HFD intake was sufficient to impair glucose tolerance significantly, with the deleterious effects of HFD being greater with prolonged intake. Similarly, 5 weeks of HFD consumption was sufficient to impair insulin sensitivity. However, sensitivity to insulin after prolonged HFD intake was not different between control, low-fat diet (LFD) and HFD-fed mice, most likely due to age-dependent decrease in insulin sensitivity in the LFD-fed mice. HFD intake also induced bi-phasic hepatic inflammation and it increased gut permeability. Behaviorally, prolonged intake of HFD caused mice to be hypoactive and bury fewer marbles in a marble burying task; the latter was associated with significantly impaired hippocampal serotonin homeostasis. Cognitive (short-term recognition memory) function of mice was unaffected by chronic HFD feeding. Considering our prior findings of short-term (5-6 weeks) HFD-induced central (hyperactivity/anxiety and altered ventral hippocampal neurochemistry) effects and our current results, it seems that in female mice some metabolic/inflammatory dysregulations caused by HFD, such as gut permeability, appear early and persist, whereas others, such as glucose intolerance, are exaggerated with continuous HFD feeding; behaviorally, prolonged HFD consumption mainly affects locomotor activity and anxiety-like responses, likely due to the advanced obesity phenotype; neurochemically, the serotonergic system appears to be most sensitive to continued HFD feeding. Copyright © 2016 Elsevier Inc. All rights reserved.

Strategies to improve plasma half life time of peptide and protein drugs.

PubMed

Werle, M; Bernkop-Schnürch, A

2006-06-01

Due to the obvious advantages of long-acting peptide and protein drugs, strategies to prolong plasma half life time of such compounds are highly on demand. Short plasma half life times are commonly due to fast renal clearance as well as to enzymatic degradation occurring during systemic circulation. Modifications of the peptide/protein can lead to prolonged plasma half life times. By shortening the overall amino acid amount of somatostatin and replacing L: -analogue amino acids with D: -amino acids, plasma half life time of the derivate octreotide was 1.5 hours in comparison to only few minutes of somatostatin. A PEG(2,40 K) conjugate of INF-alpha-2b exhibited a 330-fold prolonged plasma half life time compared to the native protein. It was the aim of this review to provide an overview of possible strategies to prolong plasma half life time such as modification of N- and C-terminus or PEGylation as well as methods to evaluate the effectiveness of drug modifications. Furthermore, fundamental data about most important proteolytic enzymes of human blood, liver and kidney as well as their cleavage specificity and inhibitors for them are provided in order to predict enzymatic cleavage of peptide and protein drugs during systemic circulation.

Visual reaction times during prolonged angular acceleration parallel the subjective perception of rotation

NASA Technical Reports Server (NTRS)

Mattson, D. L.

1975-01-01

The effect of prolonged angular acceleration on choice reaction time to an accelerating visual stimulus was investigated, with 10 commercial airline pilots serving as subjects. The pattern of reaction times during and following acceleration was compared with the pattern of velocity estimates reported during identical trials. Both reaction times and velocity estimates increased at the onset of acceleration, declined prior to the termination of acceleration, and showed an aftereffect. These results are inconsistent with the torsion-pendulum theory of semicircular canal function and suggest that the vestibular adaptation is of central origin.

Computed tomography-guided screening of surfactant effect on blood circulation time of emulsions: application to the design of an emulsion formulation for paclitaxel.

PubMed

Lee, Eun-Hye; Hong, Soon-Seok; Kim, So Hee; Lee, Mi-Kyung; Lim, Joon Seok; Lim, Soo-Jeong

2014-08-01

In an effort to apply the imaging techniques currently used in disease diagnosis for monitoring the pharmacokinetics and biodisposition of particulate drug carriers, we sought to use computed tomography (CT) scanning methodology to investigate the impact of surfactant on the blood residence time of emulsions. We prepared the iodinated oil Lipiodol emulsions with different compositions of surfactants and investigated the impact of surfactant on the blood residence time of emulsions by CT scanning. The blood circulation time of emulsions was prolonged by including Tween 80 or DSPE-PEG (polyethylene glycol 2000) in emulsions. Tween 80 was less effective than DSPE-PEG in terms of prolongation effect, but the blood circulating time of emulsions was prolonged in a Tween 80 content-dependent manner. As a proof-of-concept demonstration of the usefulness of CT-guided screening in the process of formulating drugs that need to be loaded in emulsions, paclitaxel was loaded in emulsions prepared with 87 or 65% Tween 80-containing surfactant mixtures. A pharmacokinetics study showed that paclitaxel loaded in 87% Tween 80 emulsions circulated longer in the bloodstream compared to those in 65% Tween 80 emulsions, as predicted by CT imaging. CT-visible, Lipiodol emulsions enabled the simple evaluation of surfactant composition effects on the biodisposition of emulsions.

Gluteus medius coactivation response in field hockey players with and without low back pain.

PubMed

Bussey, Melanie D; Kennedy, James E; Kennedy, Gavin

2016-01-01

To examine the effect of prolonged standing on gluteus medius coactivation and to observe whether the changes in gluteus medius coactivation over time were related to the development of low back pain in elite female field hockey players. Prospective cohort design. Participants were 39 elite female field hockey players (14 with a history of low back pain). Before the prolonged stand, maximal hip abduction strength, side bridge hold endurance and hip abduction range of motion were measured bilaterally. Surface electromyography was collected from the gluteus medius for coactivation analysis during a prolonged stand for 70 min. Low back pain was rated every 10 min on a visual analogue scale. Fourteen of 39 participants developed low back pain. The Time effect was significant for gluteus medius coactivation response (p = 0.003) and visual analogue scale score (p < 0.001). There were no significant group × time interactions. Yet athletes who developed pain had higher coactivation for the majority of the stand task. While female field hockey players have high agonist-antagonist coactivation patterns during prolonged standing, stand task is a useful tool to predict low back pain occurrence in players with and without history of pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evidence of Health Risks Associated with Prolonged Standing at Work and Intervention Effectiveness

PubMed Central

Waters, Thomas R.; Dick, Robert B.

2015-01-01

Purpose Prolonged standing at work has been shown to be associated with a number of potentially serious health outcomes, such as lower back and leg pain, cardiovascular problems, fatigue, discomfort, and pregnancy related health outcomes. Recent studies have been conducted examining the relationship between these health outcomes and the amount of time spent standing while on the job. The purpose of this article was to provide a review of the health risks and interventions for workers and employers that are involved in occupations requiring prolonged standing. A brief review of recommendations by governmental and professional organizations for hours of prolonged standing is also included. Findings Based on our review of the literature, there seems to be ample evidence showing that prolonged standing at work leads to adverse health outcomes. Review of the literature also supports the conclusion that certain interventions are effective in reducing the hazards associated with prolonged standing. Suggested interventions include the use of floor mats, sit-stand workstations/chairs, shoes, shoe inserts and hosiery or stockings. Studies could be improved by using more precise definitions of prolonged standing (e.g., duration, movement restrictions, and type of work), better measurement of the health outcomes and more rigorous study protocols. Conclusion and Clinical Relevance Use of interventions and following suggested guidelines on hours of standing from governmental and professional organizations should reduce the health risks from prolonged standing. PMID:25041875

Effects of five sulphonamides on duckweed (Lemna minor) after prolonged exposure time and their dependency on photoradiation.

PubMed

Białk-Bielińska, Anna; Matzke, Marianne; Caban, Magda; Stolte, Stefan; Kumirska, Jolanta; Stepnowski, Piotr

2018-03-15

Sulphonamides (SAs) are one of the most commonly used veterinary drugs and therefore their residues are regularly found in the environment. So far scientific attention has mostly been paid to the evaluation of their acute ecotoxicological effects with data on long-term effects for non-target organisms still largely missing. Therefore, the main aim of this study was to evaluate the potential toxicities of five sulphonamides to duckweed (Lemna minor) after prolonged exposure time (14days). To elucidate whether their phytotoxic effects result from potential photodegradation products, the toxicity of standard solutions of selected sulphonamides was also investigated in a standard 7-day test but after irradiation (by keeping them under the test conditions) for the selected time (after 7 and 14days). The ecotoxicological tests were accompanied by chemical analyses to be able to link the observed effects to the concentrations and nature of the exposed compounds. The results showed a shift in the toxicity of SAs: a strong decrease in toxicity for the two most toxic sulphonamides (sulphamethoxazole and sulphadimethoxine) and a slight increase in toxicity for three other SAs (sulphadimidine, sulphathiazole, sulphamerazine) in the prolonged test. However, a decrease in the toxicity and concentration of all the SAs was observed when stock solutions were irradiated prior to the toxicity experiment, which suggests that the observed effects towards L. minor of five SAs in the prolonged test cannot be directly associated with the degradation of these compounds under the test conditions but with their different mode of toxic action towards these organisms. Copyright © 2017 Elsevier B.V. All rights reserved.

How Does Definition of Minimum Break Length Affect Objective Measures of Sitting Outcomes Among Office Workers?

PubMed

Kloster, Stine; Danquah, Ida Høgstedt; Holtermann, Andreas; Aadahl, Mette; Tolstrup, Janne Schurmann

2017-01-01

Harmful health effects associated with sedentary behavior may be attenuated by breaking up long periods of sitting by standing or walking. However, studies assess interruptions in sitting time differently, making comparisons between studies difficult. It has not previously been described how the definition of minimum break duration affects sitting outcomes. Therefore, the aim was to address how definitions of break length affect total sitting time, number of sit-to-stand transitions, prolonged sitting periods and time accumulated in prolonged sitting periods among office workers. Data were collected from 317 office workers. Thigh position was assessed with an ActiGraph GT3X+ fixed on the right thigh. Data were exported with varying bout length of breaks. Afterward, sitting outcomes were calculated for the respective break lengths. Absolute numbers of sit-to-stand transitions decreased, and number of prolonged sitting periods and total time accumulated in prolonged sitting periods increased, with increasing minimum break length. Total sitting time was not influenced by varying break length. The definition of minimum break length influenced the sitting outcomes with the exception of total sitting time. A standard definition of break length is needed for comparison and interpretation of studies in the evolving research field of sedentary behavior.

Circadian, endocrine, and metabolic effects of prolonged bedrest: Two 56-day bedrest studies

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Winget, C. M.; Leach, C. S.; Rambaut, P. C.

1974-01-01

Two bedrest studies of 56 days each have been conducted to evaluate the effects of prolonged bedrest on circadian synchrony and endocrine and metabolic function. Measurements included the pituitary-adrenal, thyroid, parathyroid, insulin-glucose-growth hormones, catecholamine excretion, body temperature, and heart rate. The results indicated that a rigorous regimen of exercise did not prevent the endocrine and metabolic effects of prolonged bedrest. Changes in circadian, endocrine, and metabolic functions in bedrest appear to be due to changes in hydrostatic pressure and lack of postural cues rather than to inactivity, confinement, or the bleeding schedule. Prolonged bedrest, particularly beyond 24 days, resulted in rhythm desynchronization in spite of well regulated light/dark cycles, temperature, humidity, activity, and meal times and meal composition and in increased lability of all endocrine parameter measured. It also resulted in an apparent insensitivity of the glucose response to insulin, of cortisol secretion to ACTH, and of growth hormone secretion to hypoglycemia.

Antihypoxic activities of Eryngium caucasicum and Urtica dioica.

PubMed

Khalili, M; Dehdar, T; Hamedi, F; Ebrahimzadeh, M A; Karami, M

2015-09-01

Urtica dioica and Eryngium spp. have been used in traditional medicine for many years. In spite of many works, nothing is known about their protective effect against hypoxia-induced lethality. Protective effects of U. dioica (UD) aerial parts and E. caucasicum (EC) inflorescence against hypoxia-induced lethality in mice were evaluated by three experimental models of hypoxia, asphyctic, haemic and circulatory. Statistically significant protective activities were established in some doses of extracts in three models. Antihypoxic activity was especially pronounced in polyphenol fractions in asphyctic model. EC polyphenol fraction at 400 mg/kg prolonged survival time (48.80 ± 4.86, p < 0.001) which was comparable with that of phenytoin (p > 0.05). It was the most effective extract in circulatory model, too. It prolonged survival time significantly respect to control group (p < 0.001). UD extracts protected the mice but the response was not dose-dependent. In haemic model, extracts of EP significantly and dose dependently prolonged survival time as compared to control group (p < 0.001). At 600 mg/kg, EP was the most effective one, being capable of keeping the mice alive for 12.71 ± 0.75 min. Only the concentration of 300 mg/kg of UD was effective (p < 0.001). Extracts showed remarkable antihypoxic effects. Pharmacological effects may be attributed to the presence of polyphenols in the extracts.

Survival time of dogs with splenic hemangiosarcoma treated by splenectomy with or without adjuvant chemotherapy: 208 cases (2001-2012).

PubMed

Wendelburg, Kristin M; Price, Lori Lyn; Burgess, Kristine E; Lyons, Jeremiah A; Lew, Felicia H; Berg, John

2015-08-15

To determine survival time for dogs with splenic hemangiosarcoma treated with splenectomy alone, identify potential prognostic factors, and evaluate the efficacy of adjuvant chemotherapy. Retrospective case series. 208 dogs. Medical records were reviewed, long-term follow-up information was obtained, and survival data were analyzed statistically. 154 dogs were treated with surgery alone, and 54 were treated with surgery and chemotherapy. Twenty-eight dogs received conventional chemotherapy, 13 received cyclophosphamide-based metronomic chemotherapy, and 13 received both conventional and metronomic chemotherapy. Median survival time of dogs treated with splenectomy alone was 1.6 months. Clinical stage was the only prognostic factor significantly associated with survival time. When the entire follow-up period was considered, there was no significant difference in survival time between dogs treated with surgery alone and dogs treated with surgery and chemotherapy. However, during the first 4 months of follow-up, after adjusting for the effects of clinical stage, survival time was significantly prolonged among dogs receiving any type of chemotherapy (hazard ratio, 0.6) and among dogs receiving both conventional and metronomic chemotherapy (hazard ratio, 0.4). Clinical stage was strongly associated with prognosis for dogs with splenic hemangiosarcoma. Chemotherapy was effective in prolonging survival time during the early portion of the follow-up period. Combinations of doxorubicin-based conventional protocols and cyclophosphamide-based metronomic protocols appeared to be more effective than either type of chemotherapy alone, but prolongations in survival time resulting from current protocols were modest.

Effect of choline supplementation on fatigue in trained cyclists.

PubMed

Spector, S A; Jackman, M R; Sabounjian, L A; Sakkas, C; Landers, D M; Willis, W T

1995-05-01

The availability of choline, the precurser of the neurotransmitter, acetylcholine, in the diet is sufficient to provide the body's requirements under normal conditions. However, preliminary evidence indicates that depletion of choline may limit performance, while oral supplementation may delay fatigue during prolonged efforts. A double-blind cross-over design was used to determine the relationship between plasma choline and fatigue during supramaximal brief and submaximal prolonged activities. Twenty male cyclists (ages 23-29) with maximal aerobic power (VO2max) between 58 and 81 ml.min-1.kg-1 were randomly divided into BRIEF (N = 10) and PROLONGED (N = 10) groups. One hour after drinking a beverage with or without choline bitartrate (2.43 g), cyclists began riding at a power output equivalent to approximately 150% (BRIEF) and 70% (PROLONGED) of VO2max at a cadence of 80-90 rpm. Time to exhaustion, indirect calorimetry and serum choline, lactate, and glucose were measured. Increases in choline levels of 37 and 52% were seen within one hour of ingestion for BRIEF and PROLONGED groups, respectively. Neither group depleted choline during exercise under the choline or placebo conditions. Fatigue times and work performed under either test condition for the BRIEF or PROLONGED groups were similar. Consequently, trained cyclists do not deplete choline during supramaximal brief or prolonged submaximal exercise, nor do they benefit from choline supplementation to delay fatigue under these conditions.

Transient impact of prolonged versus repetitive stretch on hand motor control in chronic stroke.

PubMed

Triandafilou, Kristen M; Ochoa, Jose; Kang, Xuan; Fischer, Heidi C; Stoykov, Mary Ellen; Kamper, Derek G

2011-01-01

The purpose of this study was to investigate the influence of prolonged and repetitive passive range of motion (PROM) stretching of the fingers on hand function in stroke survivors. Fifteen chronic stroke survivors with moderate to severe hand impairment took part in the study. Participants underwent 3 experimental sessions consisting of 30 minutes of rest, prolonged, or repetitive stretching of the finger flexor muscles by a powered glove orthosis (X-Glove). Outcome measures, comprised of 3 selected tasks from the Graded Wolf Motor Function Test (GWMFT), grip strength, lateral pinch strength, and grip relaxation time, were recorded at the start and end of each session. Change in outcome score for each session was used for analysis. Data suggested a trend for improvement following stretching, especially for the repetitive PROM case. For one GWMFT task (lift washcloth), the effect of stretching condition on performance time approached a statistical significance (P = .015), with repetitive PROM stretching producing the greatest mean reduction. Similarly, repetitive stretching led to a 12% ± 16% increase in grip strength, although this change was not statistically different across groups (P = .356); and grip termination time was reduced, albeit non-significantly, by 66% ± 133%. Repetitive PROM stretching exhibited trends to be more effective than prolonged stretching for improving hand motor control. Although the results were highly variable and the effects are undoubtedly transient, an extended period of repetitive PROM stretching may prove advantageous prior to hand therapy sessions to maximize treatment.

Effect of levothyroxine on prolonged nocturnal sleep time and excessive daytime somnolence in patients with idiopathic hypersomnia.

PubMed

Shinno, Hideto; Ishikawa, Ichiro; Yamanaka, Mami; Usui, Ai; Danjo, Sonoko; Inami, Yasushi; Horiguchi, Jun; Nakamura, Yu

2011-06-01

This study aims to examine the effect of levothyroxine, a thyroid hormone, on a prolonged nocturnal sleep and excessive daytime somnolence (EDS) in patients with idiopathic hypersomnia. In a prospective, open-label study, nine patients were enrolled. All subjects met criteria for idiopathic hypersomnia with long sleep time defined by the International Classification of Sleep Disorders, 2nd edition (ICSD-2). Subjects with sleep apnea syndrome, obesity or hypothyroidism were excluded. Sleep architecture and subjective daytime somnolence were estimated by polysomnography (PSG) and Epworth Sleepiness Scale (ESS), respectively. After baseline examinations, levothyroxine (25μg/day) was orally administered every day. Mean total sleep time, ESS score at baseline were compared with those after treatment (2, 4 and 8 weeks). Mean age of participants was 23.8±13.7 years old. At baseline, mean total sleep time (hours) and ESS score were 12.9±0.3 and 17.8±1.4, respectively. Mean total sleep times after treatment were 9.1±0.7 and 8.5±1.0h at 4 and 8 treatment weeks, respectively. Mean ESS scores were 8.8±2.3 and 7.4±2.8 at 4 and 8 treatment weeks, respectively. One patient dropped out at the 2nd week due to poor effect. No adverse effects were noted. After treatment with levothyroxine for over 4 weeks, prolonged sleep time and EDS were improved. Levothyroxine was effective for hypersomnia and well tolerated. Copyright © 2011 Elsevier B.V. All rights reserved.

Associations between change in sedentary behavior and outcome in standard behavioral weight loss treatment.

PubMed

Kerrigan, Stephanie G; Call, Christine; Schaumberg, Katherine; Forman, Evan; Butryn, Meghan L

2018-03-01

Sedentary behavior, particularly in prolonged periods, is an important determinant of health. Little research exploring changes in sedentary behavior during behavioral weight loss programs exists. This study evaluated the magnitude of changes in total and prolonged sedentary behavior and how these changes related to changes in weight and cardiovascular outcomes during a behavioral weight loss program. Participants (n = 450) in two lifestyle modification programs underwent assessments of sedentary behavior (by accelerometry), weight, waist circumference, blood pressure, and resting heart rate at baseline and after 6 months of treatment. Sedentary behavior was defined as both total and prolonged (≥30 continuous minutes) sedentary minutes/day. Reductions in total and prolonged sedentary time were significant and were accounted for by increases in moderate-to-vigorous physical activity (MVPA). Only changes in MVPA significantly predicted change in weight when entered into a model simultaneously with changes in sedentary behavior. Changes in total and prolonged sedentary time were not associated with changes in waist circumference, heart rate, or blood pressure. Change in sedentary time was not independently associated with change in health outcomes during a behavioral weight loss treatment. High variability in changes in sedentary time indicate that individual differences may be important to examine. Reducing sedentary time may not be powerful enough to impact these health outcomes above the effects of other changes made during these programs; alternatively, it may be that increasing focus in treatment on reducing sedentary time may engender greater decreases in sedentariness, which could lead to better health outcomes.

Effect of breaking up sedentary time with callisthenics on endothelial function.

PubMed

Carter, Sophie E; Gladwell, Valerie F

2017-08-01

Periods of prolonged sitting impairs endothelial function in lower limb conduit arteries, which is attenuated with physical activity breaks. The effect of activity breaks on upper limb arteries has not been examined. This study assessed changes in brachial artery endothelial function following either a prolonged sitting period or breaking up this sedentary time by performing sets of callisthenics exercises. Ten healthy participants (6 men) completed 2 conditions in a counterbalanced order: (a) 1-h 26-min sitting, or (b) breaking up this period every 20 min by performing a set of 5 callisthenics exercises. Brachial artery endothelial function was assessed via ultrasound using the flow-mediated dilation (FMD) technique prior to and following each condition, while brachial shear rate (SR) was acquired after each set of callisthenics. There was no significant change in FMD over time (P = 0.09) or between conditions (P = 0.12). Compared to sitting, brachial SR increased following each set of callisthenics, with a significant difference after the third break (Sit: 33.94 ± 12.79 s -1 ; Callisthenics: 57.16 ± 30.48 s -1 , P = 0.02). Alterations in SR in the upper limbs suggest callisthenics may be an effective intervention to break up sedentary time and attenuate the potentially deleterious effects of prolonged sitting on cardiovascular health.

The impact of work-related and personal resources on older workers' fatigue, work enjoyment and retirement intentions over time.

PubMed

Stynen, Dave; Jansen, Nicole W H; Kant, IJmert

2017-12-01

This study aims to examine the impact of work-related and personal resources on older workers' retirement intentions by studying the pathways (fatigue and work enjoyment) from resources to retirement intentions, the buffering role of resources for psychological job demands, in a cross-sectional and longitudinal timeframe. Longitudinal results on a subsample of full-time, older workers (n = 1642) from the Maastricht Cohort Study suggest that over four years of follow-up personal resources like personal mastery and perceived health related to less (prolonged) fatigue and more work enjoyment. Personal mastery also related to later retirement intentions. A work-related resource like decision authority related to less prolonged fatigue. (Prolonged) fatigue related to earlier retirement intentions, suggesting that fatigue may be a pathway to early retirement. Finally, little evidence was found for effect modification by resources. This prospective study indicates that work-related and personal resources may be useful for prolonging working careers. Practitioner Summary: To date, the impact of work-related and personal resources on older workers' retirement intentions is rarely studied. As this prospective study shows that resources may impact older workers' (prolonged) fatigue, work enjoyment and retirement intentions, the monitoring and fostering of resources is of importance for prolonging their working careers.

Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

PubMed

Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen

2016-06-01

Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (-7%, P = 0.009; -7.8%, P < 0.0001; -6.9%, P < 0.0001; and -4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

Prolonged Screen Viewing Times and Sociodemographic Factors among Pregnant Women: A Cross-Sectional Survey in China

PubMed Central

Liu, Dengyuan; Rao, Yunshuang; Zeng, Huan; Zhang, Fan; Wang, Lu; Xie, Yaojie; Sharma, Manoj; Zhao, Yong

2018-01-01

Objectives: This study aimed to assess the prevalence of prolonged television, computer, and mobile phone viewing times and examined related sociodemographic factors among Chinese pregnant women. Methods: In this study, a cross-sectional survey was implemented among 2400 Chinese pregnant women in 16 hospitals of 5 provinces from June to August in 2015, and the response rate of 97.76%. We excluded women with serious complications and cognitive disorders. The women were asked about their television, computer, and mobile phone viewing during pregnancy. Prolonged television watching or computer viewing was defined as spending more than two hours on television or computer viewing per day. Prolonged mobile phone viewing was watching more than one hour on mobile phone per day. Results: Among 2345 pregnant women, about 25.1% reported prolonged television viewing, 20.6% reported prolonged computer viewing, and 62.6% reported prolonged mobile phone viewing. Pregnant women with long mobile phone viewing times were likely have long TV (Estimate = 0.080, Standard Error (SE) = 0.016, p < 0.001) and computer viewing times (Estimate = 0.053, SE = 0.022, p = 0.015). Pregnant women with long TV (Estimate = 0.134, SE = 0.027, p < 0.001) and long computer viewing times (Estimate = 0.049, SE = 0.020, p = 0.015) were likely have long mobile phone viewing times. Pregnant women with long TV viewing times were less likely to have long computer viewing times (Estimate = −0.032, SE = 0.015, p = 0.035), and pregnant women with long computer viewing times were less likely have long TV viewing times (Estimate = −0.059, SE = 0.028, p = 0.035). Pregnant women in their second pregnancy had lower prolonged computer viewing times than those in their first pregnancy (Odds Ratio (OR) 0.56, 95% Confidence Interval (CI) 0.42–0.74). Pregnant women in their second pregnancy were more likely have longer prolonged mobile phone viewing times than those in their first pregnancy (OR 1.25, 95% CI 1.01–1.55). Conclusions: The high prevalence rate of prolonged TV, computer, and mobile phone viewing times was common for pregnant women in their first and second pregnancy. This study preliminarily explored the relationship between sociodemographic factors and prolonged screen time to provide some indication for future interventions related to decreasing screen-viewing times during pregnancy in China. PMID:29495439

[Beta lactam antibiotics and the question of dose regimen for severe infection. Prolonged infusion theoretically appealing--yet no evidence of clinical benefit].

PubMed

Leander, Gunilla; Eliasson, Erik; Hanberger, Håkan; Giske, Christian

2015-03-24

Patients with severe sepsis/septic shock have a high mortality. Beta-lactam antibiotics are normally first line treatment. This antimicrobial class has been associated with time-dependent efficacy. It is therefore plausible that administration as prolonged infusion will increase the therapeutic effect, as compared to short term bolus injections, which is the most common practice today. We have reviewed 14 randomized controlled studies to investigate whether prolonged infusion provides lower mortality and/or increased clinical cure. In summary, convincing advantages with prolonged infusion could not be found, however randomized studies are heterogeneous, and it cannot be excluded that some subgroups of critically ill patients could benefit from such treatment.

Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

PubMed

Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

2018-01-01

Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

Synthesis and antiplatelet effects of the new antithrombotic agent aspalatone with low ulcerogenicity.

PubMed

Han, B H; Suh, D Y; Yang, H O; Park, Y H; Kang, Y H; Kim, Y C

1994-10-01

A new compound, aspalatone (acetylsalicylic acid maltol ester), was synthesized by esterification of acetylsalicylic acid (ASA) and maltol, an antioxidant, and studied for its bleeding time prolongation effect in rats, for its antiplatelet aggregation activity in vitro and ex vivo in rats, and for its antithrombotic activity in vivo using the mouse thromboembolism test. Aspalatone treatment (15 mg/kg p.o.) for 10 days prolonged bleeding time by 57% (p < 0.005) in Sprague-Dawley rats vs control, while ASA treatment (15 mg/kg p.o.) prolonged by 44%. At the low dose of 15 mg/kg p.o. at least 8 days of treatment were necessary for aspalatone and ASA to prolong the bleeding time significantly. On the other hand, salicylic acid maltol ester which lacks the acetyl group did not significantly affect bleeding time at a dose of 15 mg/kg. Aspalatone produced a potent inhibition of collagen-induced platelet aggregation in vitro with IC50 of 1.8 x 10(-4) mol/l, but, similar to ASA, did not significantly inhibit ADP-induced aggregation. The ability of oral aspalatone to inhibit platelet aggregation in rats ex vivo was compared with other reference antiplatelet drugs. Relative potency was ASA > dipyridamole approximately equal to aspalatone > ticlopidine. A single dose of aspalatone potently prevented death due to collagen-induced platelet aggregation in mice in vivo with ED50 value of 32 mg/kg p.o., but failed to prevent death due to ADP-induced platelet aggregation. When given for 10 days, aspalatone prevented collagen-induced death by 90% (p < 0.001) at 20 mg/kg, and this antithrombotic effect lasted after 4 days of wash-out period.(ABSTRACT TRUNCATED AT 250 WORDS)

Providing a diet containing only maintenance levels of energy and protein during the latter stages of pregnancy resulted in a prolonged delivery time during parturition in rats.

PubMed

Tanaka, Y; Kadokawa, H

2012-01-01

In mammals, a prolonged delivery time during parturition is dangerous for both mother and fetus, although the mechanisms that prolong delivery are unclear. To investigate whether nutrition affects delivery time, we administered two feeds containing maintenance (L-feed) or higher (H-feed) levels of energy and protein at different points during the latter half of pregnancy and compared the effects of the various treatments on delivery time in rats. After the rats had been maintained on the L-feed and then copulated on pro-oestrus (Day 0), pregnant females were randomly allocated to one of three groups: (1) the no-improvement group, which was fed L-feed throughout gestation; (2) the early group, which was fed L-feed until Day 11 of gestation and then switched to H-feed; and (3) the late group, which was fed L-feed until Day 16 of gestation and then switched to H-feed. There was no significant difference in the number of pups among the three groups. However, delivery time was significantly longer in the no-improvement group (73.7±5.2 min) than the early (46.9±5.6 min) and late (55.4±5.5 min) groups. Consuming a maintenance diet during the latter half of pregnancy resulted in a prolonged delivery time.

Development of prolonged standing strain index to quantify risk levels of standing jobs.

PubMed

Halim, Isa; Omar, Abdul Rahman

2012-01-01

Many occupations in industry such as metal stamping workers, electronics parts assembly operators, automotive industry welders, and lathe operators require working in a standing posture for a long time. Prolonged standing can contribute to discomfort and muscle fatigue particularly in the back and legs. This study developed the prolonged standing strain index (PSSI) to quantify the risk levels caused by standing jobs, and proposed recommendations to minimize the risk levels. Risk factors associated with standing jobs, such as working posture, muscles activity, standing duration, holding time, whole-body vibration, and indoor air quality, were the basis for developing the PSSI. All risk factors were assigned multipliers, and the PSSI was the product of those multipliers. Recommendations for improvement are based on the PSSI; however, extensive studies are required to validate their effectiveness. multipliers, and the PSSI was the product of those multipliers. Recommendations for improvement are based on the PSSI; however, extensive studies are required to validate their effectiveness.

Effect of prolonged incubation time on results of the QuantiFERON TB gold in-tube assay for diagnosis of latent tuberculosis infection.

PubMed

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo; Yim, Jae-Joon

2013-09-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.

Effect of Prolonged Incubation Time on Results of the QuantiFERON TB Gold In-Tube Assay for Diagnosis of Latent Tuberculosis Infection

PubMed Central

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo

2013-01-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results. PMID:23825190

A detailed description of the short-term musculoskeletal and cognitive effects of prolonged standing for office computer work.

PubMed

Baker, Richelle; Coenen, Pieter; Howie, Erin; Lee, Jeremy; Williamson, Ann; Straker, Leon

2018-07-01

Due to concerns about excessive sedentary exposure for office workers, alternate work positions such as standing are being trialled. However, prolonged standing may have health and productivity impacts, which this study assessed. Twenty adult participants undertook two hours of laboratory-based standing computer work to investigate changes in discomfort and cognitive function, along with muscle fatigue, movement, lower limb swelling and mental state. Over time, discomfort increased in all body areas (total body IRR [95% confidence interval]: 1.47[1.36-1.59]). Sustained attention reaction time (β = 18.25[8.00-28.51]) deteriorated, while creative problem solving improved (β = 0.89[0.29-1.49]). There was no change in erector spinae, rectus femoris, biceps femoris or tibialis anterior muscle fatigue; low back angle changed towards less  lordosis, pelvis movement increased, lower limb swelling increased and mental state decreased. Body discomfort was positively correlated with mental state. The observed changes suggest replacing office work sitting with standing should be done with caution. Practitioner Summary: Standing is being used to replace sitting by office workers; however, there are health risks associated with prolonged standing. In a laboratory study involving 2 h prolonged standing discomfort increased (all body areas), reaction time and mental state deteriorated while creative problem-solving improved. Prolonged standing should be undertaken with caution.

Crataegus extract prolongs action potential duration in guinea-pig papillary muscle.

PubMed

Müller, A; Linke, W; Zhao, Y; Klaus, W

1996-11-01

Crataegus extract is used in cardiology for the treatment of moderate heart failure (NYHA II). Recently it was shown that Crataegus extract prolongs the refractory period in isolated perfused guinea pig hearts. In order to find out what mechanism is responsible for this prolongation of refractory period, we investigated the effects of Crataegus extract (LI 132) on the action potential of guinea pig papillary muscle with the help of conventional microelectrode techniques. Crataegus extract, when put in a concentration (10 mg/l) capable of inducing an inotropic effect of about 20%, significantly increased action potential duration at all investigated levels of repolarisation. Maximum prolongation was 8.5±2.3 ms, 12.5±2.6 ms and 11.7±2.9 ms at 20%, 50% and 90% repolarisation, respectively (control APD(90): 172±4 ms). Experiments on the time course of recovery of the maximum upstroke velocity (V(max)) of the action potential revealed that Crataegus extract increased the time constant of recovery of V(max) from 8.80±2.33 ms to 22.60±5.77 ms, indicating a weak Class I-like antiarrhythmic action. In addition, we observed a small reduction in V(max). In summary, our results show that Crataegus extract prolongs action potential duration and delays recovery of V(max). We, therefore, suggest that Crataegus extract possesses certain antiarrhythmic properties. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, Katie A.; Woodley, Christa M.; Seaburg, Adam

While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na +, K +, Ca 2+, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were nomore » mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na +, Ca 2+, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na +, Ca 2+, K +, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.« less

Determining delayed admission to intensive care unit for mechanically ventilated patients in the emergency department.

PubMed

Hung, Shih-Chiang; Kung, Chia-Te; Hung, Chih-Wei; Liu, Ber-Ming; Liu, Jien-Wei; Chew, Ghee; Chuang, Hung-Yi; Lee, Wen-Huei; Lee, Tzu-Chi

2014-08-23

The adverse effects of delayed admission to the intensive care unit (ICU) have been recognized in previous studies. However, the definitions of delayed admission varies across studies. This study proposed a model to define "delayed admission", and explored the effect of ICU-waiting time on patients' outcome. This retrospective cohort study included non-traumatic adult patients on mechanical ventilation in the emergency department (ED), from July 2009 to June 2010. The primary outcomes measures were 21-ventilator-day mortality and prolonged hospital stays (over 30 days). Models of Cox regression and logistic regression were used for multivariate analysis. The non-delayed ICU-waiting was defined as a period in which the time effect on mortality was not statistically significant in a Cox regression model. To identify a suitable cut-off point between "delayed" and "non-delayed", subsets from the overall data were made based on ICU-waiting time and the hazard ratio of ICU-waiting hour in each subset was iteratively calculated. The cut-off time was then used to evaluate the impact of delayed ICU admission on mortality and prolonged length of hospital stay. The final analysis included 1,242 patients. The time effect on mortality emerged after 4 hours, thus we deduced ICU-waiting time in ED > 4 hours as delayed. By logistic regression analysis, delayed ICU admission affected the outcomes of 21 ventilator-days mortality and prolonged hospital stay, with odds ratio of 1.41 (95% confidence interval, 1.05 to 1.89) and 1.56 (95% confidence interval, 1.07 to 2.27) respectively. For patients on mechanical ventilation at the ED, delayed ICU admission is associated with higher probability of mortality and additional resource expenditure. A benchmark waiting time of no more than 4 hours for ICU admission is recommended.

Lower limb kinematics of male and female soccer players during a self-selected cutting maneuver: Effects of prolonged activity.

PubMed

McGovern, Andrew; Dude, Christopher; Munkley, Daniel; Martin, Thomas; Wallace, David; Feinn, Richard; Dione, Donald; Garbalosa, Juan C

2015-12-01

Despite the recent emphasis on injury prevention, anterior cruciate ligament (ACL) injury rates remain high. This study aimed to ascertain the effects of prolonged activity on lower limb kinematics during a self-selected cutting maneuver. Angular kinematics were recorded during an agility test performed until the completion time was greater than the mean plus one SD of baseline trials. Cut type was identified and the hip and knee angles at 33 ms post heel strike were determined. A linear mixed effects model assessed the effects of cut type, gender, and activity status on the hip and knee angles. Males performed sidestep cuts more frequently than females. Females increased the incidence of sidestep cuts after prolonged activity. At the hip, a gender-cut type interaction existed for the transverse (p=0.001) and sagittal (p=0.11) planes. Females showed more internal rotation during sidestep and more external rotation and less flexion during crossover cuts. For the frontal plane, a gender-activity status interaction (p = 0.032) was due to no change within females but greater hip adduction during prolonged activity within males. With prolonged activity, both genders displayed less hip (p=0.29) and knee (p=0.009) flexion and more knee (p=0.001) adduction. Females displayed less hip and knee flexion than men (p=0.001). Sidestep may be more risky than crossover cuts. Both genders place themselves in at-risk postures with prolonged activity due to less hip and knee flexion. Copyright © 2015 Elsevier B.V. All rights reserved.

Matrix tablets for sustained release of repaglinide: Preparation, pharmacokinetics and hypoglycemic activity in beagle dogs.

PubMed

He, Wei; Wu, Mengmeng; Huang, Shiqing; Yin, Lifang

2015-01-15

Repaglinide (RG) is an efficient antihyperglycemic drug; however, due to its short half-life, patients are required to take the marketed products several times a day, which compromises the therapeutic effects. The present study was conducted to develop a hydrophilic sustained release matrix tablet for RG with the aims of prolonging its action time, reducing the required administration times and side effects and improving patient adherence. The matrix tablets were fabricated by a direct compression method, the optimized formulation for which was obtained by screening the factors that affected the drug release. Moreover, studies of the pharmacokinetics and hypoglycemic activity as measured by glucose assay kits were performed in dogs. Sustained drug releases profiles over 10h and a reduced influence of medium pHs on release were achieved with the optimized formulation; moreover, the in vivo performance of extended release formulation was also examined, and better absorption, a one-fold decrease in Cmax, a two-fold increase of Tmax and a prolonged hypoglycemic effect compared to the marketed product were observed. In conclusion, sustained RG release and prolonged action were observed with present matrix tablets, which therefore provide a promising formulation for T2D patients who require long-term treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Intermedin A, a New Labdane Diterpene Isolated from Alpinia intermedia, Prolonged the Survival Time of P-388D1 Tumor-Bearing CDF1 Mice.

PubMed

Chen, Lih-Geeng; Su, Pei-Jung; Tsai, Po-Wei; Yang, Ling-Ling; Wang, Ching-Chiung

2017-01-01

Eight ethanolic extracts of indigenous Taiwanese plants of the genus Alpinia were tested for tumor cytotoxicity against AGS, Hep G2, HeLa, KB, and HL-60 cells. Among the 50 % and 95 % EtOH extracts of eight Alpinia species, the cytotoxic effects of Alpinia intermedia leaves were the strongest. When the leaf extract of A. intermedia was partitioned using n -hexane and aqueous solvents, the n -hexane layer showed a greater cytotoxic effect and could prolong the survival time of P-388D 1 tumor-bearing CDF1 mice. Two new labdane diterpene derivatives, intermedin A ( 1 ) and intermedin B ( 2 ), and coronarin E ( 3 ) were isolated from the n -hexane layer of A. intermedia . Intermedin A induced apoptosis in HL-60 cells at 30 µg/mL and significantly prolonged the survival time of P-388D 1 tumor-bearing CDF 1 mice by 48.7 % at 20 mg/kg of body weight. We suggest that intermedin A is a major compound of A. intermedia and has a cytotoxic effect on HL-60 and P-388D 1 cells. Georg Thieme Verlag KG Stuttgart · New York.

Impact of Hypokalemia on Electromechanical Window, Excitation Wavelength and Repolarization Gradients in Guinea-Pig and Rabbit Hearts

PubMed Central

Osadchii, Oleg E.

2014-01-01

Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K+) was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients. PMID:25141124

Small Steps: Preliminary effectiveness and feasibility of an incremental goal-setting intervention to reduce sitting time in older adults.

PubMed

Lewis, L K; Rowlands, A V; Gardiner, P A; Standage, M; English, C; Olds, T

2016-03-01

This study aimed to evaluate the preliminary effectiveness and feasibility of a theory-informed program to reduce sitting time in older adults. Pre-experimental (pre-post) study. Thirty non-working adult (≥ 60 years) participants attended a one hour face-to-face intervention session and were guided through: a review of their sitting time; normative feedback on sitting time; and setting goals to reduce total sitting time and bouts of prolonged sitting. Participants chose six goals and integrated one per week incrementally for six weeks. Participants received weekly phone calls. Sitting time and bouts of prolonged sitting (≥ 30 min) were measured objectively for seven days (activPAL3c inclinometer) pre- and post-intervention. During these periods, a 24-h time recall instrument was administered by computer-assisted telephone interview. Participants completed a post-intervention project evaluation questionnaire. Paired t tests with sequential Bonferroni corrections and Cohen's d effect sizes were calculated for all outcomes. Twenty-seven participants completed the assessments (71.7 ± 6.5 years). Post-intervention, objectively-measured total sitting time was significantly reduced by 51.5 min per day (p=0.006; d=-0.58) and number of bouts of prolonged sitting by 0.8 per day (p=0.002; d=-0.70). Objectively-measured standing increased by 39 min per day (p=0.006; d=0.58). Participants self-reported spending 96 min less per day sitting (p<0.001; d=-0.77) and 32 min less per day watching television (p=0.005; d=-0.59). Participants were highly satisfied with the program. The 'Small Steps' program is a feasible and promising avenue for behavioral modification to reduce sitting time in older adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

PubMed

Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

2016-01-01

To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients

PubMed Central

Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

2017-01-01

Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis. PMID:27793017

Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients.

PubMed

Huang, Lihong; Wei, Yongyue; Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

2017-04-25

Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis.

Targeted benefits of prolonged-infusion piperacillin-tazobactam in an in vitro infection model of Pseudomonas aeruginosa.

PubMed

Zelenitsky, S; Nash, J; Weber, Z; Iacovides, H; Ariano, R

2016-10-01

Given the inconsistent clinical findings, our goal was to characterize the pharmacodynamics (PDs) of prolonged-infusion piperacillin-tazobactam (TZP) in an in vitro pharmacodynamic model of Pseudomonas aeruginosa. Specifically, the study was designed to investigate the influence of MIC on the activity of prolonged-infusion TZP using pharmacokinetics (PKs) consistent with a non-critically ill patient population. There was no benefit with prolonged- compared with standard-infusion TZP against isolates with susceptible MICs of 8 or 16 mg/L. However, prolonged-infusion TZP produced more than two times the final bacterial kill against less susceptible isolates with an intermediate MIC of 32 mg/L. The PDs of TZP were well described by a sigmoid Emax model (r(2) = 0.84) where %ƒT>MIC thresholds of 27 and 75% were associated with bacteriostatic and bactericidal effects, respectively. However, the well-established PD relationship with %ƒT>MIC was not observed with prolonged-infusion TZP. In conclusion, this study characterizes the targeted benefits of prolong-infusion TZP based on pathogen MIC, and supports the assertion that the benefits are selective and most likely observed in patients with less susceptible pathogens or altered PKs.

Successful treatment with levothyroxine for idiopathic hypersomnia patients with subclinical hypothyroidism.

PubMed

Shinno, Hideto; Inami, Yasushi; Inagaki, Takuji; Kawamukai, Tetsuya; Utani, Etsuko; Nakamura, Yu; Horiguchi, Jun

2009-01-01

Our objective was to discuss the effect of levothyroxine on excessive daytime sleepiness (EDS) and a prolonged nocturnal sleep at patients with idiopathic hypersomnia who presented with subclinical hypothyroidism. We present two patients with hypersomnia who complained of EDS and a prolonged nocturnal sleep time. Sleep architecture and subjective daytime sleepiness were estimated by polysomnography (PSG) and Epworth Sleepiness Scale (ESS), respectively. Diagnoses were made using the International Classification of Sleep Disorders, 2nd Edition criteria for idiopathic hypersomnia with long sleep time. PSG demonstrated a short sleep latency, a prolonged total sleep time and normal proportions of all non-rapid eye movement (REM) and REM sleep stages. Nocturnal PSG excluded other causes of EDS. No medical, neurological and mental disorders were present. Their laboratory data indicated mildly elevated thyrotropin, despite free thyroxine (T4) and triiodothyronine (T3) estimates within their reference ranges, which is a characteristic of latent hypothyroidism. Levothyroxine (25 microg/day) was administrated orally. After treatment with levothyroxine for 8 weeks, the mean daily sleep times decreased. EDS was also improved, and a significant decrease in the ESS score was observed. Levothyroxine was effective for their hypersomnia and well tolerated. It should be noted that hypersomnia may be associated with subclinical hypothyroidism, although few abnormalities in physical and neurological examinations are present.

Seed after-ripening and dormancy determine adult life history independently of germination timing.

PubMed

de Casas, Rafael Rubio; Kovach, Katherine; Dittmar, Emily; Barua, Deepak; Barco, Brenden; Donohue, Kathleen

2012-05-01

• Seed dormancy can affect life history through its effects on germination time. Here, we investigate its influence on life history beyond the timing of germination. • We used the response of Arabidopsis thaliana to chilling at the germination and flowering stages to test the following: how seed dormancy affects germination responses to the environment; whether variation in dormancy affects adult phenology independently of germination time; and whether environmental cues experienced by dormant seeds have an effect on adult life history. • Dormancy conditioned the germination response to low temperatures, such that prolonged periods of chilling induced dormancy in nondormant seeds, but stimulated germination in dormant seeds. The alleviation of dormancy through after-ripening was associated with earlier flowering, independent of germination date. Experimental dormancy manipulations showed that prolonged chilling at the seed stage always induced earlier flowering, regardless of seed dormancy. Surprisingly, this effect of seed chilling on flowering time was observed even when low temperatures did not induce germination. • In summary, seed dormancy influences flowering time and hence life history independent of its effects on germination timing. We conclude that the seed stage has a pronounced effect on life history, the influence of which goes well beyond the timing of germination. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Assistive technology and self-rated health in comparison with age peers: a longitudinal study in 55-64-year-olds.

PubMed

Boons, Christel C L M; van de Kamp, Karline; Deeg, Dorly J H

2014-08-26

Abstract Purpose: To determine changes in self-rated health in comparison with age peers (SRH-AP) among 55-64-year-olds, as affected by (1) initiating, (2) ceasing, and (3) prolonging the use of assistive technology (AT). Methods: Data included two national cohorts of 55-64-year-olds from the Longitudinal Aging Study Amsterdam (total N = 1968), with baseline cycles in 1992-93 and 2002-03 and 3-year follow-ups. The effect of AT use on SRH-AP was studied in analyses of variance for repeated measurements, adjusting for age and self-reported disability. Results: Respondents using AT reported poorer SRH-AP than respondents not using AT. Over time disability increased for respondents prolonging and initiating AT use and decreased for respondents ceasing AT use. No major changes were seen in SRH-AP over time, except for a small improvement for respondents prolonging AT use. Conclusions: AT use had a negative influence on SRH-AP, but this influence subsided over time for prolonged AT use. Despite longitudinal changes in disability, there was a marked stability of SRH-AP over time which may be attributed to AT use. Implications for Rehabilitation Both the proportion of 55-64-year-olds using AT and the proportion reporting disability was significantly higher in the recent cohort as compared to the early cohort. 55-64-Year-olds not using AT rated their health compared with age peers (SRH-AP) better than those using AT. 55-64-Year-olds who prolonged the use of AT reported the poorest ratings of SRH-AP, but also showed the clearest improvement in SRH-AP, suggesting that the initial negative influence of AT use on SRH-AP may subside over time.

Computer mouse use predicts acute pain but not prolonged or chronic pain in the neck and shoulder.

PubMed

Andersen, J H; Harhoff, M; Grimstrup, S; Vilstrup, I; Lassen, C F; Brandt, L P A; Kryger, A I; Overgaard, E; Hansen, K D; Mikkelsen, S

2008-02-01

Computer use may have an adverse effect on musculoskeletal outcomes. This study assessed the risk of neck and shoulder pain associated with objectively recorded professional computer use. A computer programme was used to collect data on mouse and keyboard usage and weekly reports of neck and shoulder pain among 2146 technical assistants. Questionnaires were also completed at baseline and at 12 months. The three outcome measures were: (1) acute pain (measured as weekly pain); (2) prolonged pain (no or minor pain in the neck and shoulder region over four consecutive weeks followed by three consecutive weeks with a high pain score); and (3) chronic pain (reported pain or discomfort lasting more than 30 days and "quite a lot of trouble" during the past 12 months). Risk for acute neck pain and shoulder pain increased linearly by 4% and 10%, respectively, for each quartile increase in weekly mouse usage time. Mouse and keyboard usage time did not predict the onset of prolonged or chronic pain in the neck or shoulder. Women had higher risks for neck and shoulder pain. Number of keystrokes and mouse clicks, length of the average activity period, and micro-pauses did not influence reports of acute or prolonged pain. A few psychosocial factors predicted the risk of prolonged pain. Most computer workers have no or minor neck and shoulder pain, few experience prolonged pain, and even fewer, chronic neck and shoulder pain. Moreover, there seems to be no relationship between computer use and prolonged and chronic neck and shoulder pain.

Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation.

PubMed

Lin, Hsin-Hung; Charles, Albert Linton; Hsieh, Chang-Wei; Lee, Ya-Chi; Ciou, Jhih-Ying

2015-01-01

The relationship between the antioxidant activities and inhibitory effect of 14 Chinese medicinal herbs against oxidized low-density lipoprotein (LDL) formation was evaluated. Prolongation of the lag phase of LDL oxidation depended on the concentration of the herbs. The concentration of each herb that was able to prolong the lag time by about two-fold was calculated and expressed as doubling-time concentration. The lower the doubling-time concentration, the stronger the inhibitory effect exhibited toward LDL oxidation. Among them, Chrysanthemi Flos (Chrysanthemum morifolium ramat; gān jú huā), Crataegi Fructus (Crataegus pinnatifida Bge. var. major N.E.Br.; shān zhā), and Roselle (Hibiscus sabdariffa Linn.; luò shén) showed significant inhibitory effects. Correlation coefficients between doubling-time concentration and radical-scavenging activities were high; the total phenolic content was also high. In conclusion, phenolic compounds contributed not only to antioxidant activities, but also to the inhibitory effect against LDL oxidation. Chrysanthemi Flos, Crataegi Fructus, and H. sabdariffa, with lower doubling-time concentrations, could be potent phytochemical agents to reduce LDL oxidation and prevent the progression of atherosclerosis.

Effect of prolonged isothermal heat treatment on the mechanical behavior of advanced NANOBAIN steel

NASA Astrophysics Data System (ADS)

Avishan, Behzad

2017-09-01

The microstructural evolution and consequent changes in strength and ductility of advanced NANOBAIN steel during prolonged isothermal heat-treatment stages were investigated. The microstructure and mechanical properties of nanostructured bainite were not expected to be influenced by extending the heat-treatment time beyond the optimum value because of the autotempering phenomenon and high tempering resistance. However, experimental results indicated that the microstructure was thermodynamically unstable and that prolonged austempering resulted in carbon depletion from high-carbon retained austenite and carbide precipitations. Therefore, austenite became thermally less stable and partially transformed into martensite during cooling to room temperature. Prolonged austempering did not lead to the typical tempering sequence of bainite, and the sizes of the microstructural constituents were independent of the extended heat-treatment times. This independence, in turn, resulted in almost constant ultimate tensile strength values. However, microstructural variations enhanced the yield strength and the hardness of the material at extended isothermal heat-treatment stages. Finally, although microstructural changes decreased the total elongation and impact toughness, considerable combinations of mechanical properties could still be achieved.

Accelerometer-derived sedentary and physical activity time in overweight/obese adults with type 2 diabetes: cross-sectional associations with cardiometabolic biomarkers.

PubMed

Healy, Genevieve N; Winkler, Elisabeth A H; Brakenridge, Charlotte L; Reeves, Marina M; Eakin, Elizabeth G

2015-01-01

To examine the associations of sedentary time and physical activity with biomarkers of cardiometabolic health, including the potential collective impact of shifting mean time use from less- to more-active behaviours (cross-sectionally, using isotemporal substitution), in adults with type 2 diabetes. Participants with overweight/obese body mass index (BMI; ≥25 kg/m2) (n = 279; 158 men, mean [SD] age = 58.2 [8.6] years) wore Actigraph GT1M accelerometers (waking hours; seven days) to assess moderate- to vigorous-intensity physical activity (MVPA), light-intensity activity, and sedentary time (segregated into non-prolonged [accumulated in bouts <30min] and prolonged [accumulated in bouts ≥30 min]). Cross-sectional associations with waist circumference, BMI, fasting blood (HbA1c, glucose, triacylglycerols, high-density lipoprotein cholesterol), and blood pressure of these activity variables (30 min/day increments) were examined adjusted for confounders and wear then, if significant, examined using isotemporal substitution modelling. Waist circumference and BMI were significantly (p<0.05) associated with more prolonged sedentary time and less light-intensity activity. Light intensity activity was also significantly associated with lower fasting plasma glucose (relative rate: 0.98, 95% CI: 0.97, 1.00; p<0.05). No biomarker was significantly associated with non-prolonged sedentary time or MVPA. Lower mean prolonged sedentary time (-30 min/day) with higher mean light intensity time (+30 min/day) was significantly associated with lower waist circumference (β = -0.77, 95% CI: -1.33, -0.22 cm). Lower mean prolonged sedentary time (-30 min/day) with either 30 min/day higher mean non-prolonged sedentary time (β = -0.35, 95%CI: -0.70, -0.01 kg/m2) or light-intensity time (β = -0.36, -0.61, -0.11 kg/m2) was associated with significantly lower average BMI. Significantly improved mean levels of waist circumference and BMI were observed when shifting time from prolonged sedentary to non-prolonged sedentary or light-intensity activity (cross-sectionally). Lifestyle interventions in overweight/obese adults with type 2 diabetes might consider targeting shifts in these non-MVPA activities to more rigorously evaluate their potential cardiometabolic benefit in this population.

Effects of prolonged light exposure times on water sorption, solubility and cross-linking density of simplified etch-and-rinse adhesives.

PubMed

Wambier, Letícia; Malaquias, Tamirez; Wambier, Denise Stadler; Patzlaff, Rafael T; Bauer, José; Loguercio, Alessandro D; Reis, Alessandra

2014-06-01

This study evaluated the effects of light exposure times on water sorption, solubility, and polymer cross-linking density of simplified etch-and-rinse adhesives. Four commercial adhesives (XP Bond, Adper Single Bond 2, Tetric N-Bond, and Ambar) were selected, and resin disks 5 mm in diameter and 1.0 mm thick were prepared and light cured for 20, 40, or 80 s using an LED light-curing unit at 1200 mW/cm2. Water sorption and solubility were evaluated over a 28-day period. For polymer cross-linking density, additional specimens were prepared and their Knoop hardness measured before and after immersion in 100% ethanol. The data from each test were evaluated using a two-way ANOVA and Tukey's test (α = 0.05). The XP Bond adhesive showed higher water sorption (similar to Adper Single Bond 2) and solubility (p < 0.05) than did the other materials. Prolonged exposure times did not reduce the water sorption but did reduce the solubility of all tested materials (p < 0.05). For Ambar, the increase in the exposure time resulted in a significantly lower percent reduction in hardness. Water sorption, solubility, and cross-linking density of the materials selected in this study seem to be mainly influenced by the adhesive composition. Prolonged light exposure times reduced the solubility of the materials.

Long-term evaluation of orbital dynamics in the Sun-planet system considering axial-tilt

NASA Astrophysics Data System (ADS)

Bakhtiari, Majid; Daneshjou, Kamran

2018-05-01

In this paper, the axial-tilt (obliquity) effect of planets on the motion of planets’ orbiter in prolonged space missions has been investigated in the presence of the Sun gravity. The proposed model is based on non-simplified perturbed dynamic equations of planetary orbiter motion. From a new point of view, in this work, the dynamic equations regarding a disturbing body in elliptic inclined three-dimensional orbit are derived. The accuracy of this non-simplified method is validated with dual-averaged method employed on a generalized Earth-Moon system. It is shown that the neglected short-time oscillations in dual-averaged technique can accumulate and propel to remarkable errors in the prolonged evolution. After validation, the effects of the planet’s axial-tilt on eccentricity, inclination and right ascension of the ascending node of the orbiter are investigated. Moreover, a generalized model is provided to study the effects of third-body inclination and eccentricity on orbit characteristics. It is shown that the planet’s axial-tilt is the key to facilitating some significant changes in orbital elements in long-term mission and short-time oscillations must be considered in accurate prolonged evaluation.

Sedentary bout durations and metabolic syndrome among working adults: a prospective cohort study.

PubMed

Honda, Takanori; Chen, Sanmei; Yonemoto, Koji; Kishimoto, Hiro; Chen, Tao; Narazaki, Kenji; Haeuchi, Yuka; Kumagai, Shuzo

2016-08-26

This study aimed to examine the associations between time spent in prolonged and non-prolonged sedentary bouts and the development of metabolic syndrome. We used data from a prospective study of Japanese workers. Baseline examination was conducted between 2010 and 2011. A total of 430 office workers (58 women) aged 40-64 years without metabolic syndrome were followed up by annual health checkups until 2014. Metabolic syndrome was defined as having ≥ 3 out of 5 diagnostic criteria from the Joint Interim Statement 2009 definition. Sedentary time was assessed using a tri-axial accelerometer. Time spent in total, prolonged (accumulated ≥ 30 min) and non-prolonged sedentary bouts (accumulated < 30 min) was calculated. Cox proportional hazards models were used to estimate the risk of developing metabolic syndrome. During a median follow-up of 3 years, 83 participants developed metabolic syndrome. After adjustment for age, sex, education, smoking, and family income, positive associations were observed between time spent in prolonged sedentary bouts and the development of metabolic syndrome. After additional adjustment for moderate-to-vigorous physical activity, those in the three highest quartiles of time spent in prolonged sedentary bouts showed higher risk of metabolic syndrome compared to the lowest quartile group, with adjusted hazard ratios (95 % confidence intervals) of 2.72 (1.30 - 5.73), 2.42 (1.11 - 5.50), and 2.85 (1.31 - 6.18), respectively. No associations were seen for time spent in total and non-prolonged sedentary bouts. Sedentary behavior accumulated in a prolonged manner was associated with an increased risk of metabolic syndrome. In devising public health recommendations for the prevention of metabolic disease, the avoidance of prolonged uninterrupted periods of sedentary behavior should be considered.

The effects of 7.5% NaCl/6% dextran 70 on coagulation and platelet aggregation in humans

NASA Technical Reports Server (NTRS)

Hess, J. R.; Dubick, M. A.; Summary, J. J.; Bangal, N. R.; Wade, C. E.

1992-01-01

The combination solution of 7.5% NaCl/6% dextran 70 (HSD) administered IV gives hemodynamic improvement in the treatment of hemorrhagic hypotension. Since earlier dextran solutions were reported to interfere with blood coagulation, the effects of HSD on the prothrombin time (PT), the activated partial thromboplastin time (APTT), platelet aggregation, and platelet concentration were studied. The HSD mixed with human plasma (1:5 and 1:10) slightly prolonged PT, but had no effect on the APTT, compared with saline controls. The HSD also decreased human platelet aggregation at the 1:5 dilution. In separate mixing studies, the hypertonic saline component of HSD was associated with the prolongation of PT and decreased platelet aggregation. The data from these studies indicate that at its proposed therapeutic dose, HSD is expected to have minimal effect on blood coagulation.

The effectiveness of low-dose desmopressin in improving hypothermia-induced impairment of primary haemostasis under influence of aspirin - a randomized controlled trial.

PubMed

Tsui, Pui Yee; Cheung, Chi Wai; Lee, Yvonne; Leung, Susan Wai Sum; Ng, Kwok Fu Jacobus

2015-05-28

Mild hypothermia (34-35 °C) increases perioperative blood loss. Our previous studies showed that desmopressin could have in vitro beneficial effects on hypothermia-induced primary haemostasis impairment. In this study, we investigate the in vitro effects of desmopressin on hypothermia-induced primary haemostasis impairment under the influence of aspirin in healthy volunteers. Sixty healthy volunteers were randomly allocated to taking aspirin 100 mg or placebo for three days. On the sixth day blood samples were taken before and after the injection of desmopressin (1.5 microgram or 5 microgram) or normal saline subcutaneously. Measurements including Platelet Function Analyzer (PFA-100®) closure times, plasma von Willebrand Factor antigen, haemoglobin and platelet levels were made at 32 °C and 37 °C respectively. Collagen/epinephrine closure time (EPICT) was significantly prolonged by 21.13 % (95 %CI 2.34-39.74 %, p = 0.021) in aspirin group at 37 °C. While hypothermia alone prolonged both collagen/adenosine diphosphate (ADPCT) and EPICT by 17.63 % (95 %CI 13.5-20.85 %, p < 0.001) and 8.0 % (95 %CI 6.38-10.04 %, p = 0.024) respectively, addition of aspirin only further prolonged EPICT by 19.9 % (95 %CI 3.32-36.49 %, p = 0.013). In aspirin group, desmopressin 1.5 microgram and 5 microgram significantly reduced ADPCT to below baseline levels at 37 °C (p = 0.025 and <0.001 respectively), whereas reduction in EPICT was seen with desmopressin 5 microgram (p =0.008). The effect was less pronounced at 32 °C, with a significant reduction in EPICT obtained with a dosage of 5 microgram only (p = 0.011). It was shown that aspirin could further potentiate the hypothermia-induced closure time prolongations. Low dose desmopressin (1.5 microgram) reduced PFA-100® closure times towards baseline. A higher dosage (5 microgram) further reduced the closure times below baseline. Therefore low dose desmopressin (1.5 microgram) might have the potential to correct hypothermia-induced primary haemostasis impairment under the influence of aspirin during the perioperative period. ClinicalTrials.gov: NCT01382134.

Prolonged forearm ischemia attenuates endothelium-dependent vasodilatation and plasma nitric oxide metabolites in overweight middle-aged men.

PubMed

Aboo Bakkar, Zainie; Fulford, Jonathan; Gates, Phillip E; Jackman, Sarah R; Jones, Andrew M; Bond, Bert; Bowtell, Joanna L

2018-05-21

Repeated cycles of endothelial ischemia-reperfusion injury and the resulting respiratory burst contribute to the irreversible pathophysiology of vascular diseases, and yet, the effects of ischemia reperfusion on vascular function, oxidative stress, and nitric oxide (NO) bioavailability have not been assessed simultaneously. Therefore, this study sought to examine the effects of prolonged forearm occlusion and subsequent reperfusion on NO-dependent brachial artery endothelial function. Flow-mediated dilatation was measured at baseline and 15, 30, and 45 min after 20-min forearm occlusion in 14 healthy, but physically inactive middle-aged men (53.7 ± 1.2 years, BMI: 28.1 ± 0.1 kg m -2 ). Venous blood samples collected from the occluded arm were analyzed for NO metabolites and markers of oxidative stress. FMD was significantly depressed after the prolonged occlusion compared to baseline, with a significant reduction 15-min post-occlusion (6.6 ± 0.7 to 2.9 ± 0.4%, p < 0.001); FMD remained depressed after 30 min (4.1 ± 0.6%, p = 0.001), but was not significantly different to baseline after 45-min recovery (5.4 ± 0.7%, p = 0.079). Plasma nitrate (main time effect: p = 0.015) and nitrite (main time effect: p = 0.034) concentrations were significantly reduced after prolonged occlusion. Plasma catalase activity was significantly elevated at 4- (p = 0.016) and 45-min (p = 0.001) post-occlusion, but plasma peroxiredoxin 2 and protein carbonyl content did not change. Prolonged forearm occlusion resulted in acute impairment of endothelium-dependent vasodilatation of the brachial artery for at least 30 min after reperfusion. We demonstrate that this vascular dysfunction is associated with oxidative stress and reduced NO bioavailability following reperfusion.

Paternal work stress and prolonged time to pregnancy.

PubMed

Lee, Mi-Sun; Paek, Domyung; Eum, Ki-Do; Siegrist, Johannes; Li, Jian; Lee, Hye-Eun; Cho, Sung-Il

2009-01-01

The aim of this study was to explore an association between psychosocial stress at work in married men and their spouses' prolonged time to pregnancy (TTP). All married male workers of a large Korean petrochemical enterprise and their wives fulfilling the selection criteria were included. Main selection criteria were lack of use of contraceptives and experienced pregnancy in recent past. Data were available from 322 couples. Psychosocial stress at work was measured by the effort-reward imbalance questionnaire. Prolonged TTP was measured by the "TTP questionnaire". After adjustment for confounding effects of demographic and life-style characteristics and benzene exposure, delayed TTP, defined by frequency of first-cycle pregnancy, was associated with one standard deviation (SD) increase of the effort-reward ratio in the chronically stressed group of married men (OR = 0.47; 95% CI = 0.22-0.99) in logistic regression analysis. A similar, but somewhat weaker effect, was found for the overall group (OR = 0.67; 95% CI = 0.47-0.94). Paternal stress at work, as measured by effort-reward imbalance, seemed to be associated with a decreased number of conceptions in the first menstrual cycle.

Effect of local cooling on excitation-contraction coupling in myasthenic muscle: Another mechanism of ice-pack test in myasthenia gravis.

PubMed

Yamamoto, Daisuke; Imai, Tomihiro; Tsuda, Emiko; Hozuki, Takayoshi; Yamauchi, Rika; Hisahara, Shin; Kawamata, Jun; Shimohama, Shun

2017-11-01

The ice-pack test is a convenient diagnostic testing procedure for myasthenia gravis (MG). We investigated the underlying mechanism of the ice-pack test performed on bilateral masseters. We performed trigeminal repetitive nerve stimulation (RNS), excitation-contraction (E-C) coupling assessment (Imai's method) and bite force measurement before and after cooling of the masseters in MG patients and normal controls. After placing the ice-pack on the masseters for 3min, serial recordings of the three tests were performed at various time intervals during 10min after cooling. The bite force increased significantly after cooling in ice-pack-positive MG patients. The acceleration and acceleration ratio (acceleration at a given time to baseline acceleration) of jaw movement increased significantly after cooling of the masseters in ice-pack-positive MG patients compared to ice-pack-negative patients and normal controls. The prolonged effect of cooling continued until the end of recording even though decremental response to RNS had returned to baseline value. Cooling of myasthenic muscle may induce two effects. One is relatively short effect on electrical synaptic transmission at the endplate, and another is prolonged effect on E-C coupling in the muscle. The ice-pack test induces a prolonged effect of ameliorating impaired E-C coupling in MG. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Mixing Time Effects on the Dispersion Performance of Adhesive Mixtures for Inhalation

PubMed Central

Grasmeijer, Floris; Hagedoorn, Paul; Frijlink, Henderik W.; de Boer, H. Anne

2013-01-01

This paper deals with the effects of mixing time on the homogeneity and dispersion performance of adhesive mixtures for inhalation. Interactions between these effects and the carrier size fraction, the type of drug and the inhalation flow rate were studied. Furthermore, it was examined whether or not changes in the dispersion performance as a result of prolonged mixing can be explained with a balance of three processes that occur during mixing, knowing drug redistribution over the lactose carrier; (de-) agglomeration of the drug (and fine lactose) particles; and compression of the drug particles onto the carrier surface. For this purpose, mixtures containing salmeterol xinafoate or fluticasone propionate were mixed for different periods of time with a fine or coarse crystalline lactose carrier in a Turbula mixer. Drug detachment experiments were performed using a classifier based inhaler at different flow rates. Scanning electron microscopy and laser diffraction techniques were used to measure drug distribution and agglomeration, whereas changes in the apparent solubility were measured as a means to monitor the degree of mechanical stress imparted on the drug particles. No clear trend between mixing time and content uniformity was observed. Quantitative and qualitative interactions between the effect of mixing time on drug detachment and the type of drug, the carrier size fraction and the flow rate were measured, which could be explained with the three processes mentioned. Generally, prolonged mixing caused drug detachment to decrease, with the strongest decline occurring in the first 120 minutes of mixing. For the most cohesive drug (salmeterol) and the coarse carrier, agglomerate formation seemed to dominate the overall effect of mixing time at a low inhalation flow rate, causing drug detachment to increase with prolonged mixing. The optimal mixing time will thus depend on the formulation purpose and the choice for other, interacting variables. PMID:23844256

Prolonged restricted sitting effects in UH-60 helicopters.

PubMed

Games, Kenneth E; Lakin, Joni M; Quindry, John C; Weimar, Wendi H; Sefton, JoEllen M

2015-01-01

Advances in flight technologies and the demand for long-range flight have increased mission lengths for U.S. Army Black Hawk UH-60 crewmembers. Prolonged mission times have increased reports of pilot discomfort and symptoms of paresthesia thought to be due to UH-60 seat design and areas of locally high pressure. Discomfort created by the seat-system decreases situational awareness, putting aviators and support crew at risk of injury. Therefore, the purpose of this study was to examine the effects of prolonged restricted sitting in a UH-60 on discomfort, sensory function, and vascular measures in the lower extremities. There were 15 healthy men (age = 23.4 ± 3.1 yr) meeting physical flight status requirements who sat in an unpadded, UH-60 pilot's seat for 4 h while completing a common cognitive task. During the session, subjective discomfort, sensory function, and vascular function were measured. Across 4 h of restricted sitting, subjective discomfort increased using the Category Partitioning Scale (30.27 point increase) and McGill Pain Questionnaire (8.53 point increase); lower extremity sensory function was diminished along the S1 dermatome; and skin temperature decreased on both the lateral (2.85°C decrease) and anterior (2.78°C decrease) aspects of the ankle. The results suggest that prolonged sitting in a UH-60 seat increases discomfort, potentially through a peripheral nervous or vascular system mechanism. Further research is needed to understand the etiology and onset of pain and paresthesia during prolonged sitting in UH-60 pilot seats. Games KE, Lakin JM, Quindry JC, Weimar WH, Sefton JM. Prolonged restricted sitting effects in UH-60 helicopters.

Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats.

PubMed

Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki

2010-08-01

Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation. Thrombus formation was initiated by FeCl(3)-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle. TAK-442 (3mg/kg, po), aspirin (100mg/kg, po) or clopidogrel (3mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment. These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings. (c) 2010 Elsevier Ltd. All rights reserved.

Reducing office workers’ sitting time: rationale and study design for the Stand Up Victoria cluster randomized trial

PubMed Central

2013-01-01

Background Excessive time spent in sedentary behaviours (sitting or lying with low energy expenditure) is associated with an increased risk for type 2 diabetes, cardiovascular disease and some cancers. Desk-based office workers typically accumulate high amounts of daily sitting time, often in prolonged unbroken bouts. The Stand Up Victoria study aims to determine whether a 3-month multi-component intervention in the office setting reduces workplace sitting, particularly prolonged, unbroken sitting time, and results in improvements in cardio-metabolic biomarkers and work-related outcomes, compared to usual practice. Methods/Design A two-arm cluster-randomized controlled trial (RCT), with worksites as the unit of randomization, will be conducted in 16 worksites located in Victoria, Australia. Work units from one organisation (Department of Human Services, Australian Government) will be allocated to either the multi-component intervention (organisational, environmental [height-adjustable workstations], and individual behavioural strategies) or to a usual practice control group. The recruitment target is 160 participants (office-based workers aged 18–65 years and working at least 0.6 full time equivalent) per arm. At each assessment (0- [baseline], 3- [post intervention], and 12-months [follow-up]), objective measurement via the activPAL3 activity monitor will be used to assess workplace: sitting time (primary outcome); prolonged sitting time (sitting time accrued in bouts of ≥30 minutes); standing time; sit-to-stand transitions; and, moving time. Additional outcomes assessed will include: non-workplace activity; cardio-metabolic biomarkers and health indicators (including fasting glucose, lipids and insulin; anthropometric measures; blood pressure; and, musculoskeletal symptoms); and, work-related outcomes (presenteeism, absenteeism, productivity, work performance). Incremental cost-effectiveness and identification of both workplace and individual-level mediators and moderators of change will also be evaluated. Discussion Stand Up Victoria will be the first cluster-RCT to evaluate the effectiveness of a multi-component intervention aimed at reducing prolonged workplace sitting in office workers. Strengths include the objective measurement of activity and assessment of the intervention on markers of cardio-metabolic health. Health- and work-related benefits, as well as the cost-effectiveness of the intervention, will help to inform future occupational practice. Trial registration ACTRN1211000742976 PMID:24209423

Sedentary Behavior and Sleep Duration Are Associated with Both Stress Symptoms and Suicidal Thoughts in Korean Adults.

PubMed

An, Keun Ok; Jang, Jae Yong; Kim, Junghoon

2015-12-01

Prolonged sedentary time and sleep deprivation are associated with mental health problems such as depression and stress symptoms. Moreover, mental illness is linked with suicidal thoughts and suicide attempts. However, it is not clear whether sedentary time and sleep duration are associated with stress symptoms and suicidal thoughts independent of physical activity. Thus, our study aimed to identify if sedentary time and sleep duration were associated with both stress symptoms and suicidal thoughts. The participants in present cross-sectional study were 4,674 general Korean adults (1,938 male; 2,736 female), aged ≥ 20 years. Prolonged sedentary time (≥ 420 min/day) was significantly associated with the increased risk of stress symptoms (OR, 1.30; 95% CI, 1.04-1.62) compared with sedentary time of < 240 min/day. The OR for stress symptoms was significant for individuals who had ≤ 5 h/day of sleep time (OR, 1.88; 95% CI, 1.48-2.38) compared with sleep duration of ≥ 7 h/day. Moreover, prolonged sedentary time (OR, 1.55; 95% CI, 1.01-2.42 in ≥ 420 min/day vs. < 240 min/day) and short sleep duration (OR, 1.75; 95% CI, 1.17-2.62 in ≤ 5 h/day vs. ≥ 7 h/day) were significantly associated with an increased risk for suicidal thoughts after adjusting for confounding factors including physical activity. Thus, prolonged sedentary time and sleep deprivation are independently associated with both the risk of stress symptoms and suicidal thoughts. From a public health perspective, reducing sedentary time and improvement of sleep deprivation may serve as an effective strategy for preventing mental illness.

Methoxyflurane anesthesia augments the chronotropic and dromotropic effects of verapamil.

PubMed

Jamali, F; Mayo, P R

1999-01-01

Inhalation anesthetics have been shown to have electrical suppressant effects on excitable membranes such as the cardiac conduction system. Therefore, the anesthetized patient or laboratory animal may respond differently to cardiac drugs when compared with their conscious counterparts. The purpose of this study was to assess the effects of anesthesia with methoxyflurane (MF) on the dromotropic and chronotropic effects of verapamil (VER) in the rat. A lead I ECG was measured using subcutaneous electrodes placed both axilli and over the xyphoid process in male Sprague-Dawley rats. Dromotropic effect was measured using the PR-interval which indicated the electrical spread across the atria to the AV-node and chronotropic effects were determined using RR-interval. A total of six animals were randomized to receive 10 mg/kg s.c. of verapamil in the presence or absence of general anesthesia containing methoxyflurane. In addition, PR-interval and RR-intervals were determined in the presence of only methoxyflurane and at rest without any drug exposure. The time for the ECG to normalize after exposure to methoxyflurane and/or verapamil was also determined. Exposure to verapamil alone resulted in a 5% prolongation in PR-interval and 6% prolongation in RR-interval. Methoxyflurane alone had a larger effect than verapamil demonstrating a 14.5% prolongation in PR-interval and a 12.3% in RR-interval which was statistically significant. The combination of MF + VER resulted in a synergistic prolongation in PR-interval to 28. 7% while the effect on RR-interval was additive with an increase to 17.6%. The time for the ECG to normalize after exposure to VER, MF and VER + MF was 37.5 15.1 min, 69.8 5.3 min, and 148.5 +/- 6.6 min respectively. General anesthesia with MF enhances the dromotropic and chronotropic effect of VER. This should be considered when MF-anesthesia is used in experimental procedure.

Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig.

PubMed

Sun, Hong-Li; Chu, Wen-Feng; Dong, De-Li; Liu, Yan; Bai, Yun-Long; Wang, Xiao-Hui; Zhou, Jin; Yang, Bao-Feng

2006-04-01

Arsenic trioxide (As(2)O(3)) has been found to be effective for relapsed or refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim of the present study was to elucidate the ionic mechanisms of As(2)O(3)-induced abnormalities of cardiac electrophysiology and the therapeutic action of choline on As(2)O(3)-caused QT prolongation in guinea pig. Intravenous administration of As(2)O(3) prolonged the QT interval in a dose- and time-dependent manner in guinea pig hearts, and the QT prolongation could be modulated by choline. By using whole-cell patch clamp technique and confocal laser scanning microscopy, we found that As(2)O(3) significantly lengthened action potential duration measured at 50 and 90% of repolarization, enhanced L-type calcium currents (I(Ca-L)), inhibited delayed rectifier potassium currents (I(K)), and increased intracellular calcium concentration ([Ca(2+)](i)) in guinea pig ventricular myocytes. Choline corrected As(2)O(3)-mediated alterations of action potential duration, I(Ca-L) and [Ca(2+)](i), but had no effect on the I(K) inhibition. As(2)O(3) markedly disturbed the normal equilibrium of transmembrane currents (increasing I(Ca-L) and suppressing I(K)) in guinea pig cardiomyocyte, and induced prolongation of action potential duration, further degenerated into QT prolongation. Choline normalized QT interval abnormality and corrected lengthened action potential duration by inhibiting the elevated I(Ca-L) and [Ca(2+)](i) in ventricular myocytes during As(2)O(3) application.

Effect of Dexamethasone on Characteristics of Supraclavicular Nerve Block with Bupivacaine and Ropivacaine: A Prospective, Double-blind, Randomized Control Trial.

PubMed

Bindal, Deeksha; Narang, Neeraj; Mahindra, Rekha; Gupta, Himanshu; Kubre, Jyotsna; Saxena, Anudeep

2018-01-01

Dexamethasone as an adjuvant to bupivacaine and ropivacaine for supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade. However, comparison of effect of dexamethasone (8 mg) when added to these two local anesthetics has not been well studied. This study was conducted to compare analgesic efficacy of dexamethasone as adjuvant to bupivacaine and ropivacaine in SCBP block. Nerve stimulator-guided SCBP block was given to 120 patients, randomly assigned to one of four groups: ( n = 30 in each group) Group B, BD, R, and RD received 30 ml (0.5%) bupivacaine + 2 ml saline, 30 ml (0.5%) bupivacaine + dexamethasone 8 mg, 30 ml (0.5%) ropivacaine + 2 ml saline, and 30 ml (0.5%) ropivacaine + dexamethasone 8 mg, respectively. Time for request of the first rescue analgesic, 24-h analgesic consumption, and different block characteristics were assessed. Student's t -test, Chi-square test, ANOVA were used for statistical analysis. Dexamethasone significantly prolonged time for request of the first rescue analgesic of both ropivacaine (1211.83 ± 32.86 vs. 283.17 ± 7.71 min){ p R, RD < 0.001} and bupivacaine (1205.17 ± 34.32 vs. 364.67 ± 16.50 min) {p B, BD < 0.001}. 24-h requirement for rescue analgesics was more in Groups B and R when compared to Groups BD and RD. The increase in duration of analgesia was more when Groups R and RD (928.66 min) were compared than Groups B and BD (840.5 min). Similar results were seen with onset times and duration of sensory and motor block. The addition of dexamethasone to bupivacaine and ropivacaine in SCBP block prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block, with the effect being stronger with ropivacaine.

Evaluating the effectiveness of organisational-level strategies with or without an activity tracker to reduce office workers' sitting time: a cluster-randomised trial.

PubMed

Brakenridge, C L; Fjeldsoe, B S; Young, D C; Winkler, E A H; Dunstan, D W; Straker, L M; Healy, G N

2016-11-04

Office workers engage in high levels of sitting time. Effective, context-specific, and scalable strategies are needed to support widespread sitting reduction. This study aimed to evaluate organisational-support strategies alone or in combination with an activity tracker to reduce sitting in office workers. From one organisation, 153 desk-based office workers were cluster-randomised (by team) to organisational support only (e.g., manager support, emails; 'Group ORG', 9 teams, 87 participants), or organisational support plus LUMOback activity tracker ('Group ORG + Tracker', 9 teams, 66 participants). The waist-worn tracker provided real-time feedback and prompts on sitting and posture. ActivPAL3 monitors were used to ascertain primary outcomes (sitting time during work- and overall hours) and other activity outcomes: prolonged sitting time (≥30 min bouts), time between sitting bouts, standing time, stepping time, and number of steps. Health and work outcomes were assessed by questionnaire. Changes within each group (three- and 12 months) and differences between groups were analysed by linear mixed models. Missing data were multiply imputed. At baseline, participants (46 % women, 23-58 years) spent (mean ± SD) 74.3 ± 9.7 % of their workday sitting, 17.5 ± 8.3 % standing and 8.1 ± 2.7 % stepping. Significant (p < 0.05) reductions in sitting time (both work and overall) were observed within both groups, but only at 12 months. For secondary activity outcomes, Group ORG significantly improved in work prolonged sitting, time between sitting bouts and standing time, and overall prolonged sitting time (12 months), and in overall standing time (three- and 12 months); while Group ORG + Tracker, significantly improved in work prolonged sitting, standing, stepping and overall standing time (12 months). Adjusted for confounders, the only significant between-group differences were a greater stepping time and step count for Group ORG + Tracker relative to Group ORG (+20.6 min/16 h day, 95 % CI: 3.1, 38.1, p = 0.021; +846.5steps/16 h day, 95 % CI: 67.8, 1625.2, p = 0.033) at 12 months. Observed changes in health and work outcomes were small and not statistically significant. Organisational-support strategies with or without an activity tracker resulted in improvements in sitting, prolonged sitting and standing; adding a tracker enhanced stepping changes. Improvements were most evident at 12 months, suggesting the organisational-support strategies may have taken time to embed within the organisation. Australian New Zealand Clinical Trial Registry: ACTRN12614000252617 . Registered 10 March 2014.

Web-PE: Internet-Delivered Prolonged Exposure Therapy for PTSD

DTIC Science & Technology

2015-10-01

order to meet the growing demand for effective and efficient treatment for posttraumatic stress disorder ( PTSD ) in a timely manner. Web-treatments...posttraumatic stress disorder ( PTSD ) in a timely manner. Effective EBTs for PTSD are available, but barriers to accessing care can deter military...Exposure, combat, psychological treatment, military, psychotherapy, trauma, posttraumatic stress , posttraumatic stress disorder 16. SECURITY

Radionuclide gastric emptying studies in patients with anorexia nervosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Domstad, P.A.; Shih, W.J.; Humphries, L.

1987-05-01

To evaluate gastric emptying in anorexia nervosa patients, 26 patients (17 females, two males, ranging in age from 13 to 40 yr) with upper GI symptoms ingested 150-200 microCi (/sup 99m/Tc)triethelenetetraamine polysterene resin in cereal and were imaged in the supine position. Data were accumulated at 5 min intervals to obtain the gastric emptying time (GET). The results of the studies were divided into three categories: prolonged, 13 patients; rapid, 11; and normal 3. Twelve of 13 patients with prolonged GET were given 10 mg metoclopramide i.v. injections; nine of the 12 patients had a good response and three hadmore » no response. Five of the nine patients underwent metoclopramide therapy and four of the patients showed benefit from the therapy. One patient discontinued metoclopramide therapy because of somnolence. Although all patients had subjective symptoms of gastric dysfunction, our results indicated only 50% had objectively prolonged GET, and another 50% showed normal or even rapid GET. Therefore, this radionuclide study enables quantitatively objective documentation of gastric emptying, separation of those patients with rapid or normal GET from those with prolonged GET, thereby avoiding the possible side effects from metoclopramide medication, and prediction of effectiveness of metoclopramide therapy in patients with prolonged GET.« less

Yerba Maté (Ilex paraguariensis) Metabolic, Satiety, and Mood State Effects at Rest and during Prolonged Exercise.

PubMed

Alkhatib, Ahmad; Atcheson, Roisin

2017-08-15

Yerba Maté (YM), has become a popular herb ingested for enhancing metabolic health and weight-loss outcomes. No studies have tested the combined metabolic, satiety, and psychomotor effects of YM during exercise. We tested whether YM ingestion affects fatty acid oxidation (FAO), profile of mood state score (POMS), and subjective appetite scale (VAS), during prolonged moderate exercise. Twelve healthy active females were randomized to ingest either 2 g of YM or placebo (PLC) in a repeated-measures design. Participants rested for 120 min before performing a 30-min cycling exercise corresponding to individuals' crossover point intensity (COP). FAO, determined using indirect calorimetry, was significantly higher during the 30-min exercise in YM vs. PLC (0.21 ± 0.07 vs. 0.17 ± 0.06 g/min, p < 0.05). VAS scores for hunger, prospective eating, and desire to eat were all reduced ( p < 0.05). Whereas, POMS measures of focus, energy, and concentration were all increased ( p < 0.05). There was no significant time-effect for any of the measured variables, nor was there any interaction effects between YM treatment and time. Combining YM intake with prolonged exercise at targeted "fat-loss"' intensities augments FAO and improves measures of satiety and mood state. Such positive combined metabolic, satiety, and psychomotor effects may provide an important role for designing future fat and weight-loss lifestyle interventions.

Comparative toxicity of diphacinone to northern bobwhite (Colinus virginianus) and American kestrels (Falco sparverius)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Johnston, John J.

2010-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell's Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell's Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species.

Effectiveness of ice-vest cooling in prolonging work tolerance time during heavy exercise in the heat for personnel wearing Canadian forces chemical defense ensembles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bain, B.

Effectiveness of a portable, ice-pack cooling vest (Steelevest) in prolonging work tolerance time in chemical defense clothing in the heat (33 C dry bulb, 33% relative humidity or 25 C WBGT) was evaluated while subjects exercised at a metabolic rate of approx. 700 watts. Subjects were six male volunteers. The protocol consisted of a 20 minute treadmill walk at 1.33 m/s. and 7.5% grade, followed by 15 minutes of a lifting task, 5 minutes rest, then another 20 minutes of lifting task for a total of one hour. The lifting task consisted of lifting of 20 kg box, carrying itmore » 3 meters and setting it down. This was followed by a 6 m walk (3m back to the start point and 3 m back to the box) 15 sec after which the lifting cycle began again. The work was classified as heavy as previously defined. This protocol was repeated until the subjects were unable to continue or they reached a physiological endpoint. Time to voluntary cessation or physiological endpoint was called the work tolerance time. Physiological endpoints were rectal temperature of 39 C, heart rate exceeding 95% of maximum for two consecutive minutes or visible loss of motor control or nausea. The cooling vest had no effect on work tolerance time, rate of rise of rectal temperature or sweat loss. It was concluded that the Steelvest ice-vest is ineffective in prolonging work tolerance time and preventing increases in rectal temperature while wearing chemical protective clothing.« less

Survival of Listeria monocytogenes and Staphylococcus aureus in Synthetic Brines. Studying the Effects of Salt, Temperature and Sugar through the Approach of the Design of Experiments.

PubMed

Bevilacqua, Antonio; Campaniello, Daniela; Speranza, Barbara; Sinigaglia, Milena; Corbo, Maria R

2018-01-01

The fermentation of table olives relies on a complex microbiota of lactic acid bacteria (LAB), yeasts, and enterobacteria. Producers often add sugar to increase the growth rate of LAB, "but this practice could also increase the survival rate of some pathogens. Therefore, the main topic of this paper was to study the effect of sugar, salt and temperature on the survival of Staphylococcus aureus and Listeria monocytogenes in a synthetic brine through the theory of the Design of Experiments (simplex centroid). The addition of sugar could prolong the survival time of L. monocytogenes by 40 days, whereas an increase of the temperature caused a decrease of survival from 18 to 3 days. The survival time of S. aureus was prolonged by 50 days by combining sugar (2-4 g/l) and low temperatures (5-15°C). The use of desirability approach and prediction profiles suggests that the prolongation of the survival time of L. monocytogenes could be related to a shift in the geometrical shape of the death kinetic. This paper offers a structured statistical approach on the variables acting on the survival of two pathogens in brines and represents the first step to set up and design a predictive approach for olive producers.

The differential effects of prolonged exercise upon executive function and cerebral oxygenation.

PubMed

Tempest, Gavin D; Davranche, Karen; Brisswalter, Jeanick; Perrey, Stephane; Radel, Rémi

2017-04-01

The acute-exercise effects upon cognitive functions are varied and dependent upon exercise duration and intensity, and the type of cognitive tasks assessed. The hypofrontality hypothesis assumes that prolonged exercise, at physiologically challenging intensities, is detrimental to executive functions due to cerebral perturbations (indicated by reduced prefrontal activity). The present study aimed to test this hypothesis by measuring oxygenation in prefrontal and motor regions using near-infrared spectroscopy during two executive tasks (flanker task and 2-back task) performed while cycling for 60min at a very low intensity and an intensity above the ventilatory threshold. Findings revealed that, compared to very low intensity, physiologically challenging exercise (i) shortened reaction time in the flanker task, (ii) impaired performance in the 2-back task, and (iii) initially increased oxygenation in prefrontal, but not motor regions, which then became stable in both regions over time. Therefore, during prolonged exercise, not only is the intensity of exercise assessed important, but also the nature of the cognitive processes involved in the task. In contrast to the hypofrontality hypothesis, no inverse pattern of oxygenation between prefrontal and motor regions was observed, and prefrontal oxygenation was maintained over time. The present results go against the hypofrontality hypothesis. Copyright © 2017 Elsevier Inc. All rights reserved.

[Effect of Low Molecular Weight Heparin Calcium Combined Compound Danshen Injection on Perinatal Outcomes of Nephrotic Syndrome Patients with Early Onset Severe Pre-eclampsia].

PubMed

Tong, Chong-xin; Xing, Xiao-fen; Qiao, Shu-hua; Liu, Lin; Shan, Ling

2015-08-01

To observe the effect of low molecular weight heparin calcium (LMWHC) combined Compound Danshen Injection (DI) on nephrotic syndrome patients with early onset severe preeclampsia. Totally 80 nephrotic syndrome patients with early onset severe pre-eclampsia were randomly assigned to four groups voluntarily, i.e., Group A (22 cases, treated by magnesium sulfate), B (19 cases, treated by magnesium sulfate plus LMWHC), C (21 cases, magnesium sulfate plus DI), D (18 cases, magnesium sulfate plus LMWHC and DI). Umbilical arterial S/D ratios, amniotic fluid index (AFI), prolonged gestational age, placenta weight, neonatal weight, and Apgar score were compared among the four groups. Compared with before treatment in the same group, umbilical arterial S/D ratios decreased in the four groups (P <0. 05). AFI decreased in Group A, while it increased in Group B, C, and D (P<0. 05). Compared with Group A at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group B, C, and D (P <0. 01 , P <0. 05). Prolonged gestational age and neonatal weight were increased in Group B, C, and D (P <0. 01, P <0. 05). Placenta weight were increased in Group B and D (P <0. 05). Apgar scores at 1 and 5 min were improved in Group D (P <0. 05). Compared with Group B and C at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group D (P<0. 05). Compared with Group B, prolonged gestational age and placenta weight were decreased in Group C, but prolonged gestational age and placenta weight were increased in Group D (P <0.05). Compared with Group C, prolonged gestational age, placenta weight, and neonatal weight were increased in Group D (P <0. 05). Treatment of nephrotic syndrome patients with early onset severe pre-eclampsia by LMWHC combined DI could prolong gestational ages, obviously improve prenatal outcomes, with better effect obtained than using any of them alone.

The Effects of Phrenic Nerve Degeneration by Axotomy and Crush on the Electrical Activities of Diaphragm Muscles of Rats.

PubMed

Alkiş, Mehmet Eşref; Kavak, Servet; Sayır, Fuat; Him, Aydin

2016-03-01

The aim of this study was to investigate the effect of axotomy and crush-related degeneration on the electrical activities of diaphragm muscle strips of experimental rats. In the present study, twenty-one male Wistar-albino rats were used and divided into three groups. The animals in the first group were not crushed or axotomized and served as controls. Phrenic nerves of the rats in the second and third groups were crushed or axotomized in the diaphragm muscle. Resting membrane potential (RMP) was decreased significantly in both crush and axotomy of diaphragm muscle strips of experimental rats (p < 0.05). Depolarization time (T DEP) and half-repolarization (1/2 RT) time were significantly prolonged in crush and axotomy rats (p < 0.05). Crushing or axotomizing the phrenic nerves may produce electrical activities in the diaphragm muscle of the rat by depolarization time and half-repolarization time prolonged in crush and axotomy rats.

Pharmacological Differentiation of Thrombomodulin Alfa and Activated Protein C on Coagulation and Fibrinolysis In Vitro.

PubMed

Tanaka, Kosuke; Tawara, Shunsuke; Tsuruta, Kazuhisa; Hoppensteadt, Debra; Fareed, Jawed

2018-01-01

Although thrombomodulin alfa (TM alfa), recombinant human soluble thrombomodulin, exerts antithrombogenic effects through activated protein C (APC), clinical trials suggested that TM alfa has a lower bleeding risk than does recombinant human APC. To address the mechanism explaining this difference, effects of TM alfa and APC on thrombogenic, coagulation, and fibrinolytic processes were compared in vitro. TM alfa and APC inhibited generation of thrombogenic markers, thrombin, and prothrombin fragment F1+2 and prolonged coagulation parameters, activated clotting time (ACT), and activated partial thromboplastin time (APTT). Concentrations of TM alfa effective for thrombin and F1+2 generation inhibition were comparable to those of APC. However, effects of TM alfa on ACT and APTT were clearly weaker than those of APC. TM alfa significantly prolonged clot lysis time (CLT) and decreased LY30, a parameter of degree of fibrinolysis in thromboelastography, whereas APC significantly shortened CLT and increased LY30. These results suggested that while the antithrombogenic effects of TM alfa were similar to those of APC, its anticoagulant effects were lower. In addition, effects of TM alfa were antifibrinolytic, while those of APC were profibrinolytic.

Can We Predict Cognitive Performance Decrements Due to Sleep Loss and the Recuperative Effects of Caffeine

DTIC Science & Technology

2015-10-14

such as timely short naps and caffeine, are often used to mitigate the effects of sleep loss on performance. However, the timing, duration, and dosage...loss and the restorative effects of different dosages of caffeine on a specific individual’s performance. When used as a decision-aid tool, this model...provides the means to maximize Warfighter cognitive performance, resulting in peak alertness and prolonged alertness at the desired times

In vitro effects of 3% hypertonic saline and 20% mannitol on canine whole blood coagulation and platelet function.

PubMed

Adamik, Katja-Nicole; Butty, Emmanuelle; Howard, Judith

2015-09-24

Hyperosmolar therapy, using either mannitol or hypertonic saline (HTS), is considered the treatment of choice for intracranial hypertension. However, hyperosmolar agents may impair coagulation and platelet function, limiting their use in patients at risk for hemorrhage. Despite this, studies evaluating the effects of mannitol compared to other hyperosmolar agents in dogs are largely lacking. The aim of this study was to compare the in vitro effects on global hemostasis and platelet function of 20% mannitol and 3% HTS on canine blood. Citrated whole blood from 15 healthy dogs was diluted with 0.9% saline, 20% mannitol and 3% HTS in ratios of 1:16 and 1:8. Rotational thromboelastometry (ROTEM) was used to assess clotting time (CT), clot formation time (CFT) and maximal clot firmness (MCF) following extrinsic activation (Ex-tem) and after platelet inhibition (Fib-tem). A platelet function analyzer (PFA-100) was used to assess closure time (Ct(PFA)). No significant differences were observed between untreated whole blood and samples diluted with saline. Samples diluted with both mannitol and HTS were hypocoagulable compared to untreated whole blood samples. At a dilution of 1:16, no significant differences were found between any measured parameter in samples diluted with saline compared to mannitol or HTS. At a 1:8 dilution, Ct(PFA) was prolonged in samples diluted with mannitol and HTS compared to saline, and Ct(PFA) was prolonged more with mannitol than HTS. Ex-tem CT was increased at a 1:8 dilution with mannitol compared to HTS. Ex-tem CFT was prolonged at a 1:8 dilution with both agents compared to saline, and was prolonged more with mannitol than HTS. Ex-tem MCF was reduced at a 1:8 dilution with both agents compared to saline. Data in this study indicate that both mannitol and HTS affect canine platelet function and whole blood coagulation in vitro in a dose-dependent fashion. The most pronounced effects were observed after high dilutions with mannitol, which impaired platelet aggregation, clot formation time, clot strength, and fibrin formation significantly more than HTS. Further in vivo studies are necessary before recommendations can be made.

Value of Formalin Fixation for the Prolonged Preservation of Rodent Myocardial Microanatomical Organization: Evidence by MR Diffusion Tensor Imaging.

PubMed

Giannakidis, Archontis; Gullberg, Grant T; Pennell, Dudley J; Firmin, David N

2016-07-01

Previous ex vivo diffusion tensor imaging (DTI) studies on formalin-fixed myocardial tissue assumed that, after some initial changes in the first 48 hr since the start of fixation, DTI parameters remain stable over time. Prolonged preservation of cardiac tissue in formalin prior to imaging has been seen many times in the DTI literature as it is considered orderly. Our objective is to define the effects of the prolonged cardiac tissue exposure to formalin on tissue microanatomical organization, as this is assessed by DTI parameters. DTI experiments were conducted on eight excised rodent hearts that were fixed by immersion in formalin. The samples were randomly divided into two equinumerous groups corresponding to shorter (∼2 weeks) and more prolonged (∼6-8 weeks) durations of tissue exposure to formalin prior to imaging. We found that when the duration of cardiac tissue exposure to formalin before imaging increased, water diffusion became less restricted, helix angle (HA) histograms flattened out and exhibited heavier tails (even though the classic HA transmural variation was preserved), and a significant loss of inter-voxel primary diffusion orientation integrity was introduced. The prolonged preservation of cardiac tissue in formalin profoundly affected its microstructural organization, as this was assessed by DTI parameters. The accurate interpretation of diffusivity profiles necessitates awareness of the pitfalls of prolonged cardiac tissue exposure duration to formalin. The acquired knowledge works to the advantage of a proper experimental design of DTI studies of fixed hearts. Anat Rec, 299:878-887, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice: increased small intestinal crypt survival, crypt lengths and prolongation of average time to death.

PubMed

Ohara, M; Lu, H; Shiraki, K; Ishimura, Y; Uesaka, T; Katoh, O; Watanabe, H

2001-12-01

The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60Co-gamma-ray irradiation at a dose rate of 2Gy min(-1). Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min(-1), the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects.

Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1.

PubMed

Xu, Yanli; Xu, Shan; Cai, Yueqin; Liu, Luming

2015-01-01

The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ) on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1) was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08-50 mg/mL) of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine). mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L) in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option.

Down-Regulation of Protein Kinase C-ε by Prolonged Incubation with PMA Inhibits the Proliferation of Vascular Smooth Muscle Cells.

PubMed

Zhou, Huixuan; Wang, Yan; Zhou, Quanhong; Wu, Bin; Wang, Aizhong; Jiang, Wei; Wang, Li

2016-01-01

Phorbol myristate acetate (PMA) exerts a pleiotropic effect on the growth and differentiation of various cells. Protein kinase Cs (PKCs) plays a central role in mediating the effects of PMA on cells. The present study investigated whether the down-regulation of protein kinase C-ε (PKC-ε) is involved in the inhibition of vascular smooth muscle cell (VSMC) proliferation caused by prolonged PMA incubation. Using cell counting, Cell Counting Kit-8 (CCK-8) and EdU incorporation assay on VSMCs, we evaluated the inhibitory effects of prolonged incubation of PMA, of lentiviruses carrying the short-hairpin RNAs (shRNA) of PKC-ε and of the PKC-ε inhibitor peptide on the proliferation and viability of cells. The effect of PKC-ε down-regulation on growth of rat breast cancer SHZ-88 cells was also measured. The prolonged incubation of VSMCs with PMA for up to 72 hours resulted in attenuated cell growth rates in a time-dependent manner. The expression of PKC-ε, as assessed by Western blotting, was also decreased accordingly. Notably, the number of EdU-positive cells and the cell viability of VSMCs were decreased by shRNA of PKC-ε and the PKC-ε inhibitor peptide, respectively. The proliferation of rat breast cancer SHZ-88 cells was also attenuated by lentivirus-induced shRNA silencing of PKC-ε. Prolonged incubation of PMA can inhibit the expression of PKC-ε. The effect results in the inhibition of VSMC proliferation. PKC-ε silencing can also attenuate breast cancer cell growth, suggesting that PKC-ε may be a potential target for anti-cancer drugs. © 2016 The Author(s) Published by S. Karger AG, Basel.

Identifying the translational gap in the evaluation of drug-induced QTc interval prolongation

PubMed Central

Chain, Anne SY; Dubois, Vincent FS; Danhof, Meindert; Sturkenboom, Miriam CJM; Della Pasqua, Oscar

2013-01-01

Aims Given the similarities in QTc response between dogs and humans, dogs are used in pre-clinical cardiovascular safety studies. The objective of our investigation was to characterize the PKPD relationships and identify translational gaps across species following the administration of three compounds known to cause QTc interval prolongation, namely cisapride, d, l-sotalol and moxifloxacin. Methods Pharmacokinetic and pharmacodynamic data from experiments in conscious dogs and clinical trials were included in this analysis. First, pharmacokinetic modelling and deconvolution methods were applied to derive drug concentrations at the time of each QT measurement. A Bayesian PKPD model was then used to describe QT prolongation, allowing discrimination of drug-specific effects from other physiological factors known to alter QT interval duration. A threshold of ≥10 ms was used to explore the probability of prolongation after drug administration. Results A linear relationship was found to best describe the pro-arrhythmic effects of cisapride, d,l-sotalol and moxifloxacin both in dogs and in humans. The drug-specific parameter (slope) in dogs was statistically significantly different from humans. Despite such differences, our results show that the probability of QTc prolongation ≥10 ms in dogs nears 100% for all three compounds at the therapeutic exposure range in humans. Conclusions Our findings indicate that the slope of PKPD relationship in conscious dogs may be used as the basis for the prediction of drug-induced QTc prolongation in humans. Furthermore, the risk of QTc prolongation can be expressed in terms of the probability associated with an increase ≥10 ms, allowing direct inferences about the clinical relevance of the pro-arrhythmic potential of a molecule. PMID:23351036

The effects of nitric oxide synthase inhibitors on the sedative effect of clonidine.

PubMed

Soares de Moura, R; Rios, A A; de Oliveira, L F; Resende, A C; de Lemos Neto, M; Santos, E J; Correia, M L; Tano, T

2001-11-01

The mechanism underlying the Niteroi, Rio de Janeiro sedative effect of clonidine, an alpha2-adrenoceptor agonist, remains uncertain. Because activation of alpha2-adrenoceptors induces release of nitric oxide (NO), we tested the hypothesis that the sedative effect of clonidine depends on NO-related mechanisms. The effect of 7-nitro indazole on the sleeping time induced by clonidine was studied in Wistar rats. In addition, we examined the effect of clonidine, alpha-methyldopa, and midazolam on the thiopental-induced sleeping time in rats pretreated with N(G)-nitro-L-arginine-methyl-ester (L-NAME). The sleeping time induced by clonidine was significantly decreased by 7-nitro indazole. Thiopental sleeping time was increased by clonidine, alpha-methyldopa, and midazolam. L-NAME reduced the prolongation effect of clonidine and alpha-methyldopa, but did not alter the effect of midazolam on the thiopental-induced sleeping time. The inhibitory effect of L-NAME on clonidine-dependent prolongation of thiopental-induced sleeping time was reversed by L-arginine. These results suggest that NO-dependent mechanisms are involved in the sedative effect of clonidine. In addition, this effect seems to be specific for the sedative action of alpha2-adrenoceptors agonists. Clonidine, an antihypertensive drug, is also a sedative. This sedative effect, although an adverse event in the treatment of hypertensive patients, can be helpful for sedation of surgical patients. The mechanism of this effect, however, is unknown. In this study, we show that the sedative effect of clonidine is mediated by nitric oxide, because it could be prevented by pretreatment with nitric oxide synthase inhibitors.

Effect of prolonged stress on the adrenal hormones of individuals with irritable bowel syndrome.

PubMed

Sugaya, Nagisa; Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Nomura, Shinobu; Shimada, Hironori

2015-01-01

The purpose of this study was to investigate the effect of prolonged stress on the salivary adrenal hormones (cortisol, dehydroepiandrosterone [DHEA], DHEA-sulfate [DHEA-S]) of individuals with irritable bowel syndrome (IBS). The participants were female college students, including 10 with IBS and 16 without IBS (control group), who were scheduled for a 2-week teaching practice at a kindergarten. Participants were asked to collect saliva for determining adrenal hormones immediately and 30 min after awakening and before sleep, 2 weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. Regarding cortisol/DHEA ratio, significantly increased levels were found during the first week of the practice, and a significant interaction between group and time was found; the ratio at 30 min after awakening in the IBS group was higher than that in the control group. For the other adrenal hormone indexes, no significant differences due to the presence of IBS were found. Individuals with IBS showed an elevated cortisol/DHEA ratio after awakening compared with individuals without IBS, and the elevated ratio peaked under the prolonged stress. The present study suggests that the cortisol effect is dominant in individuals with IBS under prolonged stress.

The effect of antithyroid treatment on atrial conduction times in patients with subclinical hyperthyroidism.

PubMed

Nacar, Alper Buğra; Acar, Gürkan; Yorgun, Hikmet; Akçay, Ahmet; Özkaya, Mesut; Canpolat, Uğur; Akkoyun, Murat; Tuncer, Cemal

2012-09-01

Prolonged atrial conduction time measured by tissue Doppler imaging (TDI) has been associated with increased risk of atrial fibrillation. We aimed to evaluate the effect of subclinical hyperthyroidism (SH) and antithyroid treatment on atrial conduction time. A total of 30 patients with SH (26 females; mean age 34.8 ± 8.5 years) and 30 age- and gender-matched controls were included. Using TDI, atrial conduction time was measured from the lateral mitral annulus, septal mitral annulus, and lateral tricuspid annulus. Intra- and interatrial conduction delay were calculated. TDI and thyroid hormone levels were studied at the time of enrollment and after achievement of euthyroid state with propylthiouracil treatment. Patients were followed for 14 ± 3 weeks. Atrial conduction time at the lateral and septal mitral annulus were significantly higher in patients with SH compared to controls. Both inter-, right, and left intraatrial electromechanical delay were prolonged in patients with SH compared to control subjects (21.3 ± 6.1 vs. 13.9 ± 4.3, P < 0.001 and 4.2 ± 3.5 vs. 2.3 ± 1.9, P = 0.014 and 17.1 ± 6.0 vs. 11.6 ± 3.8, P < 0.001, respectively). After achievement of euthyroid state, inter- and left intraatrial electromechanical delay were significantly decreased compared to baseline values and approximated to the values of the control group (P < 0.001). SH is associated with prolonged atrial conduction time. After achievement of euthyroid state, decrement in atrial conduction time may reveal how the antithyroid treatment may prevent the development of atrial fibrillation in these patients. © 2012, Wiley Periodicals, Inc.

Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice.

PubMed

Wu, Chun Fu; Liu, Yan Li; Song, Ming; Liu, Wen; Wang, Jin Hui; Li, Xian; Yang, Jing Yu

2003-08-01

In the present study, pseudoginsenoside-F(11) (PF(11)), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF(11) was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF(11) did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF(11) significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF(11) greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF(11) significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF(11) could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF(11) is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

Effect of central hypothyroidism on Doppler-derived myocardial performance index.

PubMed

Doin, Fabio Luiz Casanova; Borges, Mariana da Rosa; Campos, Orlando; de Camargo Carvalho, Antonio Carlos; de Paola, Angelo Amato Vincenzo; Paiva, Marcelo Goulart; Abucham, Julio; Moises, Valdir Ambrosio

2004-06-01

Myocardial performance index (MPI) has been used to assess global ventricular function in different types of cardiac disease. Thyroid hormones influence cardiac performance directly and indirectly by changes in peripheral circulation. The aim of this study was to evaluate the possible effect of central hypothyroidism (CH) on MPI. The study included 28 control subjects and 7 patients with CH without cardiac disease. MPI was defined as the sum of isovolumetric contraction time (ICT) and isovolumetric relaxation time divided by ejection time. Patients were submitted to hormonal therapy with thyroxin and the study was repeated after 35 to 42 days. MPI was significantly higher in patients with CH (0.54 +/- 0.08) than in control subjects (0.40 +/- 0.05) (P =.002). The increase in MPI was caused by the prolongation of ICT without a significant variation of isovolumetric relaxation time and ejection time. After hormonal therapy there was a significant reduction of MPI (0.54 +/- 0.08 vs 0.42 +/- 0.07; P =.028) and ICT. MPI was increased in patients with untreated CH. The increase was related to prolongation of ICT and reverted by hormonal therapy.

An acid/alkaline stress and the addition of amino acids induce a prolonged viability of Lactobacillus plantarum loaded into alginate gel.

PubMed

Bevilacqua, Antonio; Sinigaglia, Milena; Corbo, Maria Rosaria

2010-08-15

This study reports on the investigation on the effects of the conditions used throughout the step of biomass production on the survival of Lactobacillus plantarum loaded into alginate gels. L. plantarum was grown under different conditions (MRS or a laboratory medium-LB(2)-at acidic or alkaline pHs, with NaCl, phenols, vitamins or amino acids) and immobilized in sodium alginate; cell number was evaluated throughout the storage and death (delta(stand)) and first-reduction times (delta) were calculated. The storage of alginate gels at 4 degrees C prolonged cell viability up to 60 days (ca. 20 days for cells produced in MRS and stored at 30 degrees C); however, a similar prolongation was achieved for cells produced in LB(2) adjusted to pH 5.0 and 9.0 or added with amino acids (death time>50-60 days). Copyright 2010 Elsevier B.V. All rights reserved.

Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats.

PubMed

Gadi, Dounia; Bnouham, Mohamed; Aziz, Mohammed; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Legrand, Chantal; Lafeve, Françoise Fauvel; Mekhfi, Hassane

2009-08-17

Many cardiovascular diseases are associated with an increase in blood platelet activity. In Morocco, parsley (Petroselinum crispum, Apiaceae) is one of the medicinal herbs used to treat cardiovascular diseases such as arterial hypertension. In this study, crude aqueous extract (CAE) of parsley was evaluated for its anti-platelet activity in experimental animals on platelet aggregation in vitro and ex vivo; and on bleeding time in vivo. The in vitro aggregation was monitored after pre-incubation of platelets with CAE. The bleeding time and ex vivo aggregation were performed after oral treatment. CAE inhibited dose dependently platelet aggregation in vitro induced by thrombin, ADP, collagen and epinephrine. The oral administration of CAE (3g/kg) inhibited significantly (p<0.001) platelet aggregation ex vivo and prolonged bleeding time (p<0.001) without changes in the platelet amount. The prolongation of bleeding time by CAE may be attributed to the observed inhibition of platelet aggregation. These effects could be related in part to the polyphenolic compounds present in the extract. These results support the hypothesis that the dietary intake of parsley may be benefit in the normalization of platelet hyperactivation, in the nutritional prevention of cardiovascular diseases and are potentially interesting in the development of new prevention strategies.

Method for extending the useful shelf-life of refrigerated red blood cells by flushing with inert gas

DOEpatents

Bitensky, Mark W.; Yoshida, Tatsuro

1997-01-01

Method using oxygen removal for extending the useful shelf-life of refrigerated red blood cells. A cost-effective, 4.degree. C. storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. Preservation of adenosine triphosphate levels and reduction in hemolysis and in membrane vesicle production of red blood cells stored at 4.degree. C. for prolonged periods of time is achieved by removing oxygen therefrom at the time of storage; in particular, by flushing with an inert gas. Adenosine triphosphate levels of the stored red blood cells are boosted in some samples by addition of ammonium phosphate.

Method for extending the useful shelf-life of refrigerated red blood cells by flushing with inert gas

DOEpatents

Bitensky, M.W.; Yoshida, Tatsuro

1997-04-29

A method is disclosed using oxygen removal for extending the useful shelf-life of refrigerated red blood cells. A cost-effective, 4 C storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. Preservation of adenosine triphosphate levels and reduction in hemolysis and in membrane vesicle production of red blood cells stored at 4 C for prolonged periods of time is achieved by removing oxygen from the red blood cells at the time of storage; in particular, by flushing with an inert gas. Adenosine triphosphate levels of the stored red blood cells are boosted in some samples by addition of ammonium phosphate. 4 figs.

The effects of interrupting prolonged sitting with intermittent activity on appetite sensations and subsequent food intake in preadolescent children.

PubMed

Ajibewa, Tiwaloluwa A; O'Sullivan, Molly P; Nagy, Matthew R; Block, Shannon S; Robinson, Leah E; Colabianchi, Natalie; Hasson, Rebecca E

2017-01-01

Short-term and long-term exposure to prolonged sitting is associated with excess food intake and weight gain in children. Interrupting prolonged sitting with low-intensity activity has been shown to not alter hunger, satiety, or food consumption in children, however it is unclear whether interrupting sitting with high-intensity activity will alter appetite regulation in children. The purpose of this study was to examine the acute effects of interrupting prolonged sitting with intermittent activity performed at varying intensities on hunger, satiety, prospective food consumption (PFC), and food intake in preadolescent children. Thirty-nine children (ages 7-11 years, 54% female, 33% overweight/obese) completed four experimental conditions in random order: 8 hours of sitting interrupted with 20, 2-minute low-, moderate-, or high-intensity activity breaks or 20, 2-minute sedentary screen time breaks. Exercise intensity corresponded with 25%, 50% and 75% of heart rate reserve, respectively. Hunger, satiety, and PFC were assessed using the Visual Analog Scale, at five time points (pre- and post-breakfast, pre- and post-lunch, and pre-dinner) during each experimental condition. Dietary compensation was assessed as total caloric intake during a post-condition dinner standardized to provide 70% of estimated daily energy requirements. There was a significant effect of time on hunger, satiety, and PFC throughout each condition day (p< 0.001). There were no differences across conditions for hunger (sedentary: 4.9±0.3 cm, low: 5.0±0.3 cm, moderate: 5.1±0.3 cm, high: 5.1±0.3 cm, p>0.05), satiety (sedentary: 4.7±0.3 cm, low: 4.4±0.3 cm, moderate: 4.6±0.3 cm, high: 4.2±0.3 cm, p>0.05), and PFC (sedentary: 4.9±0.3 cm, low: 4.7±0.3 cm, moderate: 4.9±0.3 cm, high: 5.0±0.3 cm, p>0.05). There were no significant differences in post-activity food intake across conditions (sedentary: 1071.9±53.6 kcals; low: 1092.6±43.4kcals; moderate: 996.2±54.6kcals; high: 1138.7±62.8kcals, p>0.05). However, there was a significant effect of condition on energy balance (sedentary: +61.4±65.9 kcals, low: +74.9±57.6 kcals, moderate: -58.3±62.8 kcals, high: -391.2±77.9 kcals; p<0.001). There were no significant effects of weight status on hunger, satiety, PFC, post-activity food intake, and mean energy balance across conditions (all p's>0.05). Interrupting prolonged sitting with physical activity of any intensity does not alter appetite sensations and subsequent food consumption in children. These data suggest that interventions targeting prolonged sitting with high-intensity intermittent activity may be an effective strategy to increase physical activity energy expenditure without increasing food intake, allowing for a short-term energy deficit in both healthy weight and overweight/obese children. Future studies should examine the long-term effects of interrupting prolonged sitting with activity on food consumption and weight status in preadolescent children.

Prolonging Microgravity on Parabolic Airplane Flights

NASA Technical Reports Server (NTRS)

Robinson, David W.

2003-01-01

Three techniques have been proposed to prolong the intervals of time available for microgravity experiments aboard airplanes flown along parabolic trajectories. Typically, a pilot strives to keep an airplane on such a trajectory during a nominal time interval as long as 25 seconds, and an experimental apparatus is released to float freely in the airplane cabin to take advantage of the microgravitational environment of the trajectory for as long as possible. It is usually not possible to maintain effective microgravity during the entire nominal time interval because random aerodynamic forces and fluctuations in pilot control inputs cause the airplane to deviate slightly from a perfect parabolic trajectory, such that the freely floating apparatus bumps into the ceiling, floor, or a wall of the airplane before the completion of the parabola.

Yerba Maté (Ilex paraguariensis) Metabolic, Satiety, and Mood State Effects at Rest and during Prolonged Exercise

PubMed Central

Alkhatib, Ahmad; Atcheson, Roisin

2017-01-01

Yerba Maté (YM), has become a popular herb ingested for enhancing metabolic health and weight-loss outcomes. No studies have tested the combined metabolic, satiety, and psychomotor effects of YM during exercise. We tested whether YM ingestion affects fatty acid oxidation (FAO), profile of mood state score (POMS), and subjective appetite scale (VAS), during prolonged moderate exercise. Twelve healthy active females were randomized to ingest either 2 g of YM or placebo (PLC) in a repeated-measures design. Participants rested for 120 min before performing a 30-min cycling exercise corresponding to individuals’ crossover point intensity (COP). FAO, determined using indirect calorimetry, was significantly higher during the 30-min exercise in YM vs. PLC (0.21 ± 0.07 vs. 0.17 ± 0.06 g/min, p < 0.05). VAS scores for hunger, prospective eating, and desire to eat were all reduced (p < 0.05). Whereas, POMS measures of focus, energy, and concentration were all increased (p < 0.05). There was no significant time-effect for any of the measured variables, nor was there any interaction effects between YM treatment and time. Combining YM intake with prolonged exercise at targeted ”fat-loss”’ intensities augments FAO and improves measures of satiety and mood state. Such positive combined metabolic, satiety, and psychomotor effects may provide an important role for designing future fat and weight-loss lifestyle interventions. PMID:28809814

Time for actions in lucid dreams: effects of task modality, length, and complexity

PubMed Central

Erlacher, Daniel; Schädlich, Melanie; Stumbrys, Tadas; Schredl, Michael

2014-01-01

The relationship between time in dreams and real time has intrigued scientists for centuries. The question if actions in dreams take the same time as in wakefulness can be tested by using lucid dreams where the dreamer is able to mark time intervals with prearranged eye movements that can be objectively identified in EOG recordings. Previous research showed an equivalence of time for counting in lucid dreams and in wakefulness (LaBerge, 1985; Erlacher and Schredl, 2004), but Erlacher and Schredl (2004) found that performing squats required about 40% more time in lucid dreams than in the waking state. To find out if the task modality, the task length, or the task complexity results in prolonged times in lucid dreams, an experiment with three different conditions was conducted. In the first condition, five proficient lucid dreamers spent one to three non-consecutive nights in the sleep laboratory. Participants counted to 10, 20, and 30 in wakefulness and in their lucid dreams. Lucidity and task intervals were time stamped with left-right-left-right eye movements. The same procedure was used for the second condition where eight lucid dreamers had to walk 10, 20, or 30 steps. In the third condition, eight lucid dreamers performed a gymnastics routine, which in the waking state lasted the same time as walking 10 steps. Again, we found that performing a motor task in a lucid dream requires more time than in wakefulness. Longer durations in the dream state were present for all three tasks, but significant differences were found only for the tasks with motor activity (walking and gymnastics). However, no difference was found for relative times (no disproportional time effects) and a more complex motor task did not result in more prolonged times. Longer durations in lucid dreams might be related to the lack of muscular feedback or slower neural processing during REM sleep. Future studies should explore factors that might be associated with prolonged durations. PMID:24474942

Time for actions in lucid dreams: effects of task modality, length, and complexity.

PubMed

Erlacher, Daniel; Schädlich, Melanie; Stumbrys, Tadas; Schredl, Michael

2013-01-01

The relationship between time in dreams and real time has intrigued scientists for centuries. The question if actions in dreams take the same time as in wakefulness can be tested by using lucid dreams where the dreamer is able to mark time intervals with prearranged eye movements that can be objectively identified in EOG recordings. Previous research showed an equivalence of time for counting in lucid dreams and in wakefulness (LaBerge, 1985; Erlacher and Schredl, 2004), but Erlacher and Schredl (2004) found that performing squats required about 40% more time in lucid dreams than in the waking state. To find out if the task modality, the task length, or the task complexity results in prolonged times in lucid dreams, an experiment with three different conditions was conducted. In the first condition, five proficient lucid dreamers spent one to three non-consecutive nights in the sleep laboratory. Participants counted to 10, 20, and 30 in wakefulness and in their lucid dreams. Lucidity and task intervals were time stamped with left-right-left-right eye movements. The same procedure was used for the second condition where eight lucid dreamers had to walk 10, 20, or 30 steps. In the third condition, eight lucid dreamers performed a gymnastics routine, which in the waking state lasted the same time as walking 10 steps. Again, we found that performing a motor task in a lucid dream requires more time than in wakefulness. Longer durations in the dream state were present for all three tasks, but significant differences were found only for the tasks with motor activity (walking and gymnastics). However, no difference was found for relative times (no disproportional time effects) and a more complex motor task did not result in more prolonged times. Longer durations in lucid dreams might be related to the lack of muscular feedback or slower neural processing during REM sleep. Future studies should explore factors that might be associated with prolonged durations.

Amphotericin B liposomes with prolonged circulation in blood: in vitro antifungal activity, toxicity, and efficacy in systemic candidiasis in leukopenic mice.

PubMed Central

van Etten, E W; ten Kate, M T; Stearne, L E; Bakker-Woudenberg, I A

1995-01-01

Pegylated amphotericin B (AmB) liposomes (PEG-AmB-LIP) were compared with laboratory-prepared nonpegylated AmB liposomes (AmB-LIP), a formulation with a lipid composition the same as that in AmBisome, as well as with industrially prepared AmBisome regarding their in vitro antifungal activities, toxicities, blood residence times, and therapeutic efficacies. Killing of Candida albicans (> 99.9%) during short-term (6-h) incubation was observed at 0.2 mg of AmB per liter for AmB desoxycholate, 0.4 mg of AmB per liter for PEG-AmB-LIP, 0.8 mg of AmB per liter for AmB-LIP, and 12.8 mg of AmB per liter for AmBisome. The maximum tolerated doses of PEG-AmB-LIP, AmB-LIP, and AmBisome were 15, 19, and > 31 mg of AmB per kg of body weight, respectively. In contrast to AmB-LIP, the blood residence time of PEG-AmB-LIP was prolonged and dose independent. In a model of systemic candidiasis in leukopenic mice at a dose of 5 mg of AmB per kg, PEG-AmB-LIP was completely effective and AmB-LIP was partially effective, whereas AmBisome was not effective. AmB-LIP at 11 mg of AmB per kg was partially effective. AmBisome at 29 mg of AmB per kg was completely effective. In conclusion, the therapeutic efficacies of AmB liposomes can be improved by preparing AmB liposomes in which a substantial reduction in toxicity is achieved while antifungal activity is retained. In addition, therapeutic efficacy is favored by a prolonged residence time of AmB liposomes in blood. PMID:8540697

Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling

PubMed Central

Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Cenglin; Wang, Yi; Dai, Yunjian; Wu, Dengchang; Zhu, Junmin; Wang, Shuang; Zhou, Yudong; Shi, Liyun; Hu, Weiwei; Zhang, Xia; Chen, Zhong

2016-01-01

It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS. PMID:26902320

Prolonged particulate chromate exposure does not inhibit homologous recombination repair in North Atlantic right whale (Eubalaena glacialis) lung cells.

PubMed

Browning, Cynthia L; Wise, Catherine F; Wise, John Pierce

2017-09-15

Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability. Thus, the goal of this study was to determine the effect of prolonged Cr(VI) exposure on HR repair and clastogenesis in North Atlantic right whale (Eubalaena glacialis) lung cells. We show particulate Cr(VI) induces HR repair activity after both acute (24h) and prolonged (120h) exposure in North Atlantic right whale cells. Although the RAD51 response was lower following prolonged Cr(VI) exposure compared to acute exposure, the response was sufficient for HR repair to occur. In accordance with active HR repair, no increase in Cr(VI)-induced clastogenesis was observed with increased exposure time. These results suggest prolonged Cr(VI) exposure affects HR repair and genomic stability differently in whale and human lung cells. Future investigation of the differences in how human and whale cells respond to chemical carcinogens may provide valuable insight into mechanisms of preventing chemical carcinogenesis. Copyright © 2017. Published by Elsevier Inc.

Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity

PubMed Central

Pereira, Sandra; Yu, Wen Qin; Frigolet, María E; Beaudry, Jacqueline L; Shpilberg, Yaniv; Park, Edward; Dirlea, Cristina; Nyomba, B L Grégoire; Riddell, Michael C; Fantus, I George; Giacca, Adria

2013-01-01

We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase. PMID:23328071

Prolonged and continuous antibacterial and anti-biofilm activities of thin films embedded with gentamicin-loaded mesoporous silica nanoparticles

NASA Astrophysics Data System (ADS)

Tamanna, Tasnuva; Landersdorfer, Cornelia B.; Ng, Hooi Jun; Bulitta, Jürgen B.; Wood, Peter; Yu, Aimin

2018-05-01

The application of mesoporous silica nanoparticles (MSNs) in drug delivery systems has become highly attractive since the early 2000s. In this study, thin-film coatings embedded with gentamicin-loaded mesoporous silica nanoparticles (MSN-G) were prepared to provide antibacterial and anti-biofilm activity over a prolonged period of time. The prolonged and continuous activity of MSN-G films against Staphylococcus aureus throughout the release period was studied via two methods, namely, (1) disc diffusion of released gentamicin and (2) by shifting the MSN-G thin film to a new agar plate at certain time intervals. The expansion of the inhibition zone from 4.6 ± 0.5 to 9.7 ± 0.5 mm as caused by the released fraction of gentamicin from the first week to the eighth week indicated the controlled and slow release behaviour of loaded antibiotic and prolonged antibacterial efficacy of these films. In addition, the appearance of an inhibition zone after each shifting of the film to a new agar plate was persistent up to 103 days which confirmed that thin films successively prevented bacterial growth over a long period of time. In addition, the anti-biofilm activity of MSN-G films was evaluated by imaging bacterial cells attachment via confocal laser scanning microscopy and scanning electron microscopy. Remarkably, the anti-biofilm performance remained active for more than 2 months. To the best of our knowledge, such a slow and controlled release of antibiotic from nanoparticle embedded thin films with uninterrupted, continuous, and prolonged antibacterial effect for more than 2 months has not been reported yet.

Increased mean time from end of surgery to operating room exit in a historical cohort of cases with prolonged time to extubation.

PubMed

Dexter, Franklin; Epstein, Richard H

2013-12-01

Prolonged time to extubation has been defined as the occurrence of a ≥ 15-minute interval from the end of surgery to removal of the tracheal tube. We quantified the increases in the mean times from end of surgery to exit from the OR associated with prolonged extubations and tested whether the increases were economically important (≥ 5 minutes). Anesthesia information management system data from 1 tertiary hospital were collected from November 2005 through December 2012 (i.e., sample sizes were N = 22 sequential quarters). Cases were excluded in which the patient's trachea was not intubated or extubated while physically in the operating room (OR). For each combination of stratification variable (below) and quarter, the mean time from end of surgery to OR exit was calculated for the extubations that were not prolonged and for those that were prolonged. Results are reported as mean ± SEM, with "at least" denoting the lower 95% confidence interval. The mean times from end of surgery to OR exit were at least 12.6 minutes longer for prolonged extubations when calculated with stratification by duration of surgery and prone or other positioning (13.0 ± 0.1 minutes), P < 0.0001 compared to 5 minutes (i.e., times were substantively long economically). The mean times were at least 11.7 minutes longer when calculated stratified by anesthesia procedure code (12.4 ± 0.4, P < 0.0001) and at least 11.3 minutes longer when calculated stratified by surgeon (12.4 ± 0.6, P < 0.0001). We recommend that anesthesia providers document the times of extubations and monitor the incidence of prolonged extubations as an economic measure. This would be especially important for providers at facilities with many ORs that have at least 8 hours of cases and turnovers.

Increased Late Sodium Current Contributes to the Electrophysiological Effects of Chronic, but Not Acute, Dofetilide Administration.

PubMed

Qiu, Xiaoliang S; Chauveau, Samuel; Anyukhovsky, Evgeny P; Rahim, Tania; Jiang, Ya-Ping; Harleton, Erin; Feinmark, Steven J; Lin, Richard Z; Coronel, Ruben; Janse, Michiel J; Opthof, Tobias; Rosen, Tove S; Cohen, Ira S; Rosen, Michael R

2016-04-01

Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized that chronic dofetilide administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. We continuously infused dofetilide (6-9 μg/kg bolus+6-9 μg/kg per hour IV infusion) into anesthetized dogs for 7 hours, maintaining plasma levels within the therapeutic range. In separate experiments, myocardial biopsies were taken before and during 6-hour intravenous dofetide infusion, and the level of phospho-Akt was determined. Acute and chronic dofetilide effects on action potential duration (APD) were studied in canine left ventricular subendocardial slabs using microelectrode techniques. Dofetilide monotonically increased QTc and APD throughout 6.5-hour exposure. Dofetilide infusion during ≥210 minutes inhibited Akt phosphorylation. INa-L block with lidocaine shortened QTc and APD more at 6.5 hours than at 50 minutes (QTc) or 30 minutes (APD) dofetilide administration. In comparison, moxifloxacin, an IKr blocker with no effects on phosphoinositide 3-kinase and INa-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion. Lidocaine shortened APD equally during acute and chronic moxifloxacin superfusion. Increased INa-L contributes to chronic dofetilide effects in vivo. These data emphasize the need to include time and INa-L in evaluating the phosphoinositide 3-kinase inhibition-derived proarrhythmic potential of drugs and provide a mechanism for benefit from lidocaine administration in clinical acquired long QT syndrome. © 2016 American Heart Association, Inc.

Survival of Listeria monocytogenes and Staphylococcus aureus in Synthetic Brines. Studying the Effects of Salt, Temperature and Sugar through the Approach of the Design of Experiments

PubMed Central

Bevilacqua, Antonio; Campaniello, Daniela; Speranza, Barbara; Sinigaglia, Milena; Corbo, Maria R.

2018-01-01

The fermentation of table olives relies on a complex microbiota of lactic acid bacteria (LAB), yeasts, and enterobacteria. Producers often add sugar to increase the growth rate of LAB, “but this practice could also increase the survival rate of some pathogens. Therefore, the main topic of this paper was to study the effect of sugar, salt and temperature on the survival of Staphylococcus aureus and Listeria monocytogenes in a synthetic brine through the theory of the Design of Experiments (simplex centroid). The addition of sugar could prolong the survival time of L. monocytogenes by 40 days, whereas an increase of the temperature caused a decrease of survival from 18 to 3 days. The survival time of S. aureus was prolonged by 50 days by combining sugar (2–4 g/l) and low temperatures (5–15°C). The use of desirability approach and prediction profiles suggests that the prolongation of the survival time of L. monocytogenes could be related to a shift in the geometrical shape of the death kinetic. This paper offers a structured statistical approach on the variables acting on the survival of two pathogens in brines and represents the first step to set up and design a predictive approach for olive producers. PMID:29497414

Acidosis slows electrical conduction through the atrio-ventricular node

PubMed Central

Nisbet, Ashley M.; Burton, Francis L.; Walker, Nicola L.; Craig, Margaret A.; Cheng, Hongwei; Hancox, Jules C.; Orchard, Clive H.; Smith, Godfrey L.

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis. PMID:25009505

Acidosis slows electrical conduction through the atrio-ventricular node.

PubMed

Nisbet, Ashley M; Burton, Francis L; Walker, Nicola L; Craig, Margaret A; Cheng, Hongwei; Hancox, Jules C; Orchard, Clive H; Smith, Godfrey L

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

The effect of acute pre-exercise dark chocolate consumption on plasma antioxidant status, oxidative stress and immunoendocrine responses to prolonged exercise.

PubMed

Davison, Glen; Callister, Robin; Williamson, Gary; Cooper, Karen A; Gleeson, Michael

2012-02-01

Acute antioxidant supplementation may modulate oxidative stress and some immune perturbations that typically occur following prolonged exercise. The aims of the present study were to examine the effects of acutely consuming dark chocolate (high polyphenol content) on plasma antioxidant capacity, markers of oxidative stress and immunoendocrine responses to prolonged exercise. Fourteen healthy men cycled for 2.5 h at ~60% maximal oxygen uptake 2 h after consuming 100 g dark chocolate (DC), an isomacronutrient control bar (CC) or neither (BL) in a randomised-counterbalanced design. DC enhanced pre-exercise antioxidant status (P = 0.003) and reduced by trend (P = 0.088) 1 h post-exercise plasma free [F₂-isoprostane] compared with CC (also, [F₂-isoprostane] increased post-exercise in CC and BL but not DC trials). Plasma insulin concentration was significantly higher pre-exercise (P = 0.012) and 1 h post-exercise (P = 0.026) in the DC compared with the CC trial. There was a better maintenance of plasma glucose concentration on the DC trial (2-way ANOVA trial × time interaction P = 0.001), which decreased post-exercise in all trials but was significantly higher 1 h post-exercise (P = 0.039) in the DC trial. There were no between trial differences in the temporal responses (trial × time interactions all P > 0.05) of hypothalamic-pituitary-adrenal axis stress hormones, plasma interleukin-6, the magnitude of leukocytosis and neutrophilia and changes in neutrophil function. Acute DC consumption may affect insulin, glucose, antioxidant status and oxidative stress responses, but has minimal effects on immunoendocrine responses, to prolonged exercise.

The Potential Impact of Displacing Sedentary Time in Adults with Type 2 Diabetes

PubMed Central

FALCONER, CATHERINE L.; PAGE, ANGIE S.; ANDREWS, ROB C.; COOPER, ASHLEY R.

2015-01-01

ABSTRACT Purpose Sedentary time, in particular, prolonged unbroken sedentary time, is detrimental to health and displaces time spent in either light or moderate intensity physical activity. This cross-sectional study aimed to identify the potential impact of reallocating time from sedentary behaviors to more active behaviors on measures of body composition and metabolic health in people with type 2 diabetes. Methods Participants were 519 adults with newly diagnosed type 2 diabetes who had been recruited to the Early Activity in Diabetes (Early ACTID) randomized controlled trial. Waist-worn accelerometers were used to obtain objective measurement of sedentary time, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) at baseline alongside clinical measurements and fasting blood samples to determine cholesterol, triglycerides, HOMA-IR, and glucose. Isotemporal substitution modeling was performed to determine the potential impact of reallocating 30 min of sedentary time accumulated in a single bout (long bout) with 30 min of interrupted sedentary time, LPA, or MVPA. Results Sedentary time accounted for 65% of the waking day, of which 45% was accumulated in prolonged (≥30 min) bouts. Reallocation of 30 min of long-bout sedentary time with 30 min of short-bout sedentary time was associated with lower body mass index (BMI) (adjusted β, −0.60; 95% confidence interval [CI], −1.00, −0.21) and waist circumference (WC) (adjusted β, −1.16; 95% CI, −2.08, −0.25). Stronger effects were seen for LPA and MVPA. Reallocation of 30 min of long-bout sedentary time with LPA was associated with higher HDL-cholesterol (adjusted β, 0.02; 95% CI, 0.00–0.03 mmol·L−1). Conclusions Encouraging adults with newly diagnosed type 2 diabetes to break up prolonged periods of sedentary time may be an effective strategy for improving body composition and metabolic health. PMID:26378943

Delayed Post-ischemic Conditioning Significantly Improves the Outcome after Retinal Ischemia

PubMed Central

Dreixler, John C.; Poston, Jacqueline N.; Shaikh, Afzhal R.; Alexander, Michael; Tupper, Kelsey Y.; Marcet, Marcus M.; Bernaudin, Myriam; Roth, Steven

2011-01-01

In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. These studies showed that post-conditioning effectively prevented damage after retinal ischemia when it was instituted early (within one hour) in the post-ischemic period. While post-ischemic conditioning holds high promise of clinical translation, patients often present late after the onset of retinal ischemia and therefore immediate application of this anti-ischemic maneuver is generally not feasible. In this study, we examined the hypothesis that application of a post-conditioning stimulus at 24 h or greater following the end of prolonged ischemia would decrease the extent of ischemic injury. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 5 minutes of post-conditioning brief ischemia 24 or 48 h after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia and post-conditioning or sham post-conditioning. We found that the brief ischemic stimulus applied 24, but not 48 h after prolonged ischemia significantly improved functional recovery and decreased histological damage induced by prolonged ischemia. We conclude that within a defined time window, delayed post-ischemic conditioning ameliorated post-ischemic injury in rats. Compared to earlier studies, the present work demonstrates for the first time the novel ability of a significantly delayed ischemic stimulus to provide robust neuroprotection in the retina following ischemia. PMID:21501608

Reaction time in pilots at sustained acceleration of +4.5 G(z).

PubMed

Truszczynski, Olaf; Wojtkowiak, Mieczyslaw; Lewkowicz, Rafal; Biernacki, Marcin P; Kowalczuk, Krzysztof

2013-08-01

Pilots flying at very high speed are exposed to the effects of prolonged accelerations while changing their flight path. The aim of this research was to assess the impact of sustained accelerations on the visual-motor response times of pilots and the acceleration tolerance level (ATL) as a measure of pilots' endurance to applied +G(z). The study involved 18 young pilots, 23-25 yr of age. The subjects' task was to quickly and accurately respond to the light stimuli presented on a light bar during exposure to acceleration at +4.5 G(z) and until reaching the ATL. Simple response time (SRT) measurements were performed using a visual-motor analysis system throughout the exposures, which allowed the assessment of a pilot's ATL. The pilots' ATL ranged from 270 to 366 s (Mean = 317.7 +/- 26.15 SD). The analysis of the SRT indicated a significant effect of duration of acceleration on the visual response time. The results of the post hoc comparisons showed that SRT increased with longer durations of the same level of +G(z) load and then decreased, reaching values similar to the controls. Exposure to prolonged acceleration of +4.5 G(z) significantly increases SRT. There was no statistically significant difference in SRT between the pilots with "short" and "long" time exposures. A pilot's SRT during a prolonged +4.5 G(z) exposure could be a reliable indicator of pilot G performance in the fast jet. Deterioration of SRT may be used to predict imminent +G(z) endurance limits between pilots with widely varying endurance abilities.

The effects of temperament, character, and defense mechanisms on grief severity among the elderly.

PubMed

Gana, Kamel; K'Delant, Pascaline

2011-01-01

The aims of this study were to examine the relationships between Cloninger's psychobiological model of personality, defense styles, and severity of grief, and to identify the influential temperament and character dimensions that differentiate subjects with prolonged grief from those without prolonged grief. A sample of 72 bereaved elderly persons for whom the loss of a loved one occurred on average 2.58 years (SD = 1.92) prior to participation in this study were assessed using the Inventory of Complicated Grief-Revised, the Temperament and Character Inventory, and the Defense Styles Questionnaire. Using the algorithm developed by Prigerson et al. (2009) for diagnosing prolonged grief, 18 of our participants were identified as having this disorder. A multiple regression analysis revealed that time since loss, persistence, an immature defense style, and the age of the bereaved person positively predicted severity of grief, whereas cooperativeness and the age of the deceased loved one negatively predicted severity of grief. A binary logistic regression showed that gender, a close kinship relation to the deceased, time since loss, self-directedness (SD), and self-transcendence (ST) were predictors of prolonged grief, whereas the age of the deceased and cooperativeness (CO) were negatively related to prolonged grief. Our sample was small. Self-report measures of grief were not supplemented with clinical evaluation. Our results suggest that only character dimensions (high SD and ST, and low CO) are involved in the psychopathology of prolonged grief. Also, according to Cloninger's character cube (Cloninger, 2004), high SD and ST scores, and low CO scores are indicative of a fanatical character. Copyright © 2010 Elsevier B.V. All rights reserved.

Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress.

PubMed

Zou, Yingxin; Liu, Yuxiang; Ruan, Minghua; Feng, Xu; Wang, Jiachun; Chu, Zhiyong; Zhang, Zesheng

2015-10-01

This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process.

Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress

PubMed Central

ZOU, YINGXIN; LIU, YUXIANG; RUAN, MINGHUA; FENG, XU; WANG, JIACHUN; CHU, ZHIYONG; ZHANG, ZESHENG

2015-01-01

This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process. PMID:26239097

Is Exposure Necessary? A Randomized Clinical Trial of Interpersonal Psychotherapy for PTSD

PubMed Central

Markowitz, John C.; Petkova, Eva; Neria, Yuval; Van Meter, Page E.; Zhao, Yihong; Hembree, Elizabeth; Lovell, Karina; Biyanova, Tatyana; Marshall, Randall D.

2015-01-01

Background Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). No treatment benefits all patients, however. We tested Interpersonal Psychotherapy, which has demonstrated antidepressant efficacy and showed promise in pilot PTSD research, as a non-exposure-based, non-cognitive behavioral PTSD treatment. Methods A randomized, fourteen-week trial compared Interpersonal Psychotherapy; Prolonged Exposure, an exposure-based exemplar; and Relaxation Therapy, an active control psychotherapy. Subjects were 110 unmedicated patients having DSM-IV chronic PTSD and Clinician-Administered PTSD Scale (CAPS) score >50. Randomization stratified for comorbid major depression. We hypothesized Interpersonal Psychotherapy would be no more than minimally inferior (CAPS difference <12.5 points) to Prolonged Exposure. Results All therapies had large within-group pre/post effect sizes (d=1.32–1.88). Response rates (>30% CAPS improvement) were: Interpersonal Psychotherapy 63%, Prolonged Exposure 47%, Relaxation Therapy 38% (n.s.). Interpersonal psychotherapy and Prolonged Exposure CAPS outcome differed by 5.5 points (n.s.); the null hypothesis of more than minimal Interpersonal Psychotherapy inferiority was rejected (p=0.035). Patients with comorbid major depression dropped out from Prolonged Exposure nine times more than non-depressed Prolonged Exposure patients. Interpersonal Psychotherapy and Prolonged Exposure improved quality of life and social functioning more than Relaxation Therapy. Conclusions This first controlled study of individual Interpersonal Psychotherapy for PTSD demonstrated non-inferiority to the “gold standard” PTSD treatment. Interpersonal Psychotherapy had (non-significantly) lower attrition and higher response rates than Prolonged Exposure. Contradicting a widespread clinical belief, PTSD treatment may not require cognitive behavioral exposure to trauma reminders. Moreover, as differential therapeutics, patients with comorbid major depression may fare better in Interpersonal Psychotherapy than Prolonged Exposure. PMID:25677355

Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong

NASA Astrophysics Data System (ADS)

Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward

2017-11-01

Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights imply the need to categorize prolonged heat for public health surveillance. Findings also contribute to potential improvement to existing heat-health warning system.

Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong.

PubMed

Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward

2017-11-01

Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights imply the need to categorize prolonged heat for public health surveillance. Findings also contribute to potential improvement to existing heat-health warning system.

Neuromuscular pharmacodynamics of mivacurium in adults with major burns.

PubMed

Han, T-H; Martyn, J A J

2011-05-01

Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different. The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

Mitigating prolonged QT interval in cancer nanodrug development for accelerated clinical translation.

PubMed

Ranjan, Amalendu P; Mukerjee, Anindita; Helson, Lawrence; Vishwanatha, Jamboor K

2013-12-14

Cardiac toxicity is the foremost reason for drug discontinuation from development to clinical evaluation and post market surveillance [Fung 35:293-317, 2001; Piccini 158:317-326 2009]. The Food and Drug Administration (FDA) has rejected many potential pharmaceutical agents due to QT prolongation effects. Since drug development and FDA approval takes an enormous amount of time, money and effort with high failure rates, there is an increased focus on rescuing drugs that cause QT prolongation. If these otherwise safe and potent drugs were formulated in a unique way so as to mitigate the QT prolongation associated with them, these potent drugs may get FDA approval for clinical use. Rescuing these compounds not only benefit the patients who need them but also require much less time and money thus leading to faster clinical translation. In this study, we chose curcumin as our drug of choice since it has been shown to posses anti-tumor properties against various cancers with limited toxicity. The major limitations with this pharmacologically active drug are (a) its ability to prolong QT by inhibiting the hERG channel and (b) its low bioavailability. In our previous studies, we found that lipids have protective actions against hERG channel inhibition and therefore QT prolongation. Results of the manual patch clamp assay of HEK 293 cells clearly illustrated that our hybrid nanocurcumin formulation prevented the curcumin induced inhibition of hERG K+ channel at concentrations higher than the therapeutic concentrations of curcumin. Comparing the percent inhibition, the hybrid nanocurcumin limited inhibition to 24.8% at a high curcumin equivalent concentration of 18 μM. Liposomal curcumin could only decrease this inhibition upto 30% only at lower curcumin concentration of 6 μM but not at 18 μM concentration. Here we show a curcumin encapsulated lipopolymeric hybrid nanoparticle formulation which could protect against QT prolongation and also render increased bioavailability and stability thereby overcoming the limitations associated with curcumin.

Left Ventricular Isovolumetric Relaxation Time Is Prolonged in Fetal Long-QT Syndrome.

PubMed

Clur, Sally-Ann B; Vink, Arja S; Etheridge, Susan P; Robles de Medina, Pascale G; Rydberg, Annika; Ackerman, Michael J; Wilde, Arthur A; Blom, Nico A; Benson, D Woodrow; Herberg, Ulrike; Donofrio, Mary T; Cuneo, Bettina F

2018-04-01

Long-QT syndrome (LQTS), an inherited cardiac repolarization disorder, is an important cause of fetal and neonatal mortality. Detecting LQTS prenatally is challenging. A fetal heart rate (FHR) less than third percentile for gestational age is specific for LQTS, but the sensitivity is only ≈50%. Left ventricular isovolumetric relaxation time (LVIRT) was evaluated as a potential diagnostic marker for fetal LQTS. LV isovolumetric contraction time, LV ejection time, LVIRT, cycle length, and FHR were measured using pulsed Doppler waveforms in fetuses. Time intervals were expressed as percentages of cycle length, and the LV myocardial performance index was calculated. Single measurements were stratified by gestational age and compared between LQTS fetuses and controls. Receiver-operator curves were performed for FHR and normalized LVIRT (N-LVIRT). A linear mixed-effect model including multiple measurements was used to analyze trends in FHR, N-LVIRT, and LV myocardial performance index. There were 33 LQTS fetuses and 469 controls included. In LQTS fetuses, the LVIRT was prolonged in all gestational age groups ( P <0.001), as was the N-LVIRT. The best cutoff to diagnose LQTS was N-LVIRT ≥11.3 at ≤20 weeks (92% sensitivity, 70% specificity). Simultaneous analysis of N-LVIRT and FHR improved the sensitivity and specificity for LQTS (area under the curve=0.96; 95% confidence interval, 0.82-1.00 at 21-30 weeks). N-LVIRT, LV myocardial performance index, and FHR trends differed significantly between LQTS fetuses and controls through gestation. The LVIRT is prolonged in LQTS fetuses. Findings of a prolonged N-LVIRT and sinus bradycardia can improve the prenatal detection of fetal LQTS. © 2018 American Heart Association, Inc.

Cost savings from peritoneal dialysis therapy time extension using icodextrin.

PubMed

Johnson, David W; Vincent, Kaia; Blizzard, Sophie; Rumpsfeld, Markus; Just, Paul

2003-01-01

Previous retrospective studies have reported that icodextrin may prolong peritoneal dialysis (PD) treatment time in patients with refractory fluid overload (RFO). Because the annual cost of PD therapy is lower than that of hemodialysis (HD) therapy in Australia, we prospectively investigated the ability of icodextrin to prolong PD technique survival in patients with RFO. We used a computer model to estimate the savings associated with that therapeutic strategy, based on annual therapy costs determined in a regional PD and HD costing exercise. Patients who met standard criteria for RFO and who were otherwise to be converted immediately to HD, were asked to consent to an open-label assessment of the ability of icodextrin to delay the need to start HD. Time to conversion to HD was measured. The study enrolled 39 patients who were followed for a mean period of 1.1 years. Icodextrin significantly increased peritoneal ultrafiltration by a median value of 368 mL daily. It prolonged technique survival by a mean period of 1.21 years [95% confidence interval (CI): 0.80-1.62 years]. Extension of PD treatment time by icodextrin was particularly marked for patients who had ultrafiltration failure (UFF, n = 20), defined as net daily peritoneal ultrafiltration < 1 L daily (mean extension time: 1.70 years; 95% CI: 1.16-2.25 years). Overall, annualized savings were US$3,683 per patient per year. If just the patients with UFF were considered, the savings increased to US$4,893 per year. Icodextrin prolongs PD technique survival in patients with RFO, permitting them to continue on their preferred therapy. In Australia, that practice is highly cost-effective, particularly in individuals with UFF.

Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cros, C., E-mail: caroline.cros@hotmail.co.uk; Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com; Moors, J.

Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau ofmore » each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three antiarrhythmics were enhanced. ► Detection of a drug-induced prolongation of QRS was improved at high heart rate.« less

Inhibitory Effects of Medium Molecular Weight Heparinyl Amino Acid Derivatives on Ischemic Paw Edema in Mice.

PubMed

Takeda, Seiichi; Toda, Takao; Nakamura, Kazuki

2016-01-01

We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Structural characterization of coagulant Moringa oleifera Lectin and its effect on hemostatic parameters.

PubMed

Luz, Luciana de Andrade; Silva, Mariana Cristina Cabral; Ferreira, Rodrigo da Silva; Santana, Lucimeire Aparecida; Silva-Lucca, Rosemeire Aparecida; Mentele, Reinhard; Oliva, Maria Luiza Vilela; Paiva, Patricia Maria Guedes; Coelho, Luana Cassandra Breitenbach Barroso

2013-07-01

Lectins are carbohydrate recognition proteins. cMoL, a coagulant Moringa oleifera Lectin, was isolated from seeds of the plant. Structural studies revealed a heat-stable and pH resistant protein with 101 amino acids, 11.67 theoretical pI and 81% similarity with a M. oleifera flocculent protein. Secondary structure content was estimated as 46% α-helix, 12% β-sheets, 17% β-turns and 25% unordered structures belonging to the α/β tertiary structure class. cMoL significantly prolonged the time required for blood coagulation, activated partial thromboplastin (aPTT) and prothrombin times (PT), but was not so effective in prolonging aPTT in asialofetuin presence. cMoL acted as an anticoagulant protein on in vitro blood coagulation parameters and at least on aPTT, the lectin interacted through the carbohydrate recognition domain. Copyright © 2013 Elsevier B.V. All rights reserved.

Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge Behavior and Force Generation in Failing Human Myocardium.

PubMed

Mamidi, Ranganath; Li, Jiayang; Gresham, Kenneth S; Verma, Sujeet; Doh, Chang Yoon; Li, Amy; Lal, Sean; Dos Remedios, Cristobal G; Stelzer, Julian E

2017-10-01

Omecamtiv mecarbil (OM) enhances systolic function in vivo by directly binding the myosin cross-bridges (XBs) in the sarcomere. However, the mechanistic details governing OM-induced modulation of XB behavior in failing human myocardium are unclear. The effects of OM on steady state and dynamic XB behavior were measured in chemically skinned myocardial preparations isolated from human donor and heart failure (HF) left ventricle. HF myocardium exhibited impaired contractile function as evidenced by reduced maximal force, magnitude of XB recruitment ( P df ), and a slowed rate of XB detachment ( k rel ) at submaximal Ca 2+ activations. Ca 2+ sensitivity of force generation (pCa 50 ) was higher in HF myocardium when compared with donor myocardium, both prior to and after OM incubations. OM incubation (0.5 and 1.0 μmol/L) enhanced force generation at submaximal Ca 2+ activations in a dose-dependent manner. Notably, OM induced a slowing in k rel with 1.0 μmol/L OM but not with 0.5 μmol/L OM in HF myocardium. Additionally, OM exerted other differential effects on XB behavior in HF myocardium as evidenced by a greater enhancement in P df and slowing in the time course of cooperative XB recruitment ( T rec ), which collectively prolonged achievement of peak force development ( T pk ), compared with donor myocardium. Our findings demonstrate that OM augments force generation but also prolongs the time course of XB transitions to force-bearing states in remodeled HF myocardium, which may extend the systolic ejection time in vivo. Optimal OM dosing is critical for eliciting enhanced systolic function without excessive prolongation of systolic ejection time, which may compromise diastolic filling. © 2017 American Heart Association, Inc.

An unusual case of prolonged post-endoscopic retrograde cholangiopancreatography jaundice.

PubMed

Tziatzios, Georgios; Gkolfakis, Paraskevas; Papanikolaou, Ioannis S; Dimitriadis, George; Triantafyllou, Konstantinos

2016-04-01

Despite the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of choledocholithiasis, various complications have been described. We herein report the first case of prolonged post-ERCP jaundice due to toxicity of the contrast agent Iobitridol (®XENETIX, Guerbet, Roissy CdG Cedex, France) in a patient who underwent ERCP with sphincterectomy and common bile duct stone removal. While clinical improvement and normalization of aminotransferases and cholestatic enzymes after the procedure, an unexplained increase of direct bilirubin was noticed. A second ERCP was performed one week later, excluding possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin increased further up to 15 mg/dL. Other potential causes of direct hyperbilirubinemia were ruled out and patient's liver biopsy was compatible with drug-induced liver toxicity. Additionally, the cause-result time connection between the use of Iobitridol and bilirubin increase indicated the possibility of a toxic effect related to the repeated use of the particular contrast agent. Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia.

Effects of prolonged wakefulness combined with alcohol and hands-free cell phone divided attention tasks on simulated driving.

PubMed

Iudice, A; Bonanni, E; Gelli, A; Frittelli, C; Iudice, G; Cignoni, F; Ghicopulos, I; Murri, L

2005-03-01

Simulated driving ability was assessed following administration of alcohol, at an estimated blood level of 0.05%, and combined prolonged wakefulness, while participants were undertaking divided attention tasks over a hands-free mobile phone. Divided attention tasks were structured to provide a sustained cognitive workload to the subjects. Twenty three young healthy individuals drove 10 km simulated driving under four conditions in a counterbalanced, within-subject design: alcohol, alcohol and 19 h wakefulness, alcohol and 24 h wakefulness, and while sober. Study measures were: simulated driving, self-reported sleepiness, critical flicker fusion threshold (CFFT), Stroop word-colour interference test (Stroop) and simple visual reaction times (SVRT). As expected, subjective sleepiness was highly correlated with both sleep restriction and alcohol consumption. The combination of alcohol and 24 h sustained wakefulness produced the highest driving impairment, significantly beyond the alcohol effect itself. Concurrent alcohol and 19 h wakefulness significantly affected only driving time-to-collision. No significant changes of study measures occurred following alcohol intake in unrestricted sleep conditions. CFFT, SVRT and Stroop results showed a similar trend in the four study conditions. Thus apparently 'safe' blood alcohol levels in combination with prolonged wakefulness resulted in significant driving impairments. In normal sleep conditions alcohol effects on driving were partially counteracted by the concomitant hands-free phone based psychometric tasks. 2005 John Wiley & Sons, Ltd.

Temporal profile of prolonged, night-time driving performance: breaks from driving temporarily reduce time-on-task fatigue but not sleepiness.

PubMed

Phipps-Nelson, Jo; Redman, Jennifer R; Rajaratnam, Shantha M W

2011-09-01

Breaks are often used by drivers to counteract sleepiness and time-on-task fatigue during prolonged driving. We examined the temporal profile of changes in driving performance, electroencephalogram (EEG) activity and subjective measures of sleepiness and fatigue during prolonged nocturnal driving in a car simulator. In addition, the study examined the impact of regular breaks from driving on performance, sleepiness and fatigue. Healthy volunteers (n=12, 23-45 years) maintained a regular sleep-wake pattern for 14 days and were then in a laboratory from 21:00 to 08:30 hours. The driving simulator scene was designed to simulate monotonous night-time rural driving. Participants drove 4 × 2-h test sessions, with a break from driving of 1 h between each session. During the break participants performed tests assessing sleepiness and fatigue, and psychomotor performance (~30 mins), and then were permitted to sit quietly. They were monitored for wakefulness, and not permitted to nap or ingest caffeine. EEG was recorded during the driving task, and subjective assessments of sleepiness and fatigue were obtained at the start and completion of each session. We found that driving performance deteriorated (2.5-fold), EEG delta, theta and alpha activity increased, and subjective sleepiness and fatigue ratings increased across the testing period. Driving performance and fatigue ratings improved following the scheduled breaks from driving, while the breaks did not affect EEG activity and subjective sleepiness. Time-on-task effects increased through the testing period, indicating that these effects are exacerbated by increasing sleepiness. Breaks from driving without sleep temporarily ameliorate time-on-task fatigue, but provide little benefit to the sleepy driver. © 2010 European Sleep Research Society.

Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin.

PubMed

Tawara, Shunsuke; Sakai, Takumi; Matsuzaki, Osamu

2016-11-01

Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro. CPB2 activity and tissue factor-induced thrombin generation was examined by a chromogenic assay. C5a inactivation was evaluated by C-terminal cleavage of C5a and inhibition of C5a-induced human neutrophil migration. Clot lysis time prolongation was examined by a tissue-type plasminogen activator-induced clot lysis assay. CPB2 activity in human plasma was increased by TM alfa and thrombin in a concentration-dependent manner. TM alfa inhibited tissue factor-induced thrombin generation and enhanced pro-CPB2 activation in human plasma simultaneously. The mass spectrum of C5a treated with TM alfa, thrombin, and pro-CPB2 was decreased at 156m/z, indicating that TM alfa enhanced the processing of C5a to C-terminal-cleaved C5a, an inactive form of C5a. C5a-induced human neutrophil migration was decreased after C5a treatment with TM alfa, thrombin, and pro-CPB2. TM alfa prolonged the clot lysis time in human plasma, and this effect was completely abolished by addition of a CPB2 inhibitor. TM alfa exerts anti-inflammatory and anti-fibrinolytic effects through CPB2 in the presence of thrombin in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prolonged neurophysiologic effects of levetiracetam after oral administration in humans.

PubMed

Epstein, Charles M; Girard-Siqueira, Lhys; Ehrenberg, Joshua Andrew

2008-07-01

To determine whether neurophysiological effects of levetiracetam (LEV) outlast its serum half-life of approximately 7 h. Demonstration of prolonged effects would help to explain the efficacy of LEV at conventional dosing intervals that are longer than the serum half-life. Following an oral dose of LEV 3 g in 12 normal volunteers, we compared transcranial magnetic stimulation (TMS) measures of motor threshold (MT) and recruitment with LEV serum levels and subjective ratings of toxicity over 48 h. Subjects used a two-dimensional visual-analog scale to estimate the time course of any side effects. LEV serum levels and subjective toxicity both peaked around 1 h after oral administration. MT elevation was delayed in comparison to peak serum levels and subjective toxicity. MT was maximally elevated at 6-9 h, and recruitment maximally reduced at 0.6-9 h. Changes in both measures had recovered by approximately 50% at 24 h. Despite the time difference between toxicity and TMS changes, toxicity estimates correlated with the maximum increase in MT. There is a substantial time lag between LEV serum levels and TMS measures of neuronal effects, and a similar temporal dissociation between subjective toxicity and maximum TMS change. The time course of neurophysiological effects, as measured by TMS, may help to explain the sustained clinical efficacy of LEV despite a short peripheral half-life.

Effect of pressure support vs unassisted breathing through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical ventilation: a randomized trial.

PubMed

Jubran, Amal; Grant, Brydon J B; Duffner, Lisa A; Collins, Eileen G; Lanuza, Dorothy M; Hoffman, Leslie A; Tobin, Martin J

2013-02-20

Patients requiring prolonged mechanical ventilation (>21 days) are commonly weaned at long-term acute care hospitals (LTACHs). The most effective method of weaning such patients has not been investigated. To compare weaning duration with pressure support vs unassisted breathing through a tracheostomy collar in patients transferred to an LTACH for weaning from prolonged ventilation. Between 2000 and 2010, a randomized study was conducted in tracheotomized patients transferred to a single LTACH for weaning from prolonged ventilation. Of 500 patients who underwent a 5-day screening procedure, 316 did not tolerate the procedure and were randomly assigned to receive weaning with pressure support (n = 155) or a tracheostomy collar (n = 161). Survival at 6- and 12-month time points was also determined. Primary outcome was weaning duration. Secondary outcome was survival at 6 and 12 months after enrollment. Of 316 patients, 4 were withdrawn and not included in analysis. Of 152 patients in the pressure-support group, 68 (44.7%) were weaned; 22 (14.5%) died. Of 160 patients in the tracheostomy collar group, 85 (53.1%) were weaned; 16 (10.0%) died. Median weaning time was shorter with tracheostomy collar use (15 days; interquartile range [IQR], 8-25) than with pressure support (19 days; IQR, 12-31), P = .004. The hazard ratio (HR) for successful weaning rate was higher with tracheostomy collar use than with pressure support (HR, 1.43; 95% CI, 1.03-1.98; P = .033) after adjusting for baseline clinical covariates. Use of the tracheostomy collar achieved faster weaning than did pressure support among patients who did not tolerate the screening procedure between 12 and 120 hours (HR, 3.33; 95% CI, 1.44-7.70; P = .005), whereas weaning time was equivalent with the 2 methods in patients who did not tolerate the screening procedure within 0 to 12 hours. Mortality was equivalent in the pressure-support and tracheostomy collar groups at 6 months (55.92% vs 51.25%; 4.67% difference, 95% CI, -6.4% to 15.7%) and at 12 months (66.45% vs 60.00%; 6.45% difference, 95% CI, -4.2% to 17.1%). Among patients requiring prolonged mechanical ventilation and treated at a single long-term care facility, unassisted breathing through a tracheostomy, compared with pressure support, resulted in shorter median weaning time, although weaning mode had no effect on survival at 6 and 12 months. clinicaltrials.gov Identifier: NCT01541462.

Effect of body posture on involuntary swallow in healthy volunteers.

PubMed

Shiino, Yoshitaka; Sakai, Shogo; Takeishi, Ryosuke; Hayashi, Hirokazu; Watanabe, Masahiro; Tsujimura, Takanori; Magara, Jin; Ito, Kayoko; Tsukada, Tetsu; Inoue, Makoto

2016-03-01

Clinically, reclining posture has been reported to reduce risk of aspiration. However, during involuntary swallow in reclining posture, changes in orofacial and pharyngeal movement before and during pharyngeal swallow should be considered. Further, the mechanisms underlying the effect of body posture on involuntary swallow remain unclear. The aim of the present study was to determine the effect of body posture on activity patterns of the suprahyoid muscles and on patterns of bolus transport during a natural involuntary swallow. Thirteen healthy male adults participated in a water infusion test and a chewing test. In the water infusion test, thickened water was delivered into the pharynx at a very slow rate until the first involuntary swallow was evoked. In the chewing test, subjects were asked to eat 10 g of gruel rice. In both tests, the recording was performed at four body postures between upright and supine positions. Results showed that reclining changed the location of the bolus head at the start of swallow and prolonged onset latency of the swallowing initiation. Muscle burst duration and whiteout time measured by videoendoscopy significantly increased with body reclining and prolongation of the falling time. In the chewing test, reclining changed the location of the bolus head at the start of swallow, and the frequency of bolus residue after the first swallow increased. Duration and area of EMG burst and whiteout time significantly increased with body reclining. These data suggest that body reclining may result in prolongation of pharyngeal swallow during involuntary swallow. Copyright © 2015 Elsevier Inc. All rights reserved.

T42. WHEN SHOULD EARLY INTERVENTION START, AND FOR HOW LONG SHOULD IT LAST?

PubMed Central

Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete

2018-01-01

Abstract Background Early intervention in psychosis facilities have often failed to integrate the two main elements of early intervention. While some facilities have focused on early, and have had Duration of Untreated Psychosis (DUP) as their main target, others have focused on the intervention and the treatment provided when patients were diagnosed. As both DUP reduction and specialized early intervention (SEI) has proved to have an effect on the treatment of patients with first-episode psychosis one could hope of a synergetic effect if the two strategies were integrated. In this study, we use data from a randomized clinical trial testing the effect of prolonged early intervention (5 years) compared to standard specialized early intervention (2 years). Overall the study found that both treatment groups remained stable or improved in psychopathology, functioning and cognition and that there was no further beneficial effect of the prolonged the treatment. Participants had a long DUP (median 52 weeks). For this specific sub-study we hypothesized that patients who were treated early in their course of illness would have a beneficial effect of the prolonged treatment compared to those who only received 2 years of specialized treatment. Methods 296 participants with a psychotic diagnosis within the schizophrenia spectrum (ICD 10 – F2x, excluding F21) were included. DUP start was assessed from first psychotic symptom equivalent to 3 or above on a global SAPS item. DUP stop was when patients started antipsychotic treatment or specialized early intervention treatment. To assess if there were a delay within the mental health referral system we used the national register to identify when participants first were diagnosed with a schizophrenia spectrum diagnosis and calculated the time until they started SEI treatment. Finally, we added the DUP and the treatment delay together to assess the time from first psychotic symptom until the start of adequate treatment (both antipsychotic medication and specialized early intervention treatment), called total treatment delay. We analyzed if there were a treatment effect for participants with DUP shorter than 3 months (n=79) and if there were an effect for participants with a total treatment delay shorter than 6 months (n=54). We used multiple imputations to correct for missing data at the follow-up. The data were analyzed using binary logistic regression for the dichotomous variables and linear regression for the continuous variables. Results At the five year follow-up, the participants who had a short DUP and had received 5 years of SEI treatment had lower psychopathological scores and higher level of functioning and cognition than those who only received 2 years of SEI treatment. The difference was not significant. For the patients who had a short total treatment delay there was a clear trend favoring the prolonged treatment and for negative symptoms there was a near significant effect of the prolonged treatment (estimated mean difference -0.61, 95% CI -1.2;0.006, p=0.05). Discussion Our findings are results of a sub-group analysis and should be interpreted with caution. Even if the results from the main trail did not find a significant effect of prolonged SEI treatment this sub-group analysis indicates that some of the explanation could be the delay prior to the start of treatment and that there could be a beneficial effect of the prolonged treatment if it actually were provided within the early years of illness and not just in the early years after diagnosis.

A test procedure for evaluating surgical hand disinfection.

PubMed

Babb, J R; Davies, J G; Ayliffe, G A

1991-06-01

A technique for assessing the immediate and prolonged efficacy of surgical scrubs and alcoholic hand rubs is described. A mean baseline count is obtained from all volunteers and logarithmic reductions in resident skin flora immediately after one or more applications, and after wearing gloves for 3 h, are measured. Loose-fitting surgical gloves are used for sampling resident flora. Preparations were applied using a standard technique for 2 min, apart from one test with 70% isopropanol (IPA) in which the application time was 30 s. Two studies are described, one of which compared four chlorhexidine scrubs, and the second 70% IPA, 7.5% povidone-iodine scrub, 2% triclosan cleanser and unmedicated bar soap. In spite of their constituent similarity, the four chlorhexidine scrubs varied considerably in efficacy and user acceptability. A 2 min application of 70% IPA was the most effective treatment, and gave log10 reductions of 1.65 for immediate and 1.58 for prolonged effect. This was marginally more effective than a 30 s application, but the difference was not significant. 'Hibiscrub' was the most effective aqueous formulation and gave reductions of 1.01 for immediate effect and 1.16 for prolonged effect. The test described could be used by reference centres and manufacturers to assess the efficacy of new and existing surgical hand disinfection formulations.

Cetuximab Plus Oxaliplatin May Not Be Effective Primary Treatment for Metastatic Colorectal Cancer

Cancer.gov

In a randomized phase III trial, the addition of the targeted therapy cetuximab to oxaliplatin and fluoropyrimidine chemotherapy did not prolong survival or time to disease progression of patients with advanced colorectal cancer.

Effect of prolonged bedrest and plus Gz acceleration on peripheral visual response time

NASA Technical Reports Server (NTRS)

Haines, R. F.

1973-01-01

Peripheral visual response time changes during +G sub z acceleration following fourteen days of bedrest are considered as well as what effect prolonged bedrest has upon this response. Eighteen test lights, placed 10 deg are apart along the horizontal meridian of the subject's field of view, were presented in a random sequence. The subject was instructed to press a button as soon as a light appeared. Response time testing occurred periodically during bedrest and continuously during centrifugation testing. The results indicate that: (1) mean response time is significantly longer to stimuli imaged in the far periphery than to stimuli imaged closer to the line of sight; (2) mean response time at each stimulus position tends to be longer at plateau g than during the preacceleration baseline period; (3) mean response time tends to lengthen as the g level is increased; (4) peripheral visual response time during +G sub x acceleration at 2, 3.2, and 3.8 g was not a reliable advanced indicator that blackout was going to occur; and (5) the subject's field of view collapsed rapidly just before blackout. Bedrest data showed that the distribution of response times to stimuli imaged across the subject's horizontal retinal meridian remained remarkably constant from day to day during both the bedrest and recovery periods.

Effect of growth time on Ti-doped ZnO nanorods prepared by low-temperature chemical bath deposition

NASA Astrophysics Data System (ADS)

Bidier, Shaker A.; Hashim, M. R.; Al-Diabat, Ahmad M.; Bououdina, M.

2017-04-01

Ti-doped ZnO nanorod arrays were grown onto Si substrate using chemical bath deposition (CBD) method at 93 °C. To investigate the effect of time deposition on the morphological, and structural properties, four Ti-doped ZnO samples were prepared at various deposition periods of time (2, 3.5, 5, and 6.5 h). FESEM images displayed high-quality and uniform nanorods with a mean length strongly dependent upon deposition time; i.e. it increases for prolonged growth time. Additionally, EFTEM images reveal a strong erosion on the lateral side for the sample prepared for 6.5 h as compared to 5 h. This might be attributed to the dissolution reaction of ZnO with for prolonged growth time. XRD analysis confirms the formation of a hexagonal wurtzite-type structure for all samples with a preferred growth orientation along the c-axis direction. The (100) peak intensity was enhanced and then quenched, which might be the result of an erosion on the lateral side of nanorods as seen in EFTEM. This study confirms the important role of growth time on the morphological features of Ti-doped ZnO nanorods prepared using CBD. Increase the growth time causes an erosion in lateral side -(100) direction XRD- and enhances the axial direction -(002), XRD.

The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders.

PubMed

Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete

2017-09-26

The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants were dichotomized based on DUP, treatment delay, and time from first symptom until start of SEI treatment. The groups were analyzed with regard to treatment response on psychopathology, level of functioning, and cognitive functioning. The participants with a short DUP had a tendency to respond better to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment for participants with a short total treatment delay could mean that prolonged SEI treatment is more beneficial than treatment as usual (TAU) so long as it is provided in the early years of illness and not just in the early years after diagnosis. THE EARLIER THE BETTER: The duration of untreated psychosis influences the long-term outcomes of treatment. Nikolai Albert, at the Copenhagen Mental Health Centre, and a team of Danish researchers have investigated the effects of a specialized early intervention program (OPUS) in 400 patients diagnosed with schizophrenia spectrum disorders and compared the effects of OPUS after two and five years. Their findings suggest that five years of specialized early intervention was most beneficial when the total duration from symptom start to treatment was shorter than 6 months. The treatment was particularly effective at improving patients' disorganized behavior and negative symptoms such as blunted emotions and lack of motivation. These findings support previous studies suggesting that patients are more responsive to treatment in the early years of illness and highlight the importance of avoiding delays within the mental health service provision.

Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia

PubMed Central

Lon, Chanthap; Spring, Michele; Sok, Sommethy; Ta-aksorn, Winita; Kodchakorn, Chanikarn; Pann, Sut-Thang; Chann, Soklyda; Ittiverakul, Mali; Sriwichai, Sabaithip; Buathong, Nillawan; Kuntawunginn, Worachet; So, Mary; Youdaline, Theng; Milner, Erin; Wojnarski, Mariusz; Lanteri, Charlotte; Manning, Jessica; Prom, Satharath; Haigney, Mark; Cantilena, Louis; Saunders, David

2017-01-01

ABSTRACT Despite the rising rates of resistance to dihydroartemisinin-piperaquine (DP), DP remains a first-line therapy for uncomplicated malaria in many parts of Cambodia. While DP is generally well tolerated as a 3-day DP (3DP) regimen, compressed 2-day DP (2DP) regimens were associated with treatment-limiting cardiac repolarization effects in a recent clinical trial. To better estimate the risks of piperaquine on QT interval prolongation, we pooled data from three randomized clinical trials conducted between 2010 and 2014 in northern Cambodia. A population pharmacokinetic model was developed to compare exposure-response relationships between the 2DP and 3DP regimens while accounting for differences in regimen and sample collection times between studies. A 2-compartment model with first-order absorption and elimination without covariates best fit the data. The linear slope-intercept model predicted a 0.05-ms QT prolongation per ng/ml of piperaquine (5 ms per 100 ng/ml) in this largely male population. Though the plasma half-life was similar in both regimens, peak and total piperaquine exposures were higher in those treated with the 2DP regimen. Furthermore, the correlation between the plasma piperaquine concentration and the QT interval prolongation was stronger in the population receiving the 2DP regimen. Neither the time since the previous meal nor the baseline serum magnesium or potassium levels had additive effects on QT interval prolongation. As electrocardiographic monitoring is often nonexistent in areas where malaria is endemic, 2DP regimens should be avoided and the 3DP regimen should be carefully considered in settings where viable alternative therapies exist. When DP is employed, the risk of cardiotoxicity can be mitigated by combining a 3-day regimen, enforcing a 3-h fast before and after administration, and avoiding the concomitant use of QT interval-prolonging medications. (This study used data from three clinical trials that are registered at ClinicalTrials.gov under identifiers NCT01280162, NCT01624337, and NCT01849640.) PMID:28193647

The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system.

PubMed

Hosgood, Sarah A; Shah, K; Patel, M; Nicholson, M L

2015-06-30

Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.

The Effect of Frequency Altered Feedback on Stuttering Duration and Type

ERIC Educational Resources Information Center

Stuart, Andrew; Frazier, Carmen L.; Kalinowski, Joseph; Vos, Paul W.

2008-01-01

Purpose: The effect of frequency altered feedback (FAF) on stuttering type (i.e., prolongation, repetition, or silent block) and stuttering duration (i.e., average duration of stuttering event and total stuttering time) was examined. Method: Retrospective analyses of previously collected data from 12 adult persons who stutter who participated in…

Effects of Nantucket pine tip moth insecticide spray schedules on loblolly pine seedlings

Treesearch

Christopher J. Fettig; Kenneth W. McCravy; C. Wayne Berisford

2000-01-01

Frequent and prolonged insecticide applications to control the Nantucket pine tip moth, Rhyacionia frustrana (Comstock) (Lepidoptera:Torticidae) (NPTM), although effective, may be impractical and uneconomica1, for commercial timber production. Timed insecticide sprays of permethrin (Polmce 3.2® EC) were applied to all possible combinations of spray...

Speech Perception in Complex Acoustic Environments: Developmental Effects

ERIC Educational Resources Information Center

Leibold, Lori J.

2017-01-01

Purpose: The ability to hear and understand speech in complex acoustic environments follows a prolonged time course of development. The purpose of this article is to provide a general overview of the literature describing age effects in susceptibility to auditory masking in the context of speech recognition, including a summary of findings related…

Efficiency of colorectal cancer care among veterans: analysis of treatment wait times at Veterans Affairs Medical Centers.

PubMed

Merkow, Ryan P; Bilimoria, Karl Y; Sherman, Karen L; McCarter, Martin D; Gordon, Howard S; Bentrem, David J

2013-07-01

Timeliness of cancer treatment is an important aspect of health care quality. Veterans Affairs Medical Centers (VAMCs) are expected to treat a growing number of patients with cancer. Our objectives were to examine treatment times from diagnosis to first-course therapy for patients with colon and rectal cancers and assess factors associated with prolonged wait times. From the VA Central Cancer Registry, patients who underwent colon or rectal resection for cancer from 1998 to 2008 were identified. Time from diagnosis to definitive cancer-directed therapy was measured, and multivariable regression methods were used to determine predictors of prolonged wait times for colon (≥ 45 days) and rectal (≥ 60 days) cancers. From 124 VAMCs, 14,097 patients underwent colectomy, and 3,390 underwent rectal resection for cancer. For colon cancer, the median time to treatment increased by 68% over time (P < .001). From 2007 to 2008, the median time to colectomy was 32 days. Predictors of prolonged wait times included age ≥ 55 years (v < 55 years), time period (2007 to 2008 v 1998 to 2000), black race (v white), marriage status (married v unmarried), high-volume center status (v low volume), and treatment at a different hospital (v same hospital as initial diagnosis; all P < .05). For rectal cancer, the overall median time to first-course treatment increased by 74% (P < .001). From 2007 to 2008, the median time to proctectomy was 47 days. Similar predictors of prolonged wait times were identified for rectal cancer. Time to first treatment has increased for patients with colon and rectal cancers at VAMCs. Patient, tumor, and hospital factors are associated with prolonged time to treatment.

Prolonged Heavy Vehicle Driving Performance: Effects of Unpredictable Shift Onset and Duration and Convoy versus Independent Driving Conditions

DTIC Science & Technology

1983-09-01

increase time headway. An impli- cation of this interpretation for driving safety is that where fatigued driv- ers are unable to compensate in this way...of driving safety these results provide an indi- cation of circumstances in which time headway is particularly short. Not surprisingly this measure is

Prolonged bradycardia, asystole and outcome of high spinal cord injury patients: Risk factors and management

PubMed Central

Shaikh, Nissar; Rhaman, M. A.; Raza, Ali; Shabana, Adel; Malstrom, Mahommad Faisal; Al-Sulaiti, Ghanem

2016-01-01

Background: High spinal cord injury (HSCI) is one of the devastating traumatic injuries. 80% of these patients are young male, and 93% will have major neurological disabilities. There is a paucity of literature about prolonged bradycardia in HSCI patients. The aim of this study was to know the prevalence, risk factors, precipitating factors for prolonged bradycardia in the HSCI patients. Materials and Methods: All patients who were admitted to the Intensive Care Unit (ICU) of a tertiary hospital, with spinal cord injury above level of dorsal (D4) were enrolled in this study prospectively. Patient's demographic data, mechanism, level and type of spinal injury, associated injuries, injury severity score (ISS), spinal shock, vasopressors used, time of occurrence of bradycardia, treatment for bradycardia, precipitating as well as risk factors and outcome were recorded. Results: During the study period, a total of 138 patients were admitted to the ICU with HSCI. Majority of patients were male. The most frequently associated injury in these patients was skeletal fractures (38.4%). Most common complication was pneumonia 56 (41%). Forty-five (33%) of the total patients had prolonged bradycardia; 87% of these patients had pneumonia when bradycardia occurred. 53.4% had cardiac asystole. 29 (21%) patients had bradycardia at the time of endotracheal suctioning, whereas 27 (20%) patients developed bradycardia at the time of positioning. Majority of the patients were managed conservatively. Those HSCI patients who developed prolonged bradycardia, their ISS score was statistically higher, ICU and hospital stay was significantly higher compared with those HSCI patient who did not have prolonged bradycardia. Multivariate analysis revealed that hypotension on admission; pneumonia, and tracheostomy were risk factors for the development of prolonged bradycardia in HSCI patients. Conclusion: Prolonged bradycardia was associated with significantly higher incidence of asystole. Endotracheal suctioning and positioning of HSCI patients were significant provocative factors for prolonged bradycardia; hypotension on admission, pneumonia and tracheostomy were the risk factors for the development of prolonged bradycardia in these patients. PMID:27695550

Intrathecal dexmedetomidine as adjuvant for spinal anaesthesia for perianal ambulatory surgeries: A randomised double-blind controlled study.

PubMed

Nethra, S S; Sathesha, M; Dixit, Aanchal; Dongare, Pradeep A; Harsoor, S S; Devikarani, D

2015-03-01

The newer trend in regional anaesthesia for ambulatory anorectal surgeries advocate use of lower dose of local anaesthetic, providing segmental block with adjuvants such as opioids and α2 agonists to prolong analgesia. The current study investigated effects of addition of 5 μg of dexmedetomidine to 6 mg of hyperbaric bupivacaine on duration of analgesia, sensory and motor block characteristics for perianal ambulatory surgeries. This study is a prospective randomised controlled double blind study. Forty adult patients between 18 and 55 years of age were divided into 2 groups. Group D received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml) with injection dexmedetomidine 5 μg in 0.5 ml of normal saline and Group N received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml) with 0.5 ml of normal saline. The parameters assessed were time to regression of sensory blockade, motor blockade, ambulation, time to void, first administration of analgesic. Statistical analysis was done using appropriate tests. Time for regression of sensory level and time for first administration of analgesic were prolonged in Group D (430.05 ± 89.13 min, 459.8 ± 100.9 min, respectively) in comparison to Group N (301.10 ± 94.86 min, 321.85 ± 95.08 min, respectively). However, the duration of motor blockade, time to ambulation, and time to void were also significantly prolonged in Group D (323.05 ± 54.58 min, 329.55 ± 54.06 min, 422.30 ± 87.59 min) than in Group N (220.10 ± 63.61 min, 221.60 ± 63.84 min, 328.45 ± 113.38 min). Intrathecal dexmedetomidine 5 μg added to intrathecal bupivacaine 6 mg as adjuvant may not be suitable for ambulatory perianal surgeries due to prolongation of motor blockade.

Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.

PubMed

Lim, Woo Hyeon; Park, Chang Min; Yoon, Soon Ho; Lim, Hyun-Ju; Hwang, Eui Jin; Lee, Jong Hyuk; Goo, Jin Mo

2018-03-01

To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.

The effect of the apneic period on the respiratory physiology of patients undergoing intubation in the ED.

PubMed

West, Jason R; Scoccimarro, Anthony; Kramer, Cody; Caputo, Nicholas D

2017-09-01

We sought to examine the physiological impact the apneic period has on the respiratory physiology of patients undergoing intubation in the emergency department and whether DAO, the delivery of 15L oxygen by nasal cannula during apnea, can affect the development of respiratory acidosis. This was a prospective observational cohort study conducted at an urban academic level 1 trauma center. A convenience sample of 100 patients was taken. Timed data collection forms were completed during the periintubation period. We report the mean ABG and end-tidal CO2 (EtCO2) values between those with normal and prolonged apnea times (>60s) and between those who received DAO and those who did not. 100 patients met our inclusion criteria. There were no significant differences in the pre-RSI ABG values between those who received DAO and those who did not and between those with apnea times less than or >60s. Only in the group of patients with apnea times >60s did significant changes in respiratory physiology occur. DAO did not alter the trend in respiratory acidosis during the periintubation period. EtCO2 increased as apnea times were prolonged, and DAO altered this trend. Post-RSI EtCO2 increased as apnea times were prolonged. DAO may alter this trend. Statistically significant changes in pH and PaCO2 (mean differences of 0.15 and 12.5, respectively) occurred in the group of patients who had mean apnea times of >60s but not in those with apnea times <60s. Copyright © 2017 Elsevier Inc. All rights reserved.

Short and prolonged exposure to hyperglycaemia in human fibroblasts and endothelial cells: metabolic and osmotic effects.

PubMed

Moruzzi, Noah; Del Sole, Marianna; Fato, Romana; Gerdes, Jantje M; Berggren, Per-Olof; Bergamini, Christian; Brismar, Kerstin

2014-08-01

High blood glucose levels are the main feature of diabetes. However, the underlying mechanism linking high glucose concentration to diabetic complications is still not fully elucidated, particularly with regard to human physiology. Excess of glucose is likely to trigger a metabolic response depending on the cell features, activating deleterious pathways involved in the complications of diabetes. In this study, we aim to elucidate how acute and prolonged hyperglycaemia alters the biology and metabolism in human fibroblasts and endothelial cells. We found that hyperglycaemia triggers a metabolic switch from oxidative phosphorylation to glycolysis that is maintained over prolonged time. Moreover, osmotic pressure is a major factor in the early metabolic response, decreasing both mitochondrial transmembrane potential and cellular proliferation. After prolonged exposure to hyperglycaemia we observed decreased mitochondrial steady-state and uncoupled respiration, together with a reduced ATP/ADP ratio. At the same time, we could not detect major changes in mitochondrial transmembrane potential and reactive oxygen species. We suggest that the physiological and metabolic alterations observed in healthy human primary fibroblasts and endothelial cells are an adaptive response to hyperglycaemia. The severity of metabolic and bioenergetics impairment associated with diabetic complications may occur after longer glucose exposure or due to interactions with cell types more sensitive to hyperglycaemia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pre-exercise glycerol hydration improves cycling endurance time

NASA Technical Reports Server (NTRS)

Montner, P.; Stark, D. M.; Riedesel, M. L.; Murata, G.; Robergs, R.; Timms, M.; Chick, T. W.

1996-01-01

The effects of glycerol ingestion (GEH) on hydration and subsequent cycle ergometer submaximal load exercise were examined in well conditioned subjects. We hypothesized that GEH would reduce physiologic strain and increase endurance. The purpose of Study I (n = 11) was to determine if pre-exercise GEH (1.2 gm/kg glycerol in 26 ml/kg solution) compared to pre-exercise placebo hydration (PH) (26 ml/kg of aspartame flavored water) lowered heart rate (HR), lowered rectal temperature (Tc), and prolonged endurance time (ET) during submaximal load cycle ergometry. The purpose of Study II (n = 7) was to determine if the same pre-exercise regimen followed by carbohydrate oral replacement solution (ORS) during exercise also lowered HR, Tc, and prolonged ET. Both studies were double-blind, randomized, crossover trials, performed at an ambient temperature of 23.5-24.5 degrees C, and humidity of 25-27%. Mean HR was lower by 2.8 +/- 0.4 beats/min (p = 0.05) after GEH in Study I and by 4.4 +/- 1.1 beats/min (p = 0.01) in Study II. Endurance time was prolonged after GEH in Study I (93.8 +/- 14 min vs. 77.4 +/- 9 min, p = 0.049) and in Study II (123.4 +/- 17 min vs. 99.0 +/- 11 min, p = 0.03). Rectal temperature did not differ between hydration regimens in both Study I and Study II. Thus, pre-exercise glycerol-enhanced hyperhydration lowers HR and prolongs ET even when combined with ORS during exercise. The regimens tested in this study could potentially be adapted for endurance activities.

A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite.

PubMed

Sonoda, Akinaga; Nitta, Norihisa; Tsuchiya, Keiko; Nitta-Seko, Ayumi; Ohta, Shinichi; Otani, Hideji; Murata, Kiyoshi

2016-12-01

Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd‑based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood‑pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM‑, CMEADM2‑, CMEADM+ (surface charges: ‑10.4, ‑41.0 and +9.6 mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO; ‑11.5 mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel = (SI post‑contrast ‑ SI pre‑contrast / SI pre‑contrast) x 100. Following injection with the CMEADMs, but not with USPIO, the in vivo pooling time was prolonged to >300 min. No significant differences were attributable to the electric charge among the CMEADM‑, CMEADM2‑ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently‑charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.

Physiologic effects of prolonged conducted electrical weapon discharge in ethanol-intoxicated adults.

PubMed

Moscati, Ronald; Ho, Jeffrey D; Dawes, Donald M; Miner, James R

2010-06-01

This study examines the physiologic effects of prolonged conducted electrical weapon (CEW) exposure on alcohol-intoxicated adult subjects. Adult volunteers were recruited at a TASER International training conference. All subjects ingested mixed drinks until clinical intoxication or until a minimum breath alcohol level of 0.08 mg/dL was achieved. Blood samples for venous pH, Pco(2), bicarbonate, and lactate were measured in all subjects at baseline, immediately after alcohol ingestion, immediately after exposure to a 15-second TASER X26 discharge (Taser International Inc, Scottsdale, AZ), and 24 hours post-alcohol ingestion. Laboratory values were compared at sampling times using repeated-measure analysis of variance. A focused analysis comparing time points within groups was then performed using paired t tests. Twenty-two subjects were enrolled into the study. There was a decrease in pH and bicarbonate and an increase in lactate after alcohol ingestion. There was a further increase in lactate and drop in pH after CEW exposure. No subject experienced a significant adverse event. All values had returned to baseline levels at 24 hours except lactate, which demonstrated a small but clinically insignificant increase. Prolonged continuous CEW exposure in the setting of acute alcohol intoxication has no clinically significant effect on subjects in terms of markers of metabolic acidosis. The acidosis seen is consistent with what occurs with ethanol intoxication or moderate exertion. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium.

PubMed

Knapp, J; Bokník, P; Linck, B; Läer, S; Müller, F U; Neumann, J; Vahlensieck, U; Schlüter, H; Zidek, W; Schmitz, W

1999-09-01

In human ventricular trabeculae carneae 100 microM AP4A (diadenosine tetraphosphate) increased force of contraction to 162.8+/-15.7% of predrug value (n=9). This positive inotropic effect was accompanied by a prolongation of time parameters: time to peak tension and time of relaxation were prolonged by 7.8+/-1.3% and 14.9+/-3.8%, respectively (P<0.05). In the same trabeculae, AP4A increased IP3 (inositol-1,4,5-trisphosphate) content from 9.0+/-1.3 pmol/mg to 22.9+/-5.4 pmol/mg protein (n=5-9). In conclusion, the positive inotropic effect of AP4A in the human myocardium is likely due to an increase of IP3 mediated probably via Gq-coupled P2Y-purinoceptors. Because of the prominent role of Gq in the development of cardiac disease, these findings may lay the ground to further investigate the possible role of AP4A and/or related ligands (e.g. AP2A and AP3A) in heart failure.

Immunomodulation by blockade of the TRANCE co-stimulatory pathway in murine allogeneic islet transplantation

PubMed Central

Wojtusciszyn, Anne; Andres, Axel; Morel, Philippe; Charvier, Solange; Armanet, Mathieu; Toso, Christian; Choi, Yongwon; Bosco, Domenico; Berney, Thierry

2010-01-01

We explore herein the effect of TRANCE costimulatory pathway blockade on islet survival after allograft transplantation. Expression of TRANCE on murine C57BL/6 (B6) CD4+ T-cells after allogeneic activation was analysed by FACS. The effect of a TRANCE receptor fusion protein (TR-Fc) and anti-CD154 antibody (MR1) on B6 spleen cell proliferation after allogeneic activation was assessed by MLR. Three groups of B6 mice were transplanted with allogeneic islets (DBA2): Control; short-term TR-Fc-treatment (days 0–4); and prolonged TR-Fc-treatment (days -1–13). Donor-specific transfusion (DST) was performed at the time of islet transplantation in one independent experiment. Transplantectomy samples were analyzed by immunohistochemistry. TRANCE expression was upregulated in stimulated CD4+ T-cells in vitro. In MLR experiments, TR-Fc and MR1 both reduced spleen cell proliferation, but less than the combination of both molecules. Short course TR-Fc treatment did not prolong islet graft survival as compared to controls (10.6±1.9 vs 10.7±1.5 days) in contrast to prolonged treatment (20.7±3.2 days; p<0.05). After DST, primary non-function (PNF) was observed in half of control mice, but never in TR-Fc-treated mice. Immunofluorescence staining for Mac-1 showed a clear decrease in macrophage recruitment in the treated groups. TRANCE targeting may be an effective strategy for the prolongation of allogeneic islet graft survival, thanks to its inhibitory effects on costimulatory signals and macrophage recruitment. PMID:19453995

Prolonged sedentary time and physical activity in workplace and non-work contexts: a cross-sectional study of office, customer service and call centre employees.

PubMed

Thorp, Alicia A; Healy, Genevieve N; Winkler, Elisabeth; Clark, Bronwyn K; Gardiner, Paul A; Owen, Neville; Dunstan, David W

2012-10-26

To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts. A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (<100 counts per minute; cpm), in prolonged sedentary bouts (≥20 minutes or ≥30 minutes), light-intensity activity (100-1951 cpm) and moderate-to-vigorous physical activity (MVPA; ≥1952 cpm). Using mixed models adjusted for confounders, these were compared for: work days versus non-work days; work hours versus non-work hours (work days only); and, across workplace settings. Working hours were mostly spent sedentary (77.0%, 95%CI: 76.3, 77.6), with approximately half of this time accumulated in prolonged bouts of 20 minutes or more. There were significant (p<0.05) differences in all outcomes between workdays and non-work days, and, on workdays, between work- versus non-work hours. Results consistently showed "work" was more sedentary and had less light-intensity activity, than "non-work". The period immediately after work appeared important for MVPA. There were significant (p<0.05) differences in all sedentary and activity outcomes occurring during work hours across the workplace settings. Call-centre workers were generally the most sedentary and least physically active at work; customer service workers were typically the least sedentary and the most active at work. The workplace is a key setting for prolonged sedentary time, especially for some occupational groups, and the potential health risk burden attached requires investigation. Future workplace regulations and health promotion initiatives for sedentary occupations to reduce prolonged sitting time should be considered.

Phasic heart rate responses and cardiac cycle time in auditory choice reaction time.

PubMed

van der Molen, M W; Somsen, R J; Orlebeke, J F

1983-01-01

This study investigated the cardiovascular-behavioral interaction under short and long stimulus interval conditions. In addition, the cardiovascular-behavioral interaction was studied as affected by cardiac cycle duration. Fourteen subjects performed a choice reaction time (RT) task employing a mixed speed-accuracy tradeoff design in which reactions were paced to coincide with a signal that occurs randomly at either 200 or 500 msec after the reaction stimulus. The preparatory interval between a warning stimulus and a lead-reaction stimulus complex was also varied (2 vs. 4.5 sec). Anticipatory deceleration occurred within the 4.5 sec interval but not in the 2 sec interval. The depth of anticipatory deceleration did not discriminate between fast and slow reactions; but an earlier shift from deceleration to acceleration was associated with fast reactions. The effect of stimulus timing relative to the R-wave of the electrocardiogram was also analysed. Meaningful stimuli tended to produce cardiac slowing as previously described in the literature. Early occurring stimuli prolong the cycle of their occurrence more than late occurring stimuli. The later prolong the subsequent cycle. Cardiac cycle time effects were absent for unattended stimuli. The results of anticipatory deceleration suggested that the depth of deceleration was regulated by time-uncertainty and speed-accuracy criterion.

The impacts of repeated cold exposure on insects.

PubMed

Marshall, Katie E; Sinclair, Brent J

2012-05-15

Insects experience repeated cold exposure (RCE) on multiple time scales in natural environments, yet the majority of studies of the effects of cold on insects involve only a single exposure. Three broad groups of experimental designs have been employed to examine the effects of RCE on insect physiology and fitness, defined by the control treatments: 'RCE vs cold', which compares RCE with constant cold conditions; 'RCE vs warm', which compares RCE with constant warm conditions; and 'RCE vs matched cold' which compares RCE with a prolonged period of cold matched by time to the RCE condition. RCE are generally beneficial to immediate survival, and increase cold hardiness relative to insects receiving a single prolonged cold exposure. However, the effects of RCE depend on the study design, and RCE vs warm studies cannot differentiate between the effects of cold exposure in general vs RCE in particular. Recent studies of gene transcription, immune function, feeding and reproductive output show that the responses of insects to RCE are distinct from the responses to single cold exposures. We suggest that future research should attempt to elucidate the mechanistic link between physiological responses and fitness parameters. We also recommend that future RCE experiments match the time spent at the stressful low temperature in all experimental groups, include age controls where appropriate, incorporate a pilot study to determine time and intensity of exposure, and measure sub-lethal impacts on fitness.

Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: a study of a two-week teaching practice.

PubMed

Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Sugaya, Nagisa; Nomura, Shinobu

2012-06-01

This study investigated variations in salivary levels of cortisol and dehydroepiandrosterone (DHEA) in a prolonged stressful situation (a two-week teaching practice). Thirty-three women for whom a two-week teaching practice at a kindergarten was scheduled were asked to collect saliva samples at awakening, 30 min after awakening, and bedtime at four time points: two weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. In addition, they completed questionnaires for assessing perceived stress and subjective moods on each day. A linear mixed model indicated that cortisol levels significantly increased during the first and second week of the practice compared with those before and after the practice period, and that DHEA levels significantly decreased after the practice period compared with those at the other time points. Further, cortisol awakening response after the practice period significantly reduced compared with that at the other time points. Scores of perceived stress and negative moods were also higher during the practice period. This study showed that prolonged stress affected cortisol and DHEA secretion during as well as after the stress period. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hyperbaric nitrogen prolongs breath-holding time in humans.

PubMed

Morooka, H; Wakasugi, Y; Shimamoto, H; Shibata, O; Sumikawa, K

2000-09-01

Either an increase in PaCO(2) or a decrease in PaO(2), can affect respiratory stimulation through respiratory centers, thus influencing breath-holding time (BHT). This study was designed to determine whether and how hyperbaric air could influence BHT in comparison with hyperbaric oxygen in humans. We studied 36 healthy volunteers in a multiplace hyperbaric chamber. BHT, pulse oximeter, and transcutaneous carbon dioxide tension were measured at 1 and 2.8 atmosphere absolute (ATA) in two groups. Group A (n = 20) breathed air. Group O (n = 16) breathed oxygen with a face mask (5 L/min). BHTs were 108 +/- 28 s at 1.0 ATA and 230 +/- 71 s at 2.8 ATA in Group A, and 137 +/- 48 s at 1.0 ATA and 180 +/- 52 s at 2.8 ATA in Group O. Transcutaneous carbon dioxide tension in Group A (59 +/- 2 mm Hg) was higher than that in Group O (54 +/- 2 mm Hg) at the end of maximal breath-holding at 2.8 ATA. The prolongation of BHT in hyperbaric air is significantly greater than that in hyperbaric oxygen. Breath-holding time is significantly prolonged in hyperbaric air than it is in hyperbaric oxygen. The mechanism involves the anesthetic effect of nitrogen suppressing the suffocating feeling during breath-holding.

Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex.

PubMed

Hysek, Cédric M; Liechti, Matthias E

2012-12-01

Pupillometry can be used to characterize autonomic drug effects. This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function. Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo-MDMA (125 mg), placebo-placebo, pretreatment-placebo, or pretreatment-MDMA using a crossover design. MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function. The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration-time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.

Prolonging the duration of single-shot intrathecal labour analgesia with morphine: A systematic review.

PubMed

Al-Kazwini, Hadeel; Sandven, Irene; Dahl, Vegard; Rosseland, Leiv Arne

2016-10-01

Single-shot spinal with bupivacaine plus fentanyl or sufentanil is commonly used as analgesia during labour, but the short duration limits the clinical feasibility. Different drugs have been added to prolong the analgesic duration. The additional effect of intra-thecal morphine has been studied during labour pain as well as after surgery. We assessed whether adding morphine to intra-thecal bupivacaine+fentanyl or sufentanil prolongs pain relief during labour. Meta-analysis of placebo-controlled randomized clinical trials of analgesia prolongation after single-shot intrathecal morphine ≤250μg during labour when given in combination with bupivacaine+fentanyl or sufentanil. After identifying 461 references, 24 eligible studies were evaluated after excluding duplicate publications, case reports, studies of analgesia after caesarean delivery, and epidural labour analgesia. Mean duration in minutes was the primary outcome measure and was included in the calculation of the standardized mean difference. Duration was defined as the time between a single shot spinal until patient request of rescue analgesia. All reported side effects were registered. Results of individual trials were combined using a random effect model. Cochrane tool was used to assess risk of bias. Five randomized placebo-controlled clinical trials (286 patients) were included in the meta-analysis. A dose of 50-250μg intrathecal morphine prolonged labour analgesia by a mean of 60.6min (range 3-155min). Adding morphine demonstrated a medium beneficial effect as we found a pooled effect of standardized mean difference=0.57 (95% CI: -0.10 to 1.24) with high heterogeneity (I 2 =88.1%). However, the beneficial effect was statistically non-significant (z=1.66, p=0.096). The lower-bias trials showed a small statistically non-significant beneficial effect with lower heterogeneity. In influential analysis, that excluded one study at a time from the meta-analysis, the effect size appears unstable and the results indicate no robustness of effect. Omitting the study with highest effects size reduces the pooled effect markedly and that study suffers from inadequate concealment of treatment allocation and blinding. Trial quality was generally low, and there were too few trials to explore sources of heterogeneity in meta-regression and stratified analyses. In general, performing meta-analyses on a small number of trials are possible and may be helpful if one is aware of the limitations. As few as one more placebo-controlled trial would increase the reliability greatly. Evidence from this systematic review suggests a possible beneficial prolonging effect of adding morphine to spinal analgesia with bupivacaine+fentanyl or +sufentanil during labour. The study quality was low and heterogeneity high. No severe side effects were reported. More adequately-powered randomized trials with low bias are needed to determine the benefits and harms of adding morphine to spinal local anaesthetic analgesia during labour. Epidural analgesia is documented as the most effective method for providing pain relief during labour, but from a global perspective most women in labour have no access to epidural analgesia. Adding morphine to single shot spinal injection of low dose bupivacaine, fentanyl or sufentanil may be efficacious but needs to be investigated. Copyright © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

What Prolongs a Butterfly's Life?: Trade-Offs between Dormancy, Fecundity and Body Size

PubMed Central

Haeler, Elena; Fiedler, Konrad; Grill, Andrea

2014-01-01

In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies’ life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h), thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13). Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels. PMID:25390334

Efficacy of an outpatient treatment for prolonged grief disorder: a randomized controlled clinical trial.

PubMed

Rosner, Rita; Pfoh, Gabriele; Kotoučová, Michaela; Hagl, Maria

2014-01-01

Abnormal forms of grief, currently referred to as complicated grief or prolonged grief disorder, have been discussed extensively in recent years. While the diagnostic criteria are still debated, there is no doubt that prolonged grief is disabling and may require treatment. To date, few interventions have demonstrated efficacy. We investigated whether outpatients suffering from prolonged grief disorder (PGD) benefit from a newly developed integrative cognitive behavioural therapy for prolonged grief (PG-CBT). A total of 51 patients were randomized into two groups, stratified by the type of death and their relationship to the deceased; 24 patients composed the treatment group and 27 patients composed the wait list control group (WG). Treatment consisted of 20-25 sessions. Main outcome was change in grief severity; secondary outcomes were reductions in general psychological distress and in comorbidity. Patients on average had 2.5 comorbid diagnoses in addition to PGD. Between group effect sizes were large for the improvement of grief symptoms in treatment completers (Cohen׳s d=1.61) and in the intent-to-treat analysis (d=1.32). Comorbid depressive symptoms also improved in PG-CBT compared to WG. The completion rate was 79% in PG-CBT and 89% in WG. The major limitations of this study were a small sample size and that PG-CBT took longer than the waiting time. PG-CBT was found to be effective with an acceptable dropout rate. Given the number of bereaved people who suffer from PGD, the results are of high clinical relevance. Copyright © 2014 Elsevier B.V. All rights reserved.

Incorporating peer support during in vivo exposure to reverse dropout from prolonged exposure therapy for posttraumatic stress disorder: Clinical outcomes.

PubMed

Hernandez-Tejada, Melba A; Hamski, Stephanie; Sánchez-Carracedo, David

2017-01-01

Objective Prolonged exposure is characterized by reported dropout rates ranging from 25% to 40%. This premature attrition is also observed in other evidence-based treatments for posttraumatic stress disorder. While home-based telehealth delivery of prolonged exposure resolves logistical barriers to care such as travel time and cost, dropout appears unaffected. A previous study on dropouts from prolonged exposure delivered via telehealth found that Veterans, particularly those receiving care via telehealth, reported problems with in vivo exposure and that having a peer to offer support during in vivo exposure assignments might have prevented their attrition from treatment. Methods The present pilot study treatment was designed in a manner consistent with the aforementioned Veteran suggestions, specifically to involve peers offering verbal support and encouragement during in vivo exposure homework. Such a treatment modification might be particularly useful for those receiving care via telehealth, given increased difficulties with exposure reported when this treatment delivery modality is used. It was hypothesized that dropouts would agree to reengage in treatment with a peer and would subsequently evince improvement in posttraumatic stress disorder and depression scores as a result of this treatment reengagement. Results Of 82 dropouts from prolonged exposure, 29 reentered treatment when offered peer support during exposure (12 in telehealth and 17 in person). Conclusion Treatment reentry was effective insofar as indices of both posttraumatic stress disorder and depression were significantly reduced in both telehealth and in person groups, indicating that using peers in this way may be an effective means by which to return Veterans to care, and ultimately reduce symptomatology.

Effect of styrene maleic acid WIN55,212-2 micelles on neuropathic pain in a rat model.

PubMed

Linsell, Oliver; Brownjohn, Philip W; Nehoff, Hayley; Greish, Khaled; Ashton, John C

2015-05-01

Cannabinoid receptor agonists are moderately effective at reducing neuropathic pain but are limited by psychoactivity. We developed a styrene maleic acid (SMA) based on the cannabinoid WIN 55,212-2 (WIN) and tested in a rat model of neuropathic pain and in the rotarod test. We hypothesized that miceller preparation can ensure prolonged plasma half-life being above the renal threshold of excretion. Furthermore, SMA-WIN could potentially reduce the central nervous system effects of encapsulated WIN by limiting its transport across the blood-brain barrier. Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period compared to control (base WIN). Attenuation of chronic constriction injury-induced mechanical allodynia occurred for up to 8 h at a dose of 11.5 mg/kg of SMA-WIN micelles. To evaluate central effects on motor function, the rotarod assessment was utilized. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN control for up to 1.5 h. Despite this, the SMA-WIN micelle formulation was able to produce prolonged analgesia over a time when there was decreased impairment in the rotarod test compared with base WIN.

Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials

PubMed Central

2011-01-01

Background The emergence of multi-drug resistant Gram-negatives (MDRGNs) coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion. Methods Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models. Results Fourteen randomized controlled trials (RCTs) were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37) or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06) compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws. Conclusions No clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed. PMID:21696619

Distinct effects of brief and prolonged adaptation on orientation tuning in primary visual cortex

PubMed Central

Patterson, Carlyn A.; Wissig, Stephanie C.; Kohn, Adam

2013-01-01

Recent stimulus history–adaptation–alters neuronal responses and perception. Previous electrophysiological and perceptual studies suggest that prolonged adaptation strengthens and makes more persistent the effects seen after briefer exposures. However, no systematic comparison has been made between the effects of adaptation lasting hundreds of milliseconds, which might arise during a single fixation, and the more prolonged adaptation typically used in imaging and perceptual studies. Here we determine how 0.4 s, 4 s, and 40 s of adaptation alters orientation tuning in primary visual cortex of anesthetized macaque monkeys, and how quickly responses recover after adapter offset. We measured responses to small (1.3 deg) and large (7.4 deg) gratings because previous work has shown that adaptation effects can depend on stimulus size. Adaptation with small gratings reduced responsivity and caused tuning to shift away from the adapter. These effects strengthened with more prolonged adaptation. For responses to large gratings, brief and prolonged adaptation produced indistinguishable effects on responsivity but caused opposite shifts in tuning preference. Recovery from adaptation was notably slower after prolonged adaptation, even when this did not induce stronger effects. We show that our results can be explained by an adaptation-induced weakening of surround suppression, the dynamics of this suppression, and differential effects of brief and prolonged adaptation across response epochs. Our findings show that effects do not simply scale with adaptation duration, and suggest that distinct strategies exist for adjusting to moment-to-moment fluctuations in input and to more persistent visual stimuli. PMID:23303933

The effect of heat acclimation on sweat microminerals: Artifact of surface contamination

USDA-ARS?s Scientific Manuscript database

Heat acclimation (HA) reportedly conveys conservation in sweat micromineral concentrations when sampled from arm sweat, but time course is unknown. The observation that comprehensive cleaning of the skin surface negates sweat micromineral reductions during prolonged sweating raises the question of w...

Effect of storage time on the viability of cryopreserved bovine spermatozoa

USDA-ARS?s Scientific Manuscript database

Long term cryopreserved semen viability can impact the National Animal Germplasm Program’s (NAGP) sampling strategy and ability to reconstitute livestock populations. Therefore, the purpose of this project was to determine if prolonged storage of cryopreserved sperm impacts cell viability. Cryoprese...

Bisphenol A exposure and cardiac electrical conduction in excised rat hearts.

PubMed

Posnack, Nikki Gillum; Jaimes, Rafael; Asfour, Huda; Swift, Luther M; Wengrowski, Anastasia M; Sarvazyan, Narine; Kay, Matthew W

2014-04-01

Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. The goal of our study was to measure the effect of BPA (0.1-100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1-100 μM BPA), prolonged action potential duration (1-100 μM BPA), and delayed atrioventricular conduction (10-100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA's effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations.

Effect of a 2-h hyperglycemic-hyperinsulinemic glucose clamp to promote glucose storage on endurance exercise performance.

PubMed

Maclaren, D P M; Mohebbi, H; Nirmalan, M; Keegan, M A; Best, C T; Perera, D; Harvie, M N; Campbell, I T

2011-09-01

Carbohydrate stores within muscle are considered essential as a fuel for prolonged endurance exercise, and regimes for enhancing such stores have proved successful in aiding performance. This study explored the effects of a hyperglycaemic-hyperinsulinemic clamp performed 18 h previously on subsequent prolonged endurance performance in cycling. Seven male subjects, accustomed to prolonged endurance cycling, performed 90 min of cycling at ~65% VO(2max) followed by a 16-km time trial 18 h after a 2-h hyperglycemic-hyperinsulinemic clamp (HCC). Hyperglycemia (10 mM) with insulin infused at 300 mU/m(2)/min over a 2-h period resulted in a total glucose uptake of 275 g (assessed by the area under the curve) of which glucose storage accounted for about 73% (i.e. 198 g). Patterns of substrate oxidation during 90-min exercise at 65% VO(2max) were not altered by HCC. Blood glucose and plasma insulin concentrations were higher during exercise after HCC compared with control (p < 0.05) while plasma NEFA was similar. Exercise performance was improved by 49 s and power output was 10-11% higher during the time trial (p < 0.05) after HCC. These data suggest that carbohydrate loading 18 h previously by means of a 2-h HCC improves cycling performance by 3.3% without any change in pattern of substrate oxidation.

Comparative sensitivity of commercially available aPTT reagents to mulga snake (Pseudechis australis) venom.

PubMed

Lincz, Lisa F; Scorgie, Fiona E; Johnston, Christopher I; O'Leary, Margaret; Prasad, Ritam; Seldon, Michael; Favaloro, Emmanuel; Isbister, Geoffrey K

2014-08-01

This study aimed to determine the relative sensitivity of activated partial thromboplastin time (aPTT) reagents to the anticoagulant effects of phospholipases in mulga snake (Pseudechis australis) venom.Twenty-one haematology laboratories participating in the Royal College of Pathologists of Australasia Quality Assurance Programs were sent human plasma samples spiked with mulga venom (n=25 total results). Results for 17 patients with mulga snake envenoming were available through the Australian Snakebite Project.Only 12 of 25 venom spiked samples returned an abnormally prolonged aPTT. Tests performed with Dade Actin FS (n=7) did not identify any of the spiked samples as abnormal. Although clotting times were significantly prolonged using the lupus anticoagulant sensitive Actin FSL (n=5, p=0.043), only one was reported as abnormal. Only laboratories using TriniCLOT aPTT S (n=6), HemosIL APTT SP (n=2) and Stago PTT-A (n=1) consistently recorded the spiked sample as being above the upper normal reference interval. Abnormally prolonged aPTTs were recorded for four of eight patients whose tests were performed with Actin FSL, five of eight patients with TriniCLOT aPTT HS, and three of three patients using TriniCLOT aPTT S.We conclude that some reagents used for routine aPTT testing are relatively insensitive to the anticoagulant effects of mulga snake venom. Tests performed with these reagents should be interpreted with caution.

The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): Interference of C-reactive protein.

PubMed

Liu, Jie; Li, Fanfan; Shu, Kuangyi; Chen, Tao; Wang, Xiaoou; Xie, Yaoqi; Li, Shanshan; Zhang, Zhaohua; Jin, Susu; Jiang, Minghua

2018-05-13

To investigate the effect of C-reactive protein on the activated partial thromboplastin time (APTT) (different activators) in different detecting systems. The C-reactive protein and coagulation test of 112 patients with the infectious disease were determined by automation protein analyzer IMMAG 800 and automation coagulation analyzer STA-R Evolution, respectively. The pooled plasma APTT with different concentrations of C-reactive protein was measured by different detecting system: STA-R Evolution (activator: silica, kaolin), Sysmex CS-2000i (activator: ellagic acid), and ACL TOP 700 (activator: colloidal silica). In addition, the self-made platelet lysate (phospholipid) was added to correct the APTT prolonged by C-reactive protein (150 mg/L) on STA-R Evolution (activator: silica) system. The good correlation between C-reactive protein and APTT was found on the STA-R Evolution (activator: silica) system. The APTT on the STA-R Evolution (activator: silica) system was prolonged by 24.6 second, along with increasing C-reactive protein concentration. And the APTT of plasma containing 150 mg/L C-reactive protein was shortened by 3.4-6.9 second when the plasma was mixed with self-made platelet lysate. However, the APTT was prolonged unobviously on other detecting systems including STA-R Evolution (activator: kaolin), Sysmex CS-2000i, and ACL TOP 700. C-reactive protein interferes with the detection of APTT, especially in STA-R Evolution (activator: silica) system. The increasing in C-reactive protein results in a false prolongation of the APTT (activator: silica), and it is most likely that C-reactive protein interferes the coagulable factor binding of phospholipid. © 2018 Wiley Periodicals, Inc.

Length of Recovery From Sports-Related Concussions in Pediatric Patients Treated at Concussion Clinics.

PubMed

Thomas, Donald J; Coxe, Kathryn; Li, Hongmei; Pommering, Thomas L; Young, Julie A; Smith, Gary A; Yang, Jingzhen

2018-01-01

We quantified the length of recovery time by week in a cohort of pediatric sports-related concussion patients treated at concussion clinics, and examined patient and injury characteristics associated with prolonged recovery. A retrospective, cohort design. Seven concussion clinics at a Midwest children's hospital. Patients aged 10 to 17 years with a diagnosed sports-related concussion presenting to the clinic within 30 days of injury. Length of recovery by week. Unadjusted and adjusted multinomial logistic regression analyses were used to model the effect of patient and injury characteristics on length of recovery by week. Median length of recovery was 17 days. Only 16.3% (299/1840) of patients recovered within one week, whereas 26.4% took longer than four weeks to recover. By 2 months postinjury, 6.7% of patients were still experiencing symptoms. Higher symptom scores at injury and initial visit were significantly associated with prolonged symptoms by week. Patients who presented to the clinic more than 2 weeks postinjury or who had 2 or more previous concussions showed increased risk for prolonged recovery. Females were at greater risk for prolonged recovery than males (odds ratio = 2.08, 95% confidence interval = 1.49-2.89). Age was not significantly associated with recovery length. High symptom scores at injury and initial visit, time to initial clinical presentation, presence of 2 or more previous concussions, and female sex are associated with prolonged concussion recovery. Further research should aim to establish objective measures of recovery, accounting for treatment received during the recovery. The median length of recovery is 17 days among pediatric sports-related concussion patients treated at concussion clinics. Only 16.3% of patients recovered within one week, whereas 26.4% took longer than 4 weeks to recover.

Effect Of Pressure Support Versus Unassisted Breathing Through A Tracheostomy Collar On Weaning Duration In Patients Requiring Prolonged Mechanical Ventilation: A Randomized Trial

PubMed Central

Jubran, Amal; Grant, Brydon J.B.; Duffner, Lisa A.; Collins, Eileen G.; Lanuza, Dorothy M.; Hoffman, Leslie A.; Tobin, Martin J.

2013-01-01

Context Patients requiring prolonged mechanical ventilation (more than 21 days) are commonly weaned at long-term acute care hospitals (LTACHs). The most effective method of weaning such patients has not been investigated. Objective To compare weaning duration with pressure support versus unassisted breathing through a tracheostomy (trach collar) in patients transferred to a LTACH for weaning from prolonged ventilation. Design, Settings, and Participants Between 2000 and 2010, a randomized study was conducted in tracheotomized patients transferred to a single LTACH for weaning from prolonged ventilation. Of 500 patients who underwent a five-day screening procedure, 316 failed and were randomly assigned to wean with pressure support (n=155) or a trach collar (n=161). Six- and twelve-month survival was also determined. Main outcome measure Primary outcome was weaning duration. Secondary outcome was survival at six and twelve months after enrollment. Results Of 316 patients, four were withdrawn and not included in analysis. Of 152 patients in the pressure-support arm, 68 (44.7%) were weaned; 22 (14.5%) died. Of 160 patients in the trach-collar arm, 85 (53.1%) were weaned; 16 (10.0%) died. Median weaning time was shorter with trach collar than with pressure support: 15 [interquartile range, 8–25] versus 19 [12–31] days, p=0.004. The hazard ratio (HR) for successful weaning rate was higher with trach collar than with pressure support (HR, 1.43; 95% confidence interval [CI], 1.03–1.98, p<0.03) after adjusting for baseline clinical covariates. Trach collar achieved faster weaning than did pressure support among subjects who failed the screening procedure at 12–120 hours (HR, 3.33; 95% CI, 1.44–7.70, p<0.01), whereas weaning time was equivalent with the two methods in patients who failed the screening procedure within 0–12 hours. Mortality was equivalent in the pressure-support and trach-collar arms at six months (55.9% versus 51.3%; 4.7 difference, 95% CI −6.4 to 15.7%) and twelve months (66.4% versus 60.0%; 6.5 difference, 95% CI −4.2 to 17.1 %). Conclusion Among patients requiring prolonged mechanical ventilation and treated at a single long-term care facility, unassisted breathing through a tracheostomy, compared with pressure support, resulted in shorter median weaning time, although weaning mode had no effect on survival at 6 and 12 months. PMID:23340588

Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

PubMed

Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

2016-01-01

Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

Response of Pink Lady® apples to post-harvest application of 1-methylcyclopropene as a function of applied dose, maturity at harvest, storage time and controlled atmosphere storage.

PubMed

Cocci, Emiliano; Sacchetti, Giampiero; Rocculi, Pietro; Dalla Rosa, Marco

2014-10-01

1-Methylcyclopropene (1-MCP) is an inhibitor of ethylene reception used in post-harvest treatments to delay fruit ripening. Several factors affect the efficacy of 1-MCP treatments. The effect of a post-harvest treatment with 1-MCP on the quality of Pink Lady® apples as a function of 1-MCP dose, storage time and maturity at harvest was investigated. 1-MCP treatment was further tested in combination with controlled atmosphere (CA) storage. 1-MCP limited fruit respiration and softening during storage and was more effective on partially matured fruits and at prolonged storage times. The delaying of 1-MCP on the increase of ripening index was greater on matured fruits at prolonged storage times. The combination of 1-MCP and CA treatments positively affected quality indices of mature apples during 6 months of storage and 7 days of commercial life, with 1-MCP being more effective than CA. 1-MCP and CA showed positive combined effects on firmness and ripening index after 6 months of storage, and on firmness and CO₂ production after a further 7 days of commercial life. By knowing fruit maturity at harvest and expected storage time it is possible to choose the most suitable 1-MCP dose to meet the market requirements by applying a simple polynomial model. © 2014 Society of Chemical Industry.

Ibudilast, a phosphodiesterase inhibitor, in combination with low-dose aspirin potently inhibits guinea pig carotid artery thrombosis without extending bleeding time and causing gastric mucosal injury.

PubMed

Matsuzawa, S; Hoshina, K; Sueyoshi, S; Miyata, Y; Manita, S; Ooie, T; Yasue, T; Sasahara, T

2012-12-01

A combination of low-dose aspirin (ASA) and a phosphodiesterase inhibitor has been clinically tried for the secondary prevention of atherothrombotic diseases. The in vivo antithrombotic property of ibudilast (CAS 50847-11-5), a phosphodiesterase 4 (PDE4) inhibitor, was evaluated in a photochemically-induced guinea pig carotid artery thrombosis model in combination with low-dose ASA. The time required to decrease the carotid artery blood flow to the reading "zero" was defined as the time to occlusion (TTO) of the artery through thrombogenesis. Each independent use of ASA (300 mg/kg, p.o.) and ibudilast (3 and 10 mg/kg, p.o.) significantly prolonged the TTO, and ASA (300 mg/kg) significantly increased bleeding time (BT) and gastric mucosal injury. A selective PDE4 inhibitor rolipram (1 and 5 mg/kg, p.o.) tended to prolong the TTO without extending BT. ASA (100 mg/kg) plus ibudilast (3 mg/kg) and ASA (100 mg/kg) plus rolipram (5 mg/kg) markedly prolonged the TTO compared with each agent alone. Interestingly, ASA (100 mg/kg) plus ibudilast (3 mg/kg) caused a longer TTO than ASA (300 mg/kg) alone, without significant extension of BT and gastric mucosal injury as observed in ASA (300 mg/kg). These results indicate that the combination of low-dose ASA and ibudilast has a more potent antithrombotic effect than ASA alone without increasing bleeding tendency and gastric mucosal injury. The potent in vivo antithrombotic effect of this combination may be brought about by an action that is associated with PDE4 inhibition of ibudilast. © Georg Thieme Verlag KG Stuttgart · New York.

Use of a student support group to reduce student stress in a nurse anesthesia program.

PubMed

Kless, J R

1989-02-01

Stress in nurse anesthesia programs may be excessive at times, especially in new students. While some degree of stress is necessary to motivate learning, excessive or prolonged stress can interfere with the normal learning process, thereby prolonging a student's clinical and academic progress. In the extreme, excessive stress may even preclude a student's successful completion of the educational program. Active faculty intervention through a student support group is advocated as a method for controlling stress levels and facilitating student learning. The positive effects of such intervention also increase the overall productivity of a program and better prepare nurse anesthesia students for their future careers.

Prolonged and tunable residence time using reversible covalent kinase inhibitors

PubMed Central

Bradshaw, J. Michael; McFarland, Jesse M.; Paavilainen, Ville O.; Bisconte, Angelina; Tam, Danny; Phan, Vernon T.; Romanov, Sergei; Finkle, David; Shu, Jin; Patel, Vaishali; Ton, Tony; Li, Xiaoyan; Loughhead, David G.; Nunn, Philip A.; Karr, Dane E.; Gerritsen, Mary E.; Funk, Jens Oliver; Owens, Timothy D.; Verner, Erik; Brameld, Ken A.; Hill, Ronald J.; Goldstein, David M.; Taunton, Jack

2015-01-01

Drugs with prolonged, on-target residence time often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here, we demonstrate progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Utilizing an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrate biochemical residence times spanning from minutes to 7 days. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK more than 18 hours after clearance from the circulation. The inverted cyanoacrylamide strategy was further utilized to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating generalizability of the approach. Targeting noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates “residence time by design”, the ability to modulate and improve the duration of target engagement in vivo. PMID:26006010

Effects of Appropriate Prolonged Sacral Neuromodulation Testing in Improving Implantation Rate of a Permanent Implantable Pulse Generator in Patients with Refractory Lower Urinary Tract Dysfunctions in Mainland China.

PubMed

Zhang, Peng; Zhang, Jian-Zhong; Wu, Li-Yang; Zhang, Xiao-Dong

2017-02-20

Sacral neuromodulation (SNM) has become an effective method for treating lower urinary tract voiding dysfunction during the past 20 years. Because of the expensive cost, the number of implantable pulse generator (IPG) implantations per year in China is far lower than that in Western developed countries since 2012. This study was to summarize the effects of the appropriate prolonged SNM testing time in improving the implantation rate of a permanent IPG in patients with refractory lower urinary tract symptoms (LUTS) in mainland China. From January 2013 to June 2016, 51 patients with refractory LUTS received SNM therapy. In this study, we compared the conversion rate 2 weeks after the Stage I test and final actual conversion rate. We also observed the complications (such as pain, infection, and electrode displacement) and effectiveness. We tried to improve an appropriate prolonged test time which was favorable for improving the SNM conversion rate while ensuring safety and effectiveness. Among 51 patients receiving SNM therapy, 19 patients (mean age 45.0 ± 16.9 years) had poor Stage I test results, and on an average, the electrode was removed 27.4 ± 9.6 days after the surgery. In one patient, the electrode was removed within 2 weeks; when the remaining 18 patients were questioned 2 weeks after testing, none of the patients wanted to terminate the test, and all the 18 patients desired to prolong the testing time to further observe the treatment effect. The remaining 32 patients (mean age 46.7 ± 15.3 years) received Stage II permanent implantation at 19.6 ± 10.4 days after the surgery. The overall Stage I-II conversion was 62.7% (32/51) in this study. Within 2 weeks after the surgery, only eight patients received Stage II permanent implantation, and the conversion rate was only 15.7% (8/51), which was much lower than the overall conversion rate of 62.7%. Nearly 84.4% (27/32) of the patients received Stage II implantation within 4 weeks. None of the patients had incision infections. In one patient, the entire system was removed 1 month after Stage II implantation due to pain in the implantation site. Appropriate extension of the Stage I testing time of an SNM-barbed electrode could significantly improve the Stage II permanent implantation rate in Chinese refractory LUTS patients; there were no wound infections, and the postoperative complication rate was low. This study recommended that Stage I period of SNM therapy should be 4 weeks according to safety and successful conversion rate.

Delay in reviewing test results prolongs hospital length of stay: a retrospective cohort study.

PubMed

Ong, Mei-Sing; Magrabi, Farah; Coiera, Enrico

2018-05-16

Failure in the timely follow-up of test results has been widely documented, contributing to delayed medical care. Yet, the impact of delay in reviewing test results on hospital length of stay (LOS) has not been studied. We examine the relationship between laboratory tests review time and hospital LOS. A retrospective cohort study of inpatients admitted to a metropolitan teaching hospital in Sydney, Australia, between 2011 and 2012 (n = 5804). Generalized linear models were developed to examine the relationship between hospital LOS and cumulative clinician read time (CRT), defined as the time taken by clinicians to review laboratory test results performed during an inpatient stay after they were reported in the computerized test reporting system. The models were adjusted for patients' age, sex, and disease severity (measured by the Charlson Comorbidity index), the number of test panels performed, the number of unreviewed tests pre-discharge, and the cumulative laboratory turnaround time (LTAT) of tests performed during an inpatient stay. Cumulative CRT is significantly associated with prolonged LOS, with each day of delay in reviewing test results increasing the likelihood of prolonged LOS by 13.2% (p < 0.0001). Restricting the analysis to tests with abnormal results strengthened the relationship between cumulative CRT and prolonged LOS, with each day of delay in reviewing test results increasing the likelihood of delayed discharge by 33.6% (p < 0.0001). Increasing age, disease severity and total number of tests were also significantly associated with prolonged LOS. Increasing number of unreviewed tests was negatively associated with prolonged LOS. Reducing unnecessary hospital LOS has become a critical health policy goal as healthcare costs escalate. Preventing delay in reviewing test results represents an important opportunity to address potentially avoidable hospital stays and unnecessary resource utilization.

13C-sodium acetate breath test for evaluation of gastric emptying times in dogs with gastric dilatation-volvulus.

PubMed

Schmitz, S; Jansen, N; Failing, K; Neiger, R

2013-01-01

The aim of the study was to assess solid phase gastric emptying via non-invasive 13C-sodium acetate breath test in large breed dogs with or without gastric dilatation-volvulus (GDV). Dogs were recruited into one of the following groups: group 1 = healthy large breed dogs with no history of GDV, group 2 = dogs that underwent elective abdominal surgery for reasons unrelated to the gastrointestinal tract, and group 3 = dogs that underwent laparotomy and gastropexy to correct GDV. The dogs were fed a test meal containing 100 mg 13C-sodium acetate (for group 2 and 3, this was < 48 hours post-operatively). Breath samples were obtained at baseline and every 30 minutes for 3 hours, then every hour for a total of 7 hours. 12CO2/13CO2 ratio was measured for each breath sample via non-dispersive infrared spectroscopy and 25%, 50% and 75% gastric emptying times were calculated and compared between groups. Gastric emptying times were significantly prolonged in dogs undergoing surgery (group 2) compared to group 1 and 3. Also, gastric emptying times of dogs with GDV were significantly prolonged compared to controls, but not to the same extent as dogs in group 2. There was a significant effect of abdominal surgery on gastric emptying times. Surprisingly, dogs after GDV surgery and gastropexy had shorter gastric emptying times than dogs undergoing laparotomy for reasons other than GDV, but still prolonged compared to healthy controls. The reason for these differences requires further study.

An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus.

PubMed

Min, Soon-Ki; Kwon, Oh-Choon; Lee, Sub; Park, Ki-Hyuk; Kim, Jong-Ki

2012-05-01

The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p < 0.01). The total inhibition of thrombus formation was observed for unfractionated Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 ± 1.7 min (p < 0.02). In contrast the heparin-treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans. Copyright © 2011 John Wiley & Sons, Ltd.

Changes in Quadriceps Muscle Activity During Sustained Recreational Alpine Skiing

PubMed Central

Kröll, Josef; Müller, Erich; Seifert, John G.; Wakeling, James M.

2011-01-01

During a day of skiing thousands of repeated contractions take place. Previous research on prolonged recreational alpine skiing show that physiological changes occur and hence some level of fatigue is inevitable. In the present paper the effect of prolonged skiing on the recruitment and coordination of the muscle activity was investigated. Six subjects performed 24 standardized runs. Muscle activity during the first two (PREskiing) and the last two (POSTskiing) runs was measured from the vastus lateralis (VL) and rectus femoris (RF) using EMG and quantified using wavelet and principal component analysis. The frequency content of the EMG signal shifted in seven out of eight cases significantly towards lower frequencies with highest effects observed for RF on outside leg. A significant pronounced outside leg loading occurred during POSTskiing and the timing of muscle activity peaks occurred more towards turn completion. Specific EMG frequency changes were observed at certain time points throughout the time windows and not over the whole double turn. It is suggested that general muscular fatigue, where additional specific muscle fibers have to be recruited due to the reduced power output of other fibers did not occur. The EMG frequency decrease and intensity changes for RF and VL are caused by altered timing (coordination) within the turn towards a most likely more uncontrolled skiing technique. Hence, these data provide evidence to suggest recreational skiers alter their skiing technique before a potential change in muscle fiber recruitment occurs. Key points The frequency content of the EMG signal shifted in seven out of eight cases significantly towards lower frequencies with highest effects observed for RF. General muscular fatigue, where additional specific fibers have to be recruited due to the reduced power output of other fibers, did not occur. A modified skiing style towards a less functional and hence more uncontrolled skiing technique seems to be a key issue with respect to the influence on muscle recruitment for applied prolonged skiing session. PMID:24149299

A comparative dose-effect study with cardiac glycosides assessing cardiac and extracardiac responses in normal subjects.

PubMed

Alken, R G; Belz, G G

1984-01-01

We tested the hypothesis that differences exist in the pharmacodynamic pattern of different cardiac glycosides. We conducted a randomized, placebo-controlled study in normal volunteers and evaluated the effects of weekly increased oral dosing of digoxin (n = 10; from 0.25 to 1.0 mg/day), meproscillarin (n = 10; from 0.5 to 2.0 mg/day), and placebo (n = 5). To determine the glycoside effects, corrected electromechanical systole (QS2c) was used to measure inotropy and the PQ interval to test dromotropy. Red-green discrimination and critical flicker fusion (CFF) assessed visual functions. Subjective complaints were collected using rating lists. Both glycosides dose dependently shortened QS2c and prolonged PQ interval. PQ prolongations over +20 ms occurred in seven of 10 digoxin subjects, in two of 10 meproscillarin, and in one of five placebo. Equi-inotropic response, identified at 12 ms mean QS2c shortening, revealed the relative potency of digoxin to be 2.4 times higher than meproscillarin; this ratio increased to sevenfold for equi-effective negative dromotropic effects at 12 ms mean PQ prolongation. Each drug was associated with a dominant subjective complaint: digoxin with anergy and meproscillarin with diarrhea. Red-green discrimination was better under meproscillarin and CFF was depressed by digoxin. The results indicate that pharmacodynamic differences exist between cardiac glycosides. A differential use of various glycosides should be considered and tested clinically.

A Double-Blinded Randomized Clinical Study on the Therapeutic Effect of Gastrografin in Prolonged Postoperative Ileus After Elective Colorectal Surgery.

PubMed

Biondo, Sebastiano; Miquel, Jordi; Espin-Basany, Eloy; Sanchez, Jose Luis; Golda, Thomas; Ferrer-Artola, Ana Maria; Codina-Cazador, Antonio; Frago, Ricardo; Kreisler, Esther

2016-01-01

Postoperative ileus is a common problem with significant clinical and economic consequences. We hypothesized that Gastrografin may have therapeutic utility by accelerating the recovery of postoperative ileus after colorectal surgery. The aim of this trial was to study the impact of oral Gastrografin administration on postoperative prolonged ileus (PPI) after elective colorectal surgery. The main endpoint of this randomized, double-blinded, controlled trial was time of resolution of PPI. The secondary endpoints were overall hospital length of stay, time to start oral intake, time to first passage of flatus or stools, time of need of nasogastric tube, and need of parenteral nutrition. Included criteria were patients older than 18 years, operated for colonic neoplasia, inflammatory bowel disease, or diverticular disease. There were two treatments: Gastrografin administration and placebo. The sample size was calculated taking into account the average length of postoperative ileus after colorectal resection until tolerance to oral intake. Statistical analysis showed that 29 subjects in each group were needed. Twenty-nine patients per group were randomized. Groups were comparable for age, gender, ASA Physical Status Classification System, stoma construction, and surgical technique. No statistical differences were observed in mean time to resolution between the two groups, 9.1 days (CI 95%, 6.51-11.68) in Gastrografin group versus 10.3 days (CI 6.96-10.29) in Placebo group (P = 0.878). Even if not statistically significant, time of resolution of PPI, overall length of stay, time of need of nasogastric tube, and time to tolerance of oral intake were shorter in the G group. Gastrografin does not accelerate significantly the recovery of prolonged postoperative ileus after elective colorectal resection when compared with placebo. However, it seems to clinically improve all the analyzed variables.

Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection.

PubMed

Wan, Shu-Wen; Chen, Pei-Wei; Chen, Chin-Yu; Lai, Yen-Chung; Chu, Ya-Ting; Hung, Chia-Yi; Lee, Han; Wu, Hsuan Franziska; Chuang, Yung-Chun; Lin, Jessica; Chang, Chih-Peng; Wang, Shuying; Liu, Ching-Chuan; Ho, Tzong-Shiann; Lin, Chiou-Feng; Lee, Chien-Kuo; Wu-Hsieh, Betty A; Anderson, Robert; Yeh, Trai-Ming; Lin, Yee-Shin

2017-10-15

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti-DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host-cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.

PubMed

Lenssen, Ton A F; van Steyn, Mike J A; Crijns, Yvonne H F; Waltjé, Eddie M H; Roox, George M; Geesink, Ruud J T; van den Brandt, Piet A; De Bie, Rob A

2008-04-29

Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Although results indicate that prolonged CPM use might have a small short-term effect on RoM, routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered, since neither long-term effects nor transfer to better functional performance was detected. ISRCTN85759656.

Acute effects of unilateral temporary stellate ganglion block on human atrial electrophysiological properties and atrial fibrillation inducibility.

PubMed

Leftheriotis, Dionyssios; Flevari, Panayota; Kossyvakis, Charalampos; Katsaras, Dimitrios; Batistaki, Chrysanthi; Arvaniti, Chrysa; Giannopoulos, Georgios; Deftereos, Spyridon; Kostopanagiotou, Georgia; Lekakis, John

2016-11-01

In experimental models, stellate ganglion block (SGB) reduces the induction of atrial fibrillation (AF), while data in humans are limited. The aim of this study was to assess the effect of unilateral SGB on atrial electrophysiological properties and AF induction in patients with paroxysmal AF. Thirty-six patients with paroxysmal AF were randomized in a 2:1 order to temporary, transcutaneous, pharmaceutical SGB with lidocaine or placebo before pulmonary vein isolation. Lidocaine was 1:1 randomly infused to the right or left ganglion. Before and after randomization, atrial effective refractory period (ERP) of each atrium, difference between right and left atrial ERP, intra- and interatrial conduction time, AF inducibility, and AF duration were assessed. After SGB, right atrial ERP was prolonged from a median (1st-3rd quartile) of 240 (220-268) ms to 260 (240-300) ms (P < .01) and left atrial ERP from 235 (220-260) ms to 245 (240-280) ms (P < .01). AF was induced by atrial pacing in all 24 patients before SGB, but only in 13 patients (54%) after the intervention (P < .01). AF duration was shorter after SGB: 1.5 (0.0-5.8) minutes from 5.5 (3.0-12.0) minutes (P < .01). Intra- and interatrial conduction time was not significantly prolonged. No significant differences were observed between right and left SGB. No changes were observed in the placebo group. Unilateral temporary SGB prolonged atrial ERP, reduced AF inducibility, and decreased AF duration. An equivalent effect of right and left SGB on both atria was observed. These findings may have a clinical implication in the prevention of drug refractory and postsurgery AF and deserve further clinical investigation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Symptom Severity Predicts Prolonged Recovery after Sport-Related Concussion: Age and Amnesia Do Not

PubMed Central

Meehan, William P.; Mannix, Rebekah C.; Stracciolini, Andrea; Elbin, R.J.; Collins, Michael W.

2013-01-01

Objective To identify predictors of prolonged symptoms for athletes who sustain concussions. Study design We conducted a multi-center, prospective, cohort study of patients in 2 sport concussion clinics. Possible predictors of prolonged symptoms from concussion were compared between two groups: those whose symptoms resolved within 28 days and those whose symptoms persisted beyond 28 days. Candidate predictor variables were entered into a logistic regression model that was used to generate adjusted odds ratios. Results During the study period, 182 patients met inclusion criteria. The mean age was 15.2 years (SD 3.04 years). Over a third (N=65) of patients underwent computerized neurocognitive testing on their initial visit. In univariate analyses, Post Concussion Symptom Scale (PCSS) score and all composite scores on computerized neurocognitive testing appeared to be associated with prolonged symptom duration. Sex, age, loss of consciousness at time of injury and amnesia at time of injury were not associated with prolonged symptom duration. After adjusting for potential confounding, however, only total score on the PCSS score was associated with the odds of suffering prolonged symptoms. Conclusions After adjusting for other potential confounding variables, only total score on the PCSS was associated with the odds of suffering prolonged symptoms from sport-related concussions; age and amnesia were not. Further efforts to develop clinical tools for predicting which athletes will suffer prolonged recoveries after concussion should focus on initial symptom score. PMID:23628374

Pilonidal Cyst

MedlinePlus

... for prolonged periods of time, such as truck drivers, are at higher risk of developing a pilonidal ... common in people in their 20s) Obesity Inactive lifestyle Occupation requiring prolonged sitting Excess body hair Stiff ...

The effect of different methods of leucoreduction on plasma coagulation factors.

PubMed

Aboul Enein, Azza A; Abdel Rahman, Hala A; Abdel Maged, Mohamed M M; El Sissy, Maha H

2017-03-01

Removal of leucocytes from blood products, namely leucoreduction, improves the safety of blood transfusion by reducing adverse events associated with the incidental transfusion of leucocytes. Coagulation factors might be compromised during leucoreduction because of exposure of plasma to a variety of filter materials. The aim of the current study was to assess the effect of different methods of prestorage leucofiltration (apheresis and whole blood filters) on prothrombin time, international normalized ratio, partial thromboplastin time and factors V and VIII. There was a significant prolongation of prothrombin time as well as elevation of international normalized ratio in plasma after leucoreduction (14.5 ± 0.7 s vs. 13.9 ± 0.7 s, P = 0.008 and 1.14 ± 0.07 vs. 1.09 ± 0.07, P = 0.005, respectively). Also, there was a statistically significant prolongation of activated partial thromboplastin time in nonleucoreduced plasma (55.6 ± 9.9 s vs. 43.2 ± 12.8 s, P = 0.001). There was no significant filtration effect on factors V and VIII levels. Furthermore, there was no significant difference in factors V and VIII levels between plasma filtered by inline whole blood filters and apheresis machine. Leucodepleted plasma originating from both inline whole blood filter and apheresis machine maintained satisfactory levels of factors V and VIII.

Gene-environment interaction between SCN5A-1103Y and hypokalemia influences QT interval prolongation in African Americans: the Jackson Heart Study.

PubMed

Akylbekova, Ermeg L; Payne, John P; Newton-Cheh, Christopher; May, Warren L; Fox, Ervin R; Wilson, James G; Sarpong, Daniel F; Taylor, Herman A; Maher, Joseph F

2014-01-01

African-American ancestry, hypokalemia, and QT interval prolongation on the electrocardiogram are all risk factors for sudden cardiac death (SCD), but their interactions remain to be characterized. SCN5A-1103Y is a common missense variant, of African ancestry, of the cardiac sodium channel gene. SCN5A-1103Y is known to interact with QT-prolonging factors to promote ventricular arrhythmias in persons at high risk for SCD, but its clinical impact in the general African-American population has not been established. We genotyped SCN5A-S1103Y in 4,476 participants of the Jackson Heart Study, a population-based cohort of African Americans. We investigated the effect of SCN5A-1103Y, including interaction with hypokalemia, on QT interval prolongation, a widely-used indicator of prolonged myocardial repolarization and predisposition to SCD. We then evaluated the two sub-components of the QT interval: QRS duration and JT interval. The carrier frequency for SCN5A-1103Y was 15.4%. SCN5A-1103Y was associated with QT interval prolongation (2.7 milliseconds; P < .001) and potentiated the effect of hypokalemia on QT interval prolongation (14.6 milliseconds; P = .02). SCN5A-1103Y had opposing effects on the two sub-components of the QT interval, with shortening of QRS duration (-1.5 milliseconds; P = .001) and prolongation of the JT interval (3.4 milliseconds; P < .001). Hypokalemia was associated with diuretic use (78%; P < .001). SCN5A-1103Y potentiates the effect of hypokalemia on prolonging myocardial repolarization in the general African-American population. These findings have clinical implications for modification of QT prolonging factors, such as hypokalemia, in the 15% of African Americans who are carriers of SCN5A-1103Y. © 2014.

Topical Drug Formulations for Prolonged Corneal Anesthesia

PubMed Central

Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

2013-01-01

Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

Prolonged sedentary time and physical activity in workplace and non-work contexts: a cross-sectional study of office, customer service and call centre employees

PubMed Central

2012-01-01

Background To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts. Methods A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (<100 counts per minute; cpm), in prolonged sedentary bouts (≥20 minutes or ≥30 minutes), light-intensity activity (100–1951 cpm) and moderate-to-vigorous physical activity (MVPA; ≥1952 cpm). Using mixed models adjusted for confounders, these were compared for: work days versus non-work days; work hours versus non-work hours (work days only); and, across workplace settings. Results Working hours were mostly spent sedentary (77.0%, 95%CI: 76.3, 77.6), with approximately half of this time accumulated in prolonged bouts of 20 minutes or more. There were significant (p<0.05) differences in all outcomes between workdays and non-work days, and, on workdays, between work- versus non-work hours. Results consistently showed “work” was more sedentary and had less light-intensity activity, than “non-work”. The period immediately after work appeared important for MVPA. There were significant (p<0.05) differences in all sedentary and activity outcomes occurring during work hours across the workplace settings. Call-centre workers were generally the most sedentary and least physically active at work; customer service workers were typically the least sedentary and the most active at work. Conclusion The workplace is a key setting for prolonged sedentary time, especially for some occupational groups, and the potential health risk burden attached requires investigation. Future workplace regulations and health promotion initiatives for sedentary occupations to reduce prolonged sitting time should be considered. PMID:23101767

[Arginase Level in Suspended Red Blood Cells Storaged for Different Time].

PubMed

Fan, Li-Ping; Huang, Hao-Bo; Wei, Shi-Jin; Fu, Dan-Hui; Zeng, Feng; Huang, Qing-Hua; Hong, Jin-Quan

2015-10-01

To explore the effect of storage time on arginase level, and the possible source of arginase in suspended red blood cells (RBC). The arginase and myeloperoxidase (MPO) levels in suspended RBC and control plasma were detected by ELISA. The free hemoglobin level in suspended RBC and control plasma were detected by colorimetric method. The relationship between arginase level, MPO level and free hemoglobin level in suspended RBC was analyzed by the related methods. The arginase and free hemoglobin levels in suspended RBC were higher than those in control plasma. Otherwise, MPO level was not significantly different between suspended RBC and control plasma. All of them did not increase along with prolonging of storage time. There was not a significant correlation between arginase level and free hemoglobin level in suspended RBC of different storage time (r = 0.03), but arginase level positively correlated with MPO level in the suspended RBC of different storage time (r = 0.76). The arginase level in suspended RBC storaged for different time increases significantly, but not along with prolonging of storage time. The main possible source of arginase in the suspended RBC is the residual white blood cell, especially neutrophils.

Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

PubMed

Al-Yahya, A M; Al-Masri, A A; El Eter, E A; Hersi, A; Lateef, R; Mawlana, O

2018-05-01

Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

Yogurt Feeding Induced the Prolongation of Fully Major Histocompatibility Complex-Mismatched Murine Cardiac Graft Survival by Induction of CD4+Foxp3+ Cells.

PubMed

Uchiyama, M; Yin, E; Yanagisawa, T; Jin, X; Hara, M; Matsuyama, S; Imazuru, T; Uchida, K; Kawamura, M; Niimi, M

Yogurt is a nutrient-rich food and the beneficial effects of yogurt on both health and immunomodulatory effects are well documented. In this pilot study, we investigated the effects of commercially produced yogurt R-1 on alloimmune responses in a murine cardiac transplantation model. The R-1 is produced by Meiji Co., Ltd., and contains live and active lactic acid bacteria (lactobacillus bulgaricus OLL1073R-1) mainly. CBA (H2 k ) mice underwent transplantation of a C57BL/6 (H2 b ; B6) heart and received oral administration of 1 mL, 0.1 mL, and 0.01 mL of R-1 from the day of transplantation until 7 days afterward. Additionally, we prepared one group of CBA recipients given 1 mL of R-1 sterilized by microwave for 7 days. Histological and immunohistochemical studies were performed. Naïve CBA mice rejected B6 cardiac graft acutely (median survival time [MST]: 7 days). CBA recipients given of 1 mL of R-1 had significantly prolonged B6 allograft survival (MST, 27 days). However, other doses of 0.1 mL and 0.01 mL of R-1 did not prolonged allograft survival (MSTs, 9 days and 8.5 days, respectively). Also, CBA recipients administered microwaved R-1 had no prolongation of B6 allograft (MST, 9 days). Histological and immunohistochemical studies showed the cardiac allograft from R-1-exposed CBA recipients had preserved graft and vessel structure and the number of infiltrated CD4 + , CD8 + , and Foxp3 + cells in R-1-exposed CBA recipients increased, respectively. In conclusion, our findings imply that yogurt containing active lactic acid bacteria could change alloimmune responses partially and induce the prolongation of cardiac allograft survival via CD4 + Foxp3 + regulatory cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Age-dependent inhibition of pentobarbital sleeping time by ozone in mice and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canada, A.T.; Calabrese, E.J.; Leonard, D.

1986-09-01

The effect of age on the metabolism of pentobarbital in mice and rats was investigated following exposure to 0.3 ppm of ozone for 3.75 hr. Young animals were 2.5 months of age and the mature were 18 months. The pentobarbital sleeping time was significantly prolonged following the ozone exposure in both the mice and rats when compared with an air control. No ozone effect on sleeping time was found in the young animals. The results indicate that there may be an age-related sensitivity to the occurrence of ozone-related inhibition of pentobarbital metabolism.

Impact of time to return of spontaneous circulation on neuroprotective effect of targeted temperature management at 33 or 36 degrees in comatose survivors of out-of hospital cardiac arrest.

PubMed

Kjaergaard, Jesper; Nielsen, Niklas; Winther-Jensen, Matilde; Wanscher, Michael; Pellis, Tommaso; Kuiper, Michael; Hartvig Thomsen, Jakob; Wetterslev, Jørn; Cronberg, Tobias; Bro-Jeppesen, John; Erlinge, David; Friberg, Hans; Søholm, Helle; Gasche, Yvan; Horn, Janneke; Hovdenes, Jan; Stammet, Pascal; Wise, Matthew P; Åneman, Anders; Hassager, Christian

2015-11-01

Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC. In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days. Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM. Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Quality assurance in the pre-analytical phase of human urine samples by (1)H NMR spectroscopy.

PubMed

Budde, Kathrin; Gök, Ömer-Necmi; Pietzner, Maik; Meisinger, Christine; Leitzmann, Michael; Nauck, Matthias; Köttgen, Anna; Friedrich, Nele

2016-01-01

Metabolomic approaches investigate changes in metabolite profiles, which may reflect changes in metabolic pathways and provide information correlated with a specific biological process or pathophysiology. High-resolution (1)H NMR spectroscopy is used to identify metabolites in biofluids and tissue samples qualitatively and quantitatively. This pre-analytical study evaluated the effects of storage time and temperature on (1)H NMR spectra from human urine in two settings. Firstly, to evaluate short time effects probably due to acute delay in sample handling and secondly, the effect of prolonged storage up to one month to find markers of sample miss-handling. A number of statistical procedures were used to assess the differences between samples stored under different conditions, including Projection to Latent Structure Discriminant Analysis (PLS-DA), non-parametric testing as well as mixed effect linear regression analysis. The results indicate that human urine samples can be stored at 10 °C for 24 h or at -80 °C for 1 month, as no relevant changes in (1)H NMR fingerprints were observed during these time periods and temperature conditions. However, some metabolites most likely of microbial origin showed alterations during prolonged storage but without facilitating classification. In conclusion, the presented protocol for urine sample handling and semi-automatic metabolite quantification is suitable for large-scale epidemiological studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Cold intermittent cardioplegia reduces the acidosis during prolonged cardiac surgery with cardiopulmonary bypass.

PubMed

Nollo, Giandomenico; Ferrari, Paolo; Graffigna, Angelo C

2011-01-01

The effect on acid-base balance efficacy of intermittent warm and cold blood cardioplegia (IWBC, ICBC) was assessed in 44 patients who underwent cardiac surgery with prolonged aortic cross clamping. With this purpose a customized multi sensor probe was inserted in the coronary sinus, and pH, PO(2), PCO(2) and temperature were continuously measured at 1 Hz sampling rate. The mean cross-clamping time was of 76 ± 26 min on 19 IWBC cases and of 80 ± 24 min on 14 ICBC cases. With IWBC perfusion, at the end of every ischemic period, the lowest pH and PO(2) progressively decreased and the maximal PCO(2) increased. During ICBC the minimum of pH and PO(2) and maximum of PCO2 at the end of different ischemic period during time were constant, also during long cross-clamping time. With IWBC, myocardial ischemia seemed not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO(2) and pH after each reperfusion.

Parental Internet Use and Lifestyle Factors as Correlates of Prolonged Screen Time of Children in Japan: Results From the Super Shokuiku School Project.

PubMed

Yamada, Masaaki; Sekine, Michikazu; Tatsuse, Takashi

2018-03-24

Prolonged screen time (ST), which includes TV viewing and gaming on smartphones and computers, is linked to poor health. Our aim was to explore the associations between school children with prolonged ST and parental internet use (IU) and lifestyles in Japan. Children aged 6 to 13 years from the Super Shokuiku School Project, were surveyed using questionnaires in 2016. The survey assessed the grade, sex, and lifestyle of 1,659 children and parental internet use (IU) and lifestyle using Breslow's seven health behaviors. IU consisted of internet surfing and gaming on personal computers (PC), smartphones, or consoles. Three or more hours of ST was defined as prolonged ST, and its correlates were analyzed using logistic regression. Of all, 643 (38.8%) children spent ≥2 hours/day of ST on a week day, whilst 153 (9.2%) children spent ≥3 hours/day. Prolonged ST was significantly associated with children in higher grade (odds ratio [OR] 1.74; 95% confidence interval [CI], 1.20-2.51), boys (OR 2.16; 95% CI, 1.49-3.14), skipping breakfast (OR 1.88; 95% CI, 1.05-3.35), late bedtime (OR 1.80; 95% CI, 1.15-2.82), physical inactivity (OR 1.79; 95% CI, 1.12-2.87), father's IU ≥2 hours/day (OR 2.35; 95% CI, 1.52-3.63), mother's prolonged IU ≥2 hours/day (OR 2.55; 95% CI, 1.43-4.52), mothers with unhealthy behaviors (OR 1.81; 95% CI, 1.05-3.13), no rule setting governing screen time (OR 2.41; 95% CI, 1.63-3.58), and mothers with full-time employment (OR 1.95; 95% CI, 1.06-3.64). Prolonged ST among Japanese children was strongly associated with parental IU, no set rules for ST, and mother's unhealthy lifestyles. To reduce children's ST, parental engagement is warranted in the intervention strategy.

Prevalence, Risk Factors and In-hospital Outcomes of QTc Interval Prolongation in Liver Cirrhosis.

PubMed

Zhao, Jiancheng; Qi, Xingshun; Hou, Feifei; Ning, Zheng; Zhang, Xintong; Deng, Han; Peng, Ying; Li, Jing; Wang, Xiaoxi; Li, Hongyu; Guo, Xiaozhong

2016-09-01

QTc interval prolongation is an electrocardiographic abnormality in liver cirrhosis. The objective of this study was to evaluate the prevalence, risk factors and in-hospital outcomes of QTc interval prolongation in Chinese patients with liver cirrhosis. This was a retrospective analysis of a total of 1,268 patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and June 2014. QTc interval data were collected from the medical records. QTc interval prolongation was defined as QTc interval > 440 milliseconds. The prevalence of QTc interval prolongation was 38.2% (485 of 1268). In the entire cohort, the risk factors for QTc interval prolongation included an older age, a higher proportion of alcohol abuse and ascites, higher bilirubin, blood urea nitrogen, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower red blood cell (RBC), hemoglobin (Hb), albumin (ALB), alanine aminotransferase and calcium. The in-hospital mortality was not significantly different between patients with and without QTc interval prolongation (2.1% versus 1.3%, P = 0.276). In the subgroup analyses of patients with hepatitis B virus or alcohol alone-related liver cirrhosis, the risk factors included higher bilirubin, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower RBC, Hb and ALB. In the subgroups analyses of patients with acute upper gastrointestinal bleeding or ascites, the risk factors included lower RBC, Hb and ALB. QTc interval prolongation was frequent in liver cirrhosis. Although QTc interval prolongation was positively associated with alcohol-related liver cirrhosis and more severe liver dysfunction, it did not significantly influence the in-hospital mortality. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Improvement of exposure times: effects on adhesive properties and resin-dentin bond strengths of etch-and-rinse adhesives.

PubMed

Ferreira, Sabrina Queji; Costa, Thays Regina; Klein-Júnior, Celso Afonso; Accorinte, Maria de; Meier, Márcia Margarete; Loguercio, Alessandro Dourado; Reis, Alessandra

2011-06-01

This study evaluated the effect of prolonged polymerization times on the microtensile resin-dentin bond strength (μTBS), degree of conversion of adhesive films (DC) and silver nitrate uptake (SNU) for an ethanol/water- (Adper Single Bond 2, [SB]) and an acetone-based (One Step Plus, [OS]) etch-and-rinse adhesive. Thirty caries-free extracted molars were included in this study. The occlusal enamel of all teeth was removed by wet grinding the occlusal enamel on 180-grit SiC paper. Adhesives were applied according to the manufacturer's instructions, but they were light cured for 10, 20 and 40 s at 600 mW/cm2. Bonded sticks (0.6 mm2) were tested in tension (0.5 mm/min). Two bonded sticks from each tooth were immersed in an ammoniacal solution of silver nitrate (24 h), photodeveloped (8 h), and analyzed by SEM. The DC of the adhesives was evaluated under Fourier Transformed Infra-Red spectroscopy (FTIR). Data for each property were analyzed by two-way ANOVA and Tukey's test (α = 0.05). Statistically higher μTBS and DC were observed for SB and OS when both adhesives were light cured for 40 s in comparison with 10 s. For OS, the μTBS in the 20- and 40-s groups did not differ statistically, while for SB it did. Higher prolonged exposure times did not prevent nanoleakage within the hybrid layer for all groups regardless of the adhesive. This study supports the hypothesis that exposure times longer than those recommended can improve the degree of conversion of adhesive films and the immediate resin-dentin bonds. The prolonged curing times (20 and 40 s) for polymerization of simplified adhesives resulted in an increase in the degree of conversion of the adhesive films and resin-dentin bond strengths but did not reduce the nanoleakage within the hybrid layer.

Synaptic Plasticity and Memory Formation.

DTIC Science & Technology

1992-05-14

aniracetam which, as shown in an AFOSR sponsored experiment, prolongs the mean open time of the AMPA receptor channel (33). The effects of aniracetam ...potentiation while suppression of the between-burst hyperpolarizatlon elevated the ceiling on maximal LTP (40). The drug aniracetam , which as noted...receptors. Behav. Neural Biol. 54: 213-217, 1990. 23. Staubli, U., Kessler, M. and Lynch, G. Aniracetam has proportionately smaller effects on synapses

Development of a vancomycin dosing approach for critically ill patients receiving hybrid hemodialysis using Monte Carlo simulation.

PubMed

Lewis, Susan J; Mueller, Bruce A

2018-01-01

Prolonged intermittent renal replacement therapy is an increasingly popular treatment for acute kidney injury in critically ill patients that runs at different flow rates and durations than conventional hemodialysis or continuous renal replacement therapies. Pharmacokinetic studies conducted in patients receiving prolonged intermittent renal replacement therapy are scarce; consequently, clinicians are challenged to dose antibiotics effectively. The purpose of this study was to develop vancomycin dosing recommendations for patients receiving prolonged intermittent renal replacement therapy. Monte Carlo simulations were performed in thousands of virtual patients derived from previously published demographic, pharmacokinetic, and dialytic information derived from critically ill patients receiving vancomycin and other forms of renal replacement therapy. We conducted "in silico" vancomycin pharmacokinetic/pharmacodynamics analyses in these patients receiving prolonged intermittent renal replacement therapy to determine what vancomycin dose would achieve vancomycin 24-h area under the curve (AUC 24h ) of 400-700 mg·h/L, a target associated with positive clinical outcomes. Nine different vancomycin dosing regimens were tested using four different, commonly used prolonged intermittent renal replacement therapy modalities. A dosing nomogram based on serum concentration data achieved after the third dose was developed to individualize vancomycin therapy. An initial vancomycin dose of 15 or 20 mg/kg immediately followed by 15 mg/kg after subsequent prolonged intermittent renal replacement therapy treatments achieved AUC 24h of ≥400 mg·h/L for ≥90% of patients regardless of prolonged intermittent renal replacement therapy duration, modality, or time of vancomycin dose relative to prolonged intermittent renal replacement therapy. Many patients experienced AUC 24h of ≥700 mg·h/L, but once the dosing nomogram was applied to serum concentrations obtained after the third vancomycin dose, 67%-88% of patients achieved AUC 24h of 400-700 mg·h/L. An initial loading dose of 15-20 mg/kg followed by a maintenance regimen of 15 mg/kg after every prolonged intermittent renal replacement therapy session coupled with serum concentration monitoring should be used to individualize vancomycin dosing. These predictions need clinical verification.

Survival analysis, long-term outcomes, and percentage of recovery up to 8 years post-infection among the Houston West Nile virus cohort.

PubMed

Murray, Kristy O; Garcia, Melissa N; Rahbar, Mohammad H; Martinez, Diana; Khuwaja, Salma A; Arafat, Raouf R; Rossmann, Susan

2014-01-01

In 2012, we witnessed a resurgence of West Nile virus (WNV) in the United States, with the largest outbreak of human cases reported since 2003. WNV is now endemic and will continue to produce epidemics over time, therefore defining the long-term consequences of WNV infection is critical. Over a period of eight years, we prospectively followed a cohort of 157 WNV-infected subjects in the Houston metropolitan area to observe recovery over time and define the long-term clinical outcomes. We used survival analysis techniques to determine percentage of recovery over time and the effects of demographic and co-morbid conditions on recovery. We found that 40% of study participants continued to experience symptoms related to their WNV infection up to 8 years later. Having a clinical presentation of encephalitis and being over age 50 were significantly associated with prolonged or poor recovery over time. Since the health and economic impact as a result of prolonged recovery, continued morbidity, and related disability is likely substantial in those infected with WNV, future research should be aimed at developing effective vaccines to prevent illness and novel therapeutics to minimize morbidity, mortality, and long-term complications from infection.

Survival Analysis, Long-Term Outcomes, and Percentage of Recovery up to 8 Years Post-Infection among the Houston West Nile Virus Cohort

PubMed Central

Murray, Kristy O.; Garcia, Melissa N.; Rahbar, Mohammad H.; Martinez, Diana; Khuwaja, Salma A.; Arafat, Raouf R.; Rossmann, Susan

2014-01-01

In 2012, we witnessed a resurgence of West Nile virus (WNV) in the United States, with the largest outbreak of human cases reported since 2003. WNV is now endemic and will continue to produce epidemics over time, therefore defining the long-term consequences of WNV infection is critical. Over a period of eight years, we prospectively followed a cohort of 157 WNV-infected subjects in the Houston metropolitan area to observe recovery over time and define the long-term clinical outcomes. We used survival analysis techniques to determine percentage of recovery over time and the effects of demographic and co-morbid conditions on recovery. We found that 40% of study participants continued to experience symptoms related to their WNV infection up to 8 years later. Having a clinical presentation of encephalitis and being over age 50 were significantly associated with prolonged or poor recovery over time. Since the health and economic impact as a result of prolonged recovery, continued morbidity, and related disability is likely substantial in those infected with WNV, future research should be aimed at developing effective vaccines to prevent illness and novel therapeutics to minimize morbidity, mortality, and long-term complications from infection. PMID:25054656

Vision and Vestibular System Dysfunction Predicts Prolonged Concussion Recovery in Children.

PubMed

Master, Christina L; Master, Stephen R; Wiebe, Douglas J; Storey, Eileen P; Lockyer, Julia E; Podolak, Olivia E; Grady, Matthew F

2018-03-01

Up to one-third of children with concussion have prolonged symptoms lasting beyond 4 weeks. Vision and vestibular dysfunction is common after concussion. It is unknown whether such dysfunction predicts prolonged recovery. We sought to determine which vision or vestibular problems predict prolonged recovery in children. A retrospective cohort of pediatric patients with concussion. A subspecialty pediatric concussion program. Four hundred thirty-two patient records were abstracted. Presence of vision or vestibular dysfunction upon presentation to the subspecialty concussion program. The main outcome of interest was time to clinical recovery, defined by discharge from clinical follow-up, including resolution of acute symptoms, resumption of normal physical and cognitive activity, and normalization of physical examination findings to functional levels. Study subjects were 5 to 18 years (median = 14). A total of 378 of 432 subjects (88%) presented with vision or vestibular problems. A history of motion sickness was associated with vestibular dysfunction. Younger age, public insurance, and presence of headache were associated with later presentation for subspecialty concussion care. Vision and vestibular problems were associated within distinct clusters. Provocable symptoms with vestibulo-ocular reflex (VOR) and smooth pursuits and abnormal balance and accommodative amplitude (AA) predicted prolonged recovery time. Vision and vestibular problems predict prolonged concussion recovery in children. A history of motion sickness may be an important premorbid factor. Public insurance status may represent problems with disparities in access to concussion care. Vision assessments in concussion must include smooth pursuits, saccades, near point of convergence (NPC), and accommodative amplitude (AA). A comprehensive, multidomain assessment is essential to predict prolonged recovery time and enable active intervention with specific school accommodations and targeted rehabilitation.

Prolonged sitting in cars: prevalence, socio-demographic variations, and trends.

PubMed

Sugiyama, Takemi; Merom, Dafna; van der Ploeg, Hidde P; Corpuz, Grace; Bauman, Adrian; Owen, Neville

2012-10-01

Prolonged sitting is detrimentally associated with health outcomes. However, the prevalence and characteristics of those who sit in cars for long periods are not well understood. This study examined the population prevalence, socio-demographic variations, and trends for prolonged sitting in cars among adults. Using the Sydney Greater Metropolitan Area Household Travel Survey, the prevalence of prolonged sitting time in cars (≥2 h/day) was calculated for four 3-year periods (1997-99, 2000-02, 2003-05, and 2006-08) for each population subgroup. Trends were calculated as the mean change in prevalence between adjacent survey periods. Cars were used for 66% of the total trips recorded (n=336,505). The prevalence of prolonged sitting time in cars was 16-18% in men, and 10-12% in women. Relatively higher prevalence rates were found among middle-age groups (men: 20-22%, women: 12-15%), full-time workers (men: 21-24%, women: 14-15%), those with higher income (men: 21-25%, women: 14-16%), couples with children (men: 20-21%, women: 12-14%), and those living in outer suburbs (men: 20-23%, women: 12-13%). Trends were stable in men, but increasing in women. Several subgroups (older age; living in regional suburbs) also showed increasing trends. These findings provide evidence to inform integrated approaches to measurement and policy development on prolonged car use among the public health, urban planning, and transport sectors. Copyright © 2012 Elsevier Inc. All rights reserved.

Irreversible modification of sodium channel inactivation in toad myelinated nerve fibres by the oxidant chloramine-T.

PubMed Central

Wang, G K

1984-01-01

The effects of externally applied chloramine-T on the excitability of single toad myelinated nerve fibres were studied. Chloramine-T is a mild oxidant which reacts specifically with the cysteine and methionine residues of proteins. Chloramine-T prolongs the action potential of a single myelinated fibre by more than 1000-fold. This effect is concentration- and time-dependent; higher concentrations and longer incubation times increase prolongation. Under voltage-clamp conditions, sodium channel inactivation is markedly inhibited by chloramine-T while sodium channel activation remains normal. Prolonged depolarization of the membrane leads to a maintained sodium current. The maintained sodium currents show activation kinetics, dependence on membrane potential, and reversal potentials which are similar to those of normal, inactivating sodium currents in untreated fibres. Both the maintained and the peak sodium currents are equally inhibited by tetrodotoxin. After partial removal of sodium inactivation by brief exposures to chloramine-T, the voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by about 20 mV, even after correction for the non-inactivating component contributed by the maintained current. The phenomena described here imply that cysteine or methionine residues are critical for the sodium channel inactivation processes. The two different modifications of inactivation, its removal shown by the maintained current, and the shift in the voltage-dependence of the remaining inactivatable channels, reveal that at least two separate residues are modified by chloramine-T. PMID:6321714

Effects of temperature and calcium availability on ventricular myocardium from rainbow trout.

PubMed

Coyne, M D; Kim, C S; Cameron, J S; Gwathmey, J K

2000-06-01

We studied the mechanical and electrophysiological properties of ventricular myocardium from rainbow trout (Oncorhynchus mykiss) in vitro at 4, 10, and 18 degrees C from fish acclimated at 10 degrees C. Temperature alone did not significantly alter the contractile force of the myocardium, but the time to peak tension and time to 80% relaxation were prolonged at 4 degrees C and shortened at 18 degrees C. The duration of the action potential was also prolonged at 4 degrees C and progressively shortened at higher temperatures. An alteration of the stimulation frequency did not affect contraction amplitude at any temperature. Calcium influx via L-type calcium channels was increased by raising extracellular calcium concentration (¿Ca(2+)(o)) or including Bay K 8644 (Bay K) and isoproterenol in the bathing medium. These treatments significantly enhanced the contractile force at all temperatures. Calcium channel blockers had a reverse-negative inotropic effect. Unexpectedly, the duration of the action potential at 10 degrees C was shortened as ¿Ca(2+)(o) increased. However, Bay K prolonged the plateau phase at 4 degrees C. Caffeine, which promotes the release of sarcoplasmic reticulum (SR) calcium, increased contractile force eightfold at all three temperatures, but the SR blocker ryanodine was only inhibitory at 4 degrees C. Our results suggest that contractile force in ventricular myocardium from Oncorhynchus mykiss is primarily regulated by sarcolemmal calcium influx and that ventricular contractility is maintained during exposure to a wide range of temperatures.

Quality changes of cuttlefish stored under various atmosphere modifications and vacuum packaging.

PubMed

Bouletis, Achilleas D; Arvanitoyannis, Ioannis S; Hadjichristodoulou, Christos; Neofitou, Christos; Parlapani, Foteini F; Gkagtzis, Dimitrios C

2016-06-01

Seafood preservation and its shelf life prolongation are two of the main issues in the seafood industry. As a result, and in view of market globalization, research has been triggered in this direction by applying several techniques such as modified atmosphere packaging (MAP), vacuum packaging (VP) and active packaging (AP). However, seafood such as octopus, cuttlefish and others have not been thoroughly investigated up to now. The aim of this research was to determine the optimal conditions of modified atmosphere under which cuttlefish storage time and consequently shelf life time could be prolonged without endangering consumer safety. It was found that cuttlefish shelf life reached 2, 2, 4, 8 and 8 days for control, VP, MAP 1, MAP 2 and MAP 3 (20% CO2 -80% N2 , 50% CO2 -50% N2 and 70% CO2 -30% N2 for MAP 1, 2 and 3, respectively) samples, respectively, judging by their sensorial attributes. Elevated CO2 levels had a strong microbiostatic effect, whereas storage under vacuum did not offer significant advantages. All physicochemical attributes of MAP-treated samples were better preserved compared to control. Application of high CO2 atmospheres such as MAP 2 and MAP 3 proved to be an effective strategy toward preserving the characteristics and prolonging the shelf life of fresh cuttlefish and thereby improving its potential in the market. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

An e-health intervention designed to increase workday energy expenditure by reducing prolonged occupational sitting habits.

PubMed

Pedersen, Scott J; Cooley, Paul D; Mainsbridge, Casey

2014-01-01

Desk-based employees face multiple workplace health hazards such as insufficient physical activity and prolonged sitting. The objective of this study was to increase workday energy expenditure by interrupting prolonged occupational sitting time and introducing short-bursts of physical activity to employees' daily work habits. Over a 13-week period participants (n=17) in the intervention group were regularly exposed to a passive prompt delivered through their desktop computer that required them to stand up and engage in a short-burst of physical activity, while the control group (n=17) was not exposed to this intervention. Instead, the control group continued with their normal work routine. All participants completed a pre- and post- intervention survey to estimate workplace daily energy expenditure (calories). There was a significant 2 (Group) × 2 (Test) interaction, F (1, 32)=9.26, p < 0.05. The intervention group increased the calories expended during the workday from pre-test (M=866.29 ± 151.40) to post-test (M=1054.10 ± 393.24), whereas the control group decreased calories expended during the workday from pre-test (M=982.55 ± 315.66) to post-test (M=892.21 ± 255.36). An e-health intervention using a passive prompt was an effective mechanism for increasing employee work-related energy expenditure. Engaging employees in regular short-bursts of physical activity during the workday resulted in reduced sitting time, which may have long-term effects on the improvement of employee health.

Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis.

PubMed

Goyer, Isabelle; Ferland, Gabrielle; Ruo, Ni; Morin, Caroline; Brochet, Marie-Sophie; Morin, Lucie; Ferreira, Ema

2016-09-13

Since 2006, the empiric use of azithromycin in women at risk of premature birth has become prevalent in our institution without any evidence of its efficacy. Although antibiotics can prolong pregnancy in preterm prolonged rupture of membranes, no published data are available for women with intact membranes. To describe the purpose of adding azithromycin to the usual treatments (cerclage, tocolysis, rest, etc.) to prolong pregnancy in women with intact membranes who are at risk of or already in preterm labour. A retrospective observational cohort study was done at a Mother-Child University Hospital Centre. Patients admitted to obstetric ward who received azithromycin between January 1 st , 2006 and August 1 st , 2010 were included. A total of 127 exposed women were matched to 127 controls through medical records and pharmacy software. A time-to-event analysis was done to compare gestational age at the time of the recorded composite event (delivery, or rupture of membranes, or second intervention to prolong pregnancy). To compare proportions of composite event at different time points, χ 2 tests were used. Patients who received azithromycin had a more severe condition at presentation. Once adjusted for confounding factors, prolongation of pregnancy (HR =1.049; CI 95%: 0.774-1.421 [p=0.758]) and gestational age at the event (HR=1.200; CI 95%: 0.894-1.609 [p=0.225]) did not differ between the groups. The proportions of women with an event ≥7 days post-diagnosis or ≥37 gestational weeks were similar. Azithromycin was added to medical therapy in a more at-risk population and no clear benefit was measured.

Physiological and performance effects of carbohydrate gels consumed prior to the extra-time period of prolonged simulated soccer match-play.

PubMed

Harper, Liam D; Briggs, Marc A; McNamee, Ged; West, Daniel J; Kilduff, Liam P; Stevenson, Emma; Russell, Mark

2016-06-01

The physiological and performance effects of carbohydrate-electrolyte gels consumed before the 30min extra-time period of prolonged soccer-specific exercise were investigated. Randomised, double-blind, crossover. Eight English Premier League academy soccer players performed 120min of soccer-specific exercise on two occasions while consuming fluid-electrolyte beverages before exercise, at half-time and 90min. Carbohydrate-electrolyte (0.7±0.1gkg(-1) BM) or energy-free placebo gels were consumed ∼5min before extra-time. Blood samples were taken before exercise, at half-time and every 15min during exercise. Physical (15-m and 30-m sprint speed, 30-m sprint maintenance and countermovement jump height) and technical (soccer dribbling) performance was assessed throughout each trial. Carbohydrate-electrolyte gels improved dribbling precision (+29±20%) and raised blood glucose concentrations by 0.7±0.8mmoll(-1) during extra-time (both p<0.01). Supplementation did not affect sprint velocities (15m and 30m), 30-m sprint maintenance or dribbling speed as reductions compared to 0-15min values occurred at 105-120min irrespective of trial (all p<0.05). Plasma osmolality and blood sodium concentrations increased post-exercise vs. the opening 15min (p<0.05) but no effect of supplementation existed. Selected markers of physical performance (jump height, 30-m sprint velocity and 30-m repeated sprint maintenance) also reduced by >3% during half-time (all p<0.05). Carbohydrate-electrolyte gel ingestion raised blood glucose concentrations and improved dribbling performance during the extra-time period of simulated soccer match-play. Supplementation did not attenuate reductions in physical performance and hydration status that occurred during extra-time. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

An Overview On Various Approaches And Recent Patents On Gastroretentive Drug Delivery Systems.

PubMed

Kumar, Manoj; Kaushik, Deepak

2018-03-08

Drugs having absorption window in the stomach or upper small intestine has restricted bioavailability with conventional dosage forms. The gastric residence time of these dosage forms is usually short and they do not show drug release for prolonged period of time. To avoid these problems and to enhance the bioavailability and gastric retention time of these drugs, controlled drug delivery systems with prolonged gastric retention time are currently being developed. This review highlights the various pharmaceutical approaches for gastroretention such as floating drug delivery systems, mucoadhesive systems, high density systems, expandable and swelling systems, superporous hydrogels systems, magnetic systems, ion exchange resin system and recent patents filed or granted for these approaches. Recently some patents are also reported where a combination of various approaches are being employed to achieve very effective gastroretention. The various patent search sites were used to collect and analyze the information on gastroretentive drug delivery systems. The present study provides valuable information, advantages, limitations and future outlook of various gastroretentive drug delivery systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive, physical and physiological responses of school boy cricketers to a 30-over batting simulation.

PubMed

Goble, David; Christie, Candice Jo-Anne

2017-06-01

The purpose of this study was to assess how cognitive and physical performance are affected during a prolonged, fatigue-inducing cricket-batting simulation. Fifteen amateur batters from three Eastern Cape schools in South Africa were recruited (mean ± SD: age 17 ± 0.92 years; stature 1.75 ± 0.07 m; body mass 78.3 ± 13.2 kg). Participants completed a 6-stage, 30-over batting simulation (BATEX © ). During the protocol, there were five periods of cognitive assessment (CogState brief test battery, Melbourne, Australia). The primary outcome measures from each cognitive task were speed and accuracy/error rates. Physiological (heart rate) and physical (sprint times) responses were also recorded. Sprint times deteriorated (d = 0.84; P < 0.01) while physiological responses increased (d = 0.91; P < 0.01) as batting duration increased, with longest times and highest responses occurring in the final stage. Prolonged batting had a large effect on executive task performance (d = 0.85; P = 0.03), and moderate effects on visual attention and vigilance (d = 0.56; P = 0.21) and attention and working memory (d = 0.61; P = 0.11), reducing task performance after 30 overs. Therefore, prolonged batting with repeated shuttle running fatigues amateur batters and adversely affects higher-order cognitive function. This will affect decision-making, response selection, response execution and other batting-related executive processes. We recommend that training should incorporate greater proportions of centre-wicket batting with repeated, high-intensity shuttle running. This will improve batting-related skills and information processing when fatigued, making practice more representative of competition.

Feasibility and acceptability of reducing workplace sitting time: a qualitative study with Australian office workers.

PubMed

Hadgraft, Nyssa T; Brakenridge, Charlotte L; LaMontagne, Anthony D; Fjeldsoe, Brianna S; Lynch, Brigid M; Dunstan, David W; Owen, Neville; Healy, Genevieve N; Lawler, Sheleigh P

2016-09-05

Office workers spend a large proportion of their working hours sitting. This may contribute to an increased risk of chronic disease and premature mortality. While there is growing interest in workplace interventions targeting prolonged sitting, few qualitative studies have explored workers' perceptions of reducing occupational sitting outside of an intervention context. This study explored barriers to reducing office workplace sitting, and the feasibility and acceptability of strategies targeting prolonged sitting in this context. Semi-structured interviews were conducted with a convenience sample of 20 office workers (50 % women), including employees and managers, in Melbourne, Australia. The three organisations (two large, and one small organisation) were from retail, health and IT industries and had not implemented any formalised approaches to sitting reduction. Questions covered barriers to reducing sitting, the feasibility of potential strategies aimed at reducing sitting, and perceived effects on productivity. Interviews were audiotaped and transcribed verbatim. Data were analysed using thematic analysis. Participants reported spending most (median: 7.2 h) of their working hours sitting. The nature of computer-based work and exposure to furniture designed for a seated posture were considered to be the main factors influencing sitting time. Low cost strategies, such as standing meetings and in-person communication, were identified as feasible ways to reduce sitting time and were also perceived to have potential productivity benefits. However, social norms around appropriate workplace behaviour and workload pressures were perceived to be barriers to uptake of these strategies. The cost implications of height-adjustable workstations influenced perceptions of feasibility. Managers noted the need for an evidence-based business case supporting action on prolonged sitting, particularly in the context of limited resources and competing workplace health priorities. While a number of low-cost approaches to reduce workplace sitting are perceived to be feasible and acceptable in the office workplace, factors such as work demands and the organisational social context may still act as barriers to greater uptake. Building a supportive organisational culture and raising awareness of the adverse health effects of prolonged sitting may be important for improving individual-level and organisational-level motivation for change.

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue

PubMed Central

Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C.

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection. PMID:27936002

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

PubMed

Ng, Deborah Hl; Wong, Joshua Gx; Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection.

Determinants of mortality and prolonged hospital stay among dengue patients attending tertiary care hospital: a cross-sectional retrospective analysis

PubMed Central

Khan, Amer Hayat; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Yusra Habib

2017-01-01

Objectives Dengue imposes substantial economic, societal and personal burden in terms of hospital stay, morbidity and mortality. Early identification of dengue cases with high propensity of increased hospital stay and death could be of value in isolating patients in need of early interventions. The current study was aimed to determine the significant factors associated with dengue-related prolonged hospitalisation and death. Design Cross-sectional retrospective study. Setting Tertiary care teaching hospital. Participants Patients with confirmed dengue diagnosis were stratified into two categories on the basis of prolonged hospitalisation (≤3 days and >3 days) and mortality (fatal cases and non-fatal cases). Clinico-laboratory characteristics between these categories were compared by using appropriate statistical methods. Results Of 667 patients enrolled, 328 (49.2%) had prolonged hospitalisation. The mean hospital stay was 4.88±2.74 days. Multivariate analysis showed that dengue haemorrhagic fever (OR 2.3), elevated alkaline phosphatase (ALP) (OR 2.3), prolonged prothrombin time (PT) (OR 1.7), activated partial thromboplastin time (aPTT) (OR 1.9) and multiple-organ dysfunctions (OR 2.1) were independently associated with prolonged hospitalisation. Overall case fatality rate was 1.1%. Factors associated with dengue mortality were age >40 years (p=0.004), secondary infection (p=0.040), comorbidities (p<0.05), acute kidney injury (p<0.001), prolonged PT (p=0.022), multiple-organ dysfunctions (p<0.001), haematocrit >20% (p=0.001), rhabdomyolosis (p<0.001) and respiratory failure (p=0.007). Approximately half of the fatal cases in our study had prolonged hospital stay of greater than three days. Conclusions The results underscore the high proportion of dengue patients with prolonged hospital stay. Early identification of factors relating to prolonged hospitalisation and death will have obvious advantages in terms of appropriate decisions about treatment and management in high dependency units. PMID:28698348

76 FR 73634 - Agency Information Collection Activities: Announcement of Board Approval Under Delegated...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... effects that a prolonged economic downturn could have on their capital adequacy and ability to continue to operate and remain credit intermediaries during times of economic and financial stress. In 2009, the Board... whether large BHCs had capital sufficient to weather a more-adverse-than-anticipated economic environment...

Warfarin hypersensitivity due to gluten-sensitive enteropathy: a case study.

PubMed

Kwolek, Sara; Deming, Paula

2012-01-01

A 53 year old female who was maintained on long-term warfarin therapy due to history of pulmonary embolism, repeatedly presents with an abnormally prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). After many asymptomatic episodes were corrected with Vitamin K therapy to temporarily reverse the effects of the warfarin, the cause of the apparent coagulopathy was further investigated. Factor Activity Assays of the common pathway factors II, IX, and X all revealed critically low values; below the threshold even a loading dose of warfarin is typically capable of eliciting. The patient tested strongly positive for Tissue Transglutaminase IgA, which is highly suggestive of a gluten-sensitive enteropathy. One effect of this condition is malabsorption due to flattened intestinal villi. The patient was determined to have an acquired vitamin K deficiency secondary to gluten-sensitive enteropathy. Her condition was exacerbated by the long-term warfarin therapy, resulting in the prolonged PT and PTT. The patient was treated with vitamin K therapy, which reversed the deficiency and corrected her abnormal coagulation results.

Brain mapping after prolonged cycling and during recovery in the heat.

PubMed

De Pauw, Kevin; Roelands, Bart; Marusic, Uros; Tellez, Helio Fernandez; Knaepen, Kristel; Meeusen, Romain

2013-11-01

The aim of this study was to determine the effect of prolonged intensive cycling and postexercise recovery in the heat on brain sources of altered brain oscillations. After a max test and familiarization trial, nine trained male subjects (23 ± 3 yr; maximal oxygen uptake = 62.1 ± 5.3 ml·min(-1)·kg(-1)) performed three experimental trials in the heat (30°C; relative humidity 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1 h. The first was a 60-min constant-load trial, followed by a 30-min simulated time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, active recovery (AR), passive rest (PR), or cold water immersion (CWI) was applied for 15 min. Electroencephalography was measured at baseline and during postexercise recovery. Standardized low-resolution brain electromagnetic tomography was applied to accurately pinpoint and localize altered electrical neuronal activity. After CWI, PR and AR subjects completed TT2 in 761 ± 42, 791 ± 76, and 794 ± 62 s, respectively. A prolonged intensive cycling performance in the heat decreased β activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in Brodmann areas (BA) 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Postexercise CWI increased β3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.

Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis

PubMed Central

Ju, Bum Jun; Jang, Yoo Kyung; You, Hae Seun; Kang, Hyun; Park, Ji Yong

2017-01-01

Background Tramadol, a 4-phenyl-piperidine analog of codeine, has a unique action in that it has a central opioidergic, noradrenergic, serotonergic analgesic, and peripheral local anesthetic (LA) effect. Many studies have reported contradictory findings regarding the peripheral analgesic effect of tramadol as an adjuvant to LA in brachial plexus block (BPB). This meta-analysis aimed to evaluate the effects of tramadol as an adjunct to LA in BPB during shoulder or upper extremity surgery. Methods We searched the PubMed, EMBASE, Cochrane, KoreaMed databases, and Google Scholar for eligible randomized controlled trials (RCTs) that compared BPB with LA alone and BPB with LA and tramadol. Primary outcomes were the effects of tramadol as an adjuvant on duration of sensory block, motor block, and analgesia. Secondary outcomes were the effects of tramadol as an adjuvant on time to onset of sensory block and motor block and on adverse effects. We performed the meta-analysis using Review Manager 5.3 software. Results We identified 16 RCTs with 751 patients. BPB with tramadol prolonged the duration of sensory block (mean difference [MD], -61.5 min; 95% CI, -95.5 to -27.6; P = 0.0004), motor block (MD, -65.6 min; 95% CI, -101.5 to -29.7; P = 0.0003), and analgesia (MD, -125.5 min; 95% CI, -175.8 to -75.3; P < 0.0001) compared with BPB without tramadol. Tramadol also shortened the time to onset of sensory block (MD, 2.1 min; 95% CI, 1.1 to 3.1; P < 0.0001) and motor block (MD, 1.2 min; 95% CI, 0.2 to 2.1; P = 0.010). In subgroup analysis, the duration of sensory block, motor block, and analgesia was prolonged for BPB with tramadol 100 mg (P < 0.05) but not for BPB with tramadol 50 mg. The quality of evidence was high for duration of analgesia according to the GRADE system. Adverse effects were comparable between the studies. Conclusions In upper extremity surgery performed under BPB, use of tramadol 100 mg as an adjuvant to LA appears to prolong the duration of sensory block, motor block, and analgesia, and shorten the time to onset of sensory and motor blocks without altering adverse effects. PMID:28953949

Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis.

PubMed

Shin, Hye Won; Ju, Bum Jun; Jang, Yoo Kyung; You, Hae Seun; Kang, Hyun; Park, Ji Yong

2017-01-01

Tramadol, a 4-phenyl-piperidine analog of codeine, has a unique action in that it has a central opioidergic, noradrenergic, serotonergic analgesic, and peripheral local anesthetic (LA) effect. Many studies have reported contradictory findings regarding the peripheral analgesic effect of tramadol as an adjuvant to LA in brachial plexus block (BPB). This meta-analysis aimed to evaluate the effects of tramadol as an adjunct to LA in BPB during shoulder or upper extremity surgery. We searched the PubMed, EMBASE, Cochrane, KoreaMed databases, and Google Scholar for eligible randomized controlled trials (RCTs) that compared BPB with LA alone and BPB with LA and tramadol. Primary outcomes were the effects of tramadol as an adjuvant on duration of sensory block, motor block, and analgesia. Secondary outcomes were the effects of tramadol as an adjuvant on time to onset of sensory block and motor block and on adverse effects. We performed the meta-analysis using Review Manager 5.3 software. We identified 16 RCTs with 751 patients. BPB with tramadol prolonged the duration of sensory block (mean difference [MD], -61.5 min; 95% CI, -95.5 to -27.6; P = 0.0004), motor block (MD, -65.6 min; 95% CI, -101.5 to -29.7; P = 0.0003), and analgesia (MD, -125.5 min; 95% CI, -175.8 to -75.3; P < 0.0001) compared with BPB without tramadol. Tramadol also shortened the time to onset of sensory block (MD, 2.1 min; 95% CI, 1.1 to 3.1; P < 0.0001) and motor block (MD, 1.2 min; 95% CI, 0.2 to 2.1; P = 0.010). In subgroup analysis, the duration of sensory block, motor block, and analgesia was prolonged for BPB with tramadol 100 mg (P < 0.05) but not for BPB with tramadol 50 mg. The quality of evidence was high for duration of analgesia according to the GRADE system. Adverse effects were comparable between the studies. In upper extremity surgery performed under BPB, use of tramadol 100 mg as an adjuvant to LA appears to prolong the duration of sensory block, motor block, and analgesia, and shorten the time to onset of sensory and motor blocks without altering adverse effects.

Effectiveness of SmartGuard Technology in the Prevention of Nocturnal Hypoglycemia After Prolonged Physical Activity.

PubMed

Petruzelkova, Lenka; Pickova, Klara; Sumnik, Zdenek; Soupal, Jan; Obermannova, Barbora

2017-05-01

The prevention of postexercise nocturnal hypoglycemia after prolonged physical activity using sensor-augmented pump (SAP) therapy with predictive low-glucose management (PLGM) has not been well studied. We conducted a study at a pediatric diabetes camp to determine whether a SAP with PLGM reduces the frequency of nocturnal hypoglycemia after prolonged physical activity more effectively than a SAP with a carbohydrate intake algorithm. During a 1-week sport camp, 20 children (aged 10-13 years) with type 1 diabetes (T1D) managed by SAP therapy either with (n = 7) or without PLGM (n = 13) were studied. The hypoglycemia management strategy and the continuous glucose monitoring (CGM)/PLGM settings were standardized. The incidence, severity, and duration of hypoglycemia and carbohydrate intake were documented and compared. The PLGM system was activated on 78% of all nights (once per night on average). No difference was found between the SAP and PLGM groups in the mean overnight glucose curve or mean morning glucose (7.8 ± 2 mmol/L vs. 7.4 ± 3 mmol/L). There was no difference in the frequency and severity of hypoglycemia. However, the SAP group consumed significantly more carbohydrates to prevent and treat hypoglycemia than those in the PLGM group; the values were 10 ± 2 and 1 ± 2 gS (P < 0.0001) in the SAP and PLGM groups, respectively. Moreover, the SAP group spent a significantly longer time in hypoglycemia (64 ± 2 min vs. 38 ± 2 min, P < 0.05). We observed a difference in the time distribution of nocturnal hypoglycemia (10 to 12 p.m. in the PLGM group and 3 to 7 a.m. in the SAP group, P < 0.05). With PLGM system, euglycemia after prolonged physical activity was largely maintained with a minimal carbohydrate intake.

Effect of switching off unidirectional downflow systems of operating theaters during prolonged inactivity on the period before the operating theater can safely be used.

PubMed

Traversari, A A L; Bottenheft, C; van Heumen, S P M; Goedhart, C A; Vos, M C

2017-02-01

Switching off air handling systems in operating theaters during periods of prolonged inactivity (eg, nights, weekends) can produce a substantial reduction of energy expenditure. However, little evidence is available regarding the effect of switching off the air handling system during periods of prolonged inactivity on the air quality in operating theaters during operational periods. The aim of this study is to determine the amount of time needed after restarting the ventilation system to return to a stable situation, with air quality at least equal to the situation before switching off the system. Measurements were performed in 3 operating theaters, all of them equipped with a unidirectional downflow (UDF) system. Measurements (particle counts of emitted particles with a particle size ≥0.5 µm) were taken during the start-up of the ventilation system to determine when prespecified degrees of protection were achieved. Temperature readings were taken to determine when a stable temperature difference between the periphery and the protected area was reached, signifying achievement of a stable condition. After starting up the system, the protected area achieved the required degrees of protection within 20 minutes (95% upper confidence limit). A stable temperature difference was achieved within 23 minutes (95% upper confidence limit). Both findings lie well within the period of 25 minutes normally required for preparations before the start of surgical procedures. Switching off the ventilation system during prolonged inactivity (during the night and weekend) has no negative effect on the air quality in UDF operating theaters during normal operational hours. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Combined antiallodynic effect of Neurotropin® and pregabalin in rats with L5-spinal nerve ligation.

PubMed

Okazaki, Ryohei; Namba, Hiroyoshi; Yoshida, Hiroyuki; Okai, Hisashi; Taguchi, Kazuki; Kawamura, Minoru

2013-03-12

In this study, we investigated the combined effect of Neurotropin® and pregabalin for L5-spinal nerve ligation (L5-SNL) model in rats and thiopental-induced sleep in mice. The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. The hindpaw withdrawal threshold was measured by application of von Frey filaments. Thiopental sodium was intravenously administered in mice and sleeping time was measured. In L5-SNL rats, an isobolographic analysis was performed to clarify the combined antiallodynic effect of Neurotropin and pregabalin 14 days after ligation in rats. In isobolographic analysis and thiopental-induced sleep test, Neurotropin and pregabalin were orally administered to coincide with the timing of the peak effect of each drug. Neurotropin (50-200 NU/kg) and pregabalin (2.5-10mg/kg) showed a dose-dependent antiallodynic action in L5-SNL rats. The antiallodynic effect of pregabalin was reversed by intrathecal injection of yohimbine or ondansetron. Isobolographic analysis suggested that the combined antiallodynic effect of Neurotropin and pregabalin in L5-SNL rats may have been more than a mere additive effect. Neurotropin (50-400 NU/kg) had no effect on thiopental-induced sleeping time whereas pregabalin (30-100mg/kg) significantly prolonged it. When the dose of pregabalin was 30 mg/kg, Neurotropin (50-400 NU/kg) did not further exacerbate the prolongation effect of pregabalin on thiopental-induced sleep. It was suggested that when Neurotropin was administered in combination with pregabalin, it might provide more effective pain relief than that obtained with each agent alone in neuropathic pain without aggravating adverse effects of pregabalin. Copyright © 2013 Elsevier Inc. All rights reserved.

Regular moist snuff dipping does not affect endurance exercise performance.

PubMed

Björkman, Frida; Edin, Fredrik; Mattsson, C Mikael; Larsen, Filip; Ekblom, Björn

2017-01-01

Physiological and medical effects of snuff have previously been obtained either in cross-sectional studies or after snuff administration to non-tobacco users. The effects of snuff cessation after several years of daily use are unknown. 24 participants with >2 years of daily snuff-use were tested before and after >6 weeks snuff cessation (SCG). A control group (CO) of 11 snuff users kept their normal habits. Resting heart rate (HR) and blood pressure (BP) were significantly lower in SCG after snuff cessation, and body mass was increased by 1.4 ± 1.7 kg. Total cholesterol increased from 4.12 ± 0.54 (95% CI 3.89-4.35) to 4.46 ± 0.70 (95% CI 4.16-4.75) mM L-1 in SCG, due to increased LDL, and this change was significantly different from CO. Resting values of HDL, C-reactive protein, and free fatty acids (FFA) remained unchanged in both groups. In SCG group, both HR and BP were reduced during a four-stage incremental cycling test (from 50 to 80% of VO2max) and a prolonged cycling test (60 min at 50% of VO2max). Oxygen uptake (VO2), respiratory exchange ratio, blood lactate (bLa) and blood glucose (bGlu) concentration, and rate of perceived exertion (RPE) were unchanged. In CO group, all measurements were unchanged. During the prolonged cycling test, FFA was reduced, but with no significant difference between groups. During the maximal treadmill running test peak values of VO2, pulmonary ventilation (VE), time to exhaustion and bLa were unchanged in both groups. In conclusion, endurance exercise performance (VO2max and maximal endurance time) does not seem to be affected by prolonged snuff use, while effects on cardiovascular risk factors are contradictory. HR and BP during rest and submaximal exercise are reduced after cessation of regular use of snuff. Evidently, the long-time adrenergic stress on circulation is reversible.

Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

NASA Technical Reports Server (NTRS)

Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

1998-01-01

Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

The World Health Organisation. The regions--too much power, too little effect.

PubMed Central

Godlee, F.

1994-01-01

WHO's regional offices make it structurally one of the most decentralised of all United Nations agencies. But at what cost and to what effect? This article argues that too often the regions give only the illusion of decentralisation while wresting power from WHO's governing body and prolonging the time taken for resources to reach the point of need. Images p1569-a p1569-b PMID:7819902

Purification and characterization of a heteromultimeric glycoprotein from Artocarpus heterophyllus latex with an inhibitory effect on human blood coagulation.

PubMed

Siritapetawee, Jaruwan; Thammasirirak, Sompong

2011-01-01

Plant latex has many health benefits and has been used in folk medicine. In this study, the biological effect of Artocarpus heterophyllus (jackfruit) latex on human blood coagulation was investigated. By a combination of heat precipitation and ion-exchange chromatography, a heat stable heteromultimeric glycoprotein (HSGPL1) was purified from jackfruit milky latex. The apparent molecular masses of the monomeric proteins on SDS/PAGE were 33, 31 and 29 kDa. The isoelectric points (pIs) of the monomers were 6.63, 6.63 and 6.93, respectively. Glycosylation and deglycosylation tests confirmed that each subunit of HSGPL1 formed the native multimer by sugar-based interaction. Moreover, the multimer of HSGPL1 also resisted 2-mercaptoethanol action. Peptide mass fingerprint analysis indicated that HSGPL1 was a complex protein related to Hsps/chaperones. HSGPL1 has an effect on intrinsic pathways of the human blood coagulation system by significantly prolonging the activated partial thrombin time (APTT). In contrast, it has no effect on the human extrinsic blood coagulation system using the prothrombin time (PT) test. The prolonged APTT resulted from the serine protease inhibitor property of HSGPL1, since it reduced activity of human blood coagulation factors XI(a) and α-XII(a).

Long-term bioavailability of redox nanoparticles effectively reduces organ dysfunctions and death in whole-body irradiated mice.

PubMed

Feliciano, Chitho P; Tsuboi, Koji; Suzuki, Kenshi; Kimura, Hiroyuki; Nagasaki, Yukio

2017-06-01

Radioprotective agents have been developed to protect patients against the damaging and lethal effects of ionizing radiation. However, in addition to the intrinsic ability to target reactive oxygen species (ROS), the ability to retain a significant level of bioavailability is desirable in radioprotective agents because that would increase and prolong their radioprotective efficacy and improve its safety. Here, we report the development of a novel nanoparticle-based radioprotective agent with improved bioavailability, which suppressed the adverse effects typically associated with low-molecular-weight (LMW) antioxidants. We developed biocompatible and colloidally stable nanoparticles in which nitroxide radicals that were covalently conjugated (redox nanoparticles, RNP N ) effectively scavenged radiation-induced ROS with a characteristically prolonged bioavailability and tissue-residence time compared with that of conventional LMW antioxidants. The confinement of the nitroxide radicals in the RNP N core prevented its rapid metabolism and excretion out of the body. The nano-sized formulation prevented internalization of RNP N in healthy cells, thereby preserving the normal function of the redox reactions in the cell. This improved pharmacological performance dramatically reduced the radiation-induced organ dysfunctions and increased the survival time of the lethally irradiated mice when the nanoparticles were administered 3-24 h before whole-body irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of prolonged violent video-gaming on adolescent sleep: an experimental study.

PubMed

King, Daniel L; Gradisar, Michael; Drummond, Aaron; Lovato, Nicole; Wessel, Jason; Micic, Gorica; Douglas, Paul; Delfabbro, Paul

2013-04-01

Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep. © 2012 European Sleep Research Society.

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

PubMed

Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

2016-07-01

Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart.

PubMed

Klein, Michael G; Shou, Matie; Stohlman, Jayna; Solhjoo, Soroosh; Haigney, Myles; Tidwell, Richard R; Goldstein, Robert E; Flagg, Thomas P; Haigney, Mark C

2017-08-01

The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes (P < .001) and 26.2% in HF wedges (P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart. Published by Elsevier Inc.

Population Pharmacokinetic-Pharmacodynamic Analysis to Compare the Effect of Moxifloxacin on QT Interval Prolongation Between Healthy Korean and Japanese Subjects.

PubMed

Choi, Hyang-Ki; Jung, Jin Ah; Fujita, Tomoe; Amano, Hideki; Ghim, Jong-Lyul; Lee, Dong-Hwan; Tabata, Kenichi; Song, Il-Dae; Maeda, Mika; Kumagai, Yuji; Mendzelevski, Boaz; Shin, Jae-Gook

2016-12-01

The goal of this study was to evaluate the moxifloxacin-induced QT interval prolongation in healthy male and female Korean and Japanese volunteers to investigate interethnic differences. This multicenter, randomized, double-blind, placebo-controlled, 2-way crossover study was conducted in healthy male and female Korean and Japanese volunteers. In each period, a single dose of moxifloxacin or placebo 400 mg was administered orally under fasting conditions. Triplicate 12-lead ECGs were recorded at defined time points before, up to 24 hours after dosing, and at corresponding time points during baseline. Serial blood sampling was conducted for pharmacokinetic analysis of moxifloxacin. The pharmacokinetic-pharmacodynamic data between the 2 ethnic groups were compared by using a typical analysis based on the intersection-union test and a nonlinear mixed effects method. A total of 39 healthy subjects (Korean, male: 10, female: 10; Japanese, male: 10, female: 9) were included in the analysis. The concentration-effect analysis revealed that there was no change in slope (and confirmed that the difference was caused by a change in the pharmacokinetic model of moxifloxacin). A 2-compartment model with first-order absorption provided the best description of moxifloxacin's pharmacokinetic parameters. Weight and sex were selected as significant covariates for central volume of distribution and intercompartmental clearance, respectively. An E max model (E[C]=[E max ⋅C]/[EC 50 +C]) described the QT interval data of this study well. However, ethnicity was not found to be a significant factor in a pharmacokinetic-pharmacodynamic link model. The drug-induced QTc prolongations evaluated using moxifloxacin as the probe did not seem to be significantly different between these Korean and Japanese subjects. ClinicalTrials.gov identifier: NCT01876316. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Dissociation between the pharmacokinetics and pharmacodynamics of once-daily rivaroxaban and twice-daily apixaban: a randomized crossover study.

PubMed

Kreutz, R; Persson, P B; Kubitza, D; Thelen, K; Heitmeier, S; Schwers, S; Becka, M; Hemmrich, M

2017-10-01

Essentials In this crossover study the anticoagulant effects of rivaroxaban and apixaban were compared. Healthy volunteers received rivaroxaban 20 mg once daily or apixaban 5 mg twice daily. Rivaroxaban was associated with more prolonged inhibition of thrombin generation than apixaban. Rivaroxaban induced a clear prolongation of prothrombin time and activated partial thromboplastin time. Background The anticoagulant actions of the oral direct activated factor Xa inhibitors, rivaroxaban and apixaban, have not previously been directly compared. Objectives To compare directly the steady-state pharmacokinetics and anticoagulant effects of rivaroxaban and apixaban at doses approved for stroke prevention in patients with non-valvular atrial fibrillation. Methods Twenty-four healthy Caucasian male volunteers were included in this open-label, two-period crossover, phase 1 study (EudraCT number: 2015-002612-32). Volunteers were randomized to receive rivaroxaban 20 mg once daily or apixaban 5 mg twice daily for 7 days, followed by a washout period of at least 7 days before they received the other treatment. Plasma concentrations and anticoagulant effects were measured at steady state and after drug discontinuation. Results Overall exposure was similar for both drugs: the geometric mean area under the plasma concentration-time curve for the 0-24-h interval was 1830 μg h L -1 for rivaroxaban and 1860 μg h L -1 for apixaban. Rivaroxaban was associated with greater inhibition of endogenous thrombin potential (geometric mean area under the curve relative to baseline during the 0-24-h interval: 15.5 h versus 17.5 h) and a more pronounced maximal prolongation relative to baseline of prothrombin time (PT) (1.66-fold versus 1.14-fold) and activated partial thromboplastin time (APTT) (1.43-fold versus 1.16-fold) at steady state than apixaban. Conclusions Despite similar exposure to both drugs, rivaroxaban 20 mg once daily was associated with greater and more sustained inhibition of thrombin generation than apixaban 5 mg twice daily. Sensitive PT and APTT assays can be used to estimate the anticoagulant effects of rivaroxaban. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Defining the association between operative time and outcomes in children's surgery.

PubMed

Short, Heather L; Fevrier, Helene B; Meisel, Jonathan A; Santore, Matthew T; Heiss, Kurt F; Wulkan, Mark L; Raval, Mehul V

2017-10-01

Prolonged operative time (OT) is considered a reflection of procedural complexity and may be associated with poor outcomes. Our purpose was to explore the association between prolonged OT and complications in children's surgery. 182,857 cases from the 2012-2014 NSQIP-Pediatric were organized into 33 groups. OT for each group was analyzed by quartile, and regression models were used to determine the relationship between prolonged OT and complications. Variations in OT existed for both short and long procedures. Cases in the longest quartile had twice the odds of postoperative complications after adjusting for age, sex and BMI (OR 1.85; 95% CI 1.78-1.91). Procedure-specific prolonged OT was associated with postoperative complications for the majority (85%) of procedural groupings. Prolonged OT was associated with minor complications in gynecologic (OR 4.17; 95% CI 2.19-7.96), urologic (OR 2.88; 95% CI 2.40-3.44), and appendix procedures (OR 2.88; 95% CI 2.49-3.34). There were increased odds of major complications in foregut (OR 6.56; 95% CI 4.99-8.64), gynecologic (OR 3.07; 95% CI 1.84-5.13), and spine procedures (OR 2.99; 95% CI 2.57-3.28). Prolonged OT is associated with increased odds of postoperative complications across a spectrum of children's surgical procedures. Factors contributing to prolonged OT merit further investigation and may serve as a target for future quality improvement. Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimism in prolonged grief and depression following loss: A three-wave longitudinal study.

PubMed

Boelen, Paul A

2015-06-30

There is considerable evidence that optimism, the predisposition to have generalized favorable expectancies for the future, is associated with numerous desirable outcomes. Few studies have examined the association of optimism with emotional distress following the death of a loved one. Doing so is important, because optimism may be an important target for interventions for post-loss psychopathology. In the current study, we examined the degree to which optimism, assessed in the first year post-loss (Time 1, T1), was associated with symptom levels of prolonged grief and depression six months (Time 2, T2) and fifteen months (Time 3, T3) later, controlling for baseline symptoms and also taking into account positive automatic cognitions at T1. Findings showed that higher optimism at T1 was associated with lower concurrent prolonged grief and depression severity. Higher optimism at T1 was also inversely related with depression symptom severity at T2 and T3, but not prolonged grief severity at T2 and T3. Implications of these findings are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A pharmacokinetic-pharmacodynamic model for the quantitative prediction of dofetilide clinical QT prolongation from human ether-a-go-go-related gene current inhibition data.

PubMed

Jonker, Daniël M; Kenna, Leslie A; Leishman, Derek; Wallis, Rob; Milligan, Peter A; Jonsson, E Niclas

2005-06-01

QT prolongation is an important biomarker of the arrhythmia torsades de pointes and appears to be related mainly to blockade of delayed inward cardiac rectifier potassium currents. The aim of this study was to quantify the relationship between in vitro human ether-a-go-go-related gene (hERG) potassium channel blockade and the magnitude of QT prolongation in humans for the class III antiarrhythmic dofetilide. The in vitro affinity and activity of dofetilide were determined in recombinant cell cultures expressing the hERG channel, and the QT-prolonging effect of dofetilide was assessed in 5 clinical studies (80 healthy volunteers and 17 patients with ischemic heart disease). A population pharmacokinetic-pharmacodynamic analysis of the in vitro and in vivo data was performed in NONMEM by use of the operational model of pharmacologic agonism to estimate the efficiency of transduction from ion channel binding to Fridericia-corrected QT response. A 3-compartment pharmacokinetic model with first-order absorption characterized the time course of dofetilide concentrations. On the basis of an in vitro potency of 5.13 ng/mL for potassium current inhibition and predicted unbound dofetilide concentrations, the estimated transducer ratio (tau) of 6.2 suggests that the QT response plateaus before currents are fully blocked. In our study population, 10% hERG blockade corresponds to a QT prolongation of 20 ms (95% confidence interval, 12-32 ms). With long-term dofetilide administration, tolerance develops with a half-life of 4.7 days. The current mechanism-based pharmacokinetic-pharmacodynamic model quantified the relationship between in vitro hERG channel blockade and clinical QT prolongation for dofetilide. This model may prove valuable for assessing the risk of QT prolongation in humans for other drugs that selectively block the hERG channel on the basis of in vitro assays and pharmacokinetic properties.

Central effect of taurine and its analogues on fever caused by intravenous leukocytic pyrogen in the rabbit.

PubMed Central

Lipton, J M; Ticknor, C B

1979-01-01

1. Taurine infused I.C.V. after I.V. injection of leukocytic pyrogen (LP) inhibited the initial rise in body temperature and prolonged fever when infusion was stopped. 2. Similar infusion of taurine also inhibited the hypertermic effect of I.C.V. PGE2 (0.5 microgram) but did not cause prolonged hyperthermia. 3. I.C.V. administration of the taurine analogues hypotaurine and beta-alanine, compounds which have been shown previously to compete with taurine for facilitated transport in C.N.S. tissue, also inhibited the initial increase in body temperature and prolonged LP fever. 4. These results suggest that taurine prolongs LP fever by preferentially occupying a carrier system normally required for termination of the effects of endogenous pyrogens or related central mediators of fever. There was no evidence that taurine prolongs fever by blocking inactivation of central PGE2, a substance proposed previously to be a central mediator of fever. PMID:107309

Changes in CR-39 proton sensitivity due to prolonged exposure to high vacuums relevant to the National Ignition Facility and OMEGA.

PubMed

Manuel, M J-E; Rosenberg, M J; Sinenian, N; Rinderknecht, H; Zylstra, A B; Séguin, F H; Frenje, J; Li, C K; Petrasso, R D

2011-09-01

When used at facilities like OMEGA and the NIF, CR-39 is exposed to high vacuum environments before and after irradiation by charged particles and neutrons. Using an electrostatic linear accelerator at MIT, studies have been conducted to investigate the effects of high vacuum exposure on the sensitivity of CR-39 to fusion protons in the ~1-9 MeV energy range. High vacuum conditions, of order 10(-5) Torr, experienced by CR-39 samples at these facilities were emulated. It is shown that vacuum exposure times longer than ~16 h before proton irradiation result in a decrease in proton sensitivity, whereas no effect was observed for up to 67 h of vacuum exposure after proton irradiation. CR-39 sensitivity curves are presented for samples with prolonged exposure to high vacuum before and after proton irradiation. © 2011 American Institute of Physics

Effects of prolonged physical exercise and fasting upon plasma testosterone level in rats.

PubMed

Guezennec, C Y; Ferre, P; Serrurier, B; Merino, D; Pesquies, P C

1982-01-01

Prolonged physical exercise and fasting in male rats were studied to determine the effect of these two treatments on plasma testosterone level. Blood and tissue samples were drawn after 1 h, 3 h, 5 h, and 7 h treadmill running, and after 24 h, 48 h, and 72 h of fasting. Both treatments resulted in a significant fall in plasma testosterone, plasma luteinizing hormone (LH), plasma Insulin (IRI) and in liver and muscle glycogen stores. In the course of these two treatments the injection of a supra maximal dose of Human Chorionic Gonadotropin (HCG) produced a rise in plasma testosterone similar to that in control rats. This indicates that the decrease of plasma LH may be responsible for the decrease in plasma testosterone, which is time-related with the decrease in glycogen stores. The possible metabolic role of the decrease in plasma testosterone is discussed.

Prolonging the duration of masseter muscle reduction by adjusting the masticatory movements after the treatment of masseter muscle hypertrophy with botulinum toxin type a injection.

PubMed

Wei, Jiao; Xu, Hua; Dong, Jiasheng; Li, Qingfeng; Dai, Chuanchang

2015-01-01

Botulinum toxin type A (BTX-A) is widely used for the clinical treatment of masseteric hypertrophy. Until now, few reports have discussed how to prolong the duration of its effectiveness. This study evaluated that purposely adjusting the masticatory movements is possible of postponing the masseter muscle rehypertrophy. Ninety-eight patients were randomly and equally divided into 2 groups, and 35 U BTX-A per side was injected into the masseters. The thickness and volume of the masticatory muscles were measured by ultrasound and computerized tomography, respectively. Patients in Group 1 were instructed to strengthen their masticatory effort during the denervated atrophic stage of the masseter (the interval was evaluated by real-time ultrasound monitoring), whereas patients in Group 2 were not given this instruction. When the masseter muscle began to recover, patients in both groups were instructed to reduce their chewing. The duration of the masseter muscle rehypertrophy was significantly prolonged in Group 1 patients. The thickness and the volume of the other masticatory muscles were significantly increased in Group 1 but were either slightly decreased or insignificantly different in Group 2. Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.

TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets

PubMed Central

Xia, Luxi; Bartlett, Donald; Leiter, J.C.

2011-01-01

Elevating body temperature or just the temperature of the dorsal medulla by approximately 2 °C prolongs the laryngeal chemoreflex (LCR) in decerebrate neonatal piglets. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) receptors in the nucleus of the solitary tract (NTS) mediate thermal prolongation of the LCR. We studied the effect of a selective TRPV1 receptor antagonist on thermal prolongation of the LCR, and we tested the effect of a TRPV1 agonist on the duration of the LCR under normothermic conditions. We studied 37 decerebrate neonatal piglets between the ages of post-natal days 4 and 7. The TRPV1 receptor antagonist, 5−iodoresiniferatoxin (65 microM/L in 100 nL), blocked thermal prolongation of the LCR when injected bilaterally into the region of the NTS. The TRPV1 agonist, resiniferatoxin (0.65-1.0 mM/L in 100 nL), prolonged the LCR after bilateral injection into the NTS even when the body temperature of each piglet was normal. The effect of the TRPV1 agonists could be blocked by treatment with the GABAA receptor antagonist, bicuculline, whether given intravenously (0.3 mg/kg) or focally injected bilaterally into the NTS (10 mM in 100nL). We conclude that TRPV1 receptors in the NTS mediate thermal prolongation of the LCR. PMID:21276877

The biological effect of prolonged radiation and ways of selecting new anti-radiation drugs effective in this kind of radiation injury

NASA Technical Reports Server (NTRS)

Rogozkin, V. D.; Chertkov, K. S.; Nikolov, I.

1974-01-01

The basic characteristics of prolonged radiation - increased tolerance of radiation injury - are attributed to cellular kinetics; as dose rate is reduced, the population rate is not disturbed, particularly that of stem cells which makes it possible for the organism to tolerate higher radiation loads. It is concluded that this effect makes approved radio protectors, whose effect contains an established cytostatic component, unsuitable for prolonged radiation. It is better to correct the stem pool formation process by either accelerating the proliferation of cells or limiting the effect of stimuli causing cells to lose colony forming properties.

Postantifungal effect of the combination of caspofungin with voriconazole and amphotericin B against clinical Candida krusei isolates.

PubMed

Oz, Yasemin; Kiremitci, Abdurrahman; Dag, Ilknur; Metintas, Selma; Kiraz, Nuri

2013-01-01

We evaluated the postantifungal effects (PAFEs) of caspofungin (CAS), voriconazole (VOR), amphotericin B (AmB), and the combinations of CAS + VOR and CAS + AmB against 30 clinical Candida krusei isolates at 0.25, 1 and 4 times the MIC of each individually and in the indicated combinations. Antifungals were removed after 1 hour and colony counts were performed at 0, 2, 6, 24, and 48 h. VOR did not display any measurable PAFE regardless of antifungal concentrations, while AmB and CAS exhibited dose-dependent PAFE. The most effective agent producing a prolonged PAFE in this study was CAS. Although the combination of CAS with VOR generated longer PAFEs at 0.25 and 1 times their respective MICs in comparison with CAS alone, this combination was indifferent rather than synergistic. However, the combination of CAS with AmB at 4 times their MICs exhibited the best performance, reducing the colony counts during the 48 h after removal of drugs and resulted in synergic interaction in respect to 20 (67%) isolates. Consequently, CAS has a prolonged PAFE in vitro against C. krusei isolates, and the combination of AmB + CAS may increase significantly the efficacy of CAS. Our data may be useful in optimizing dosing regimens for these agents and their combinations, although further studies are needed to explore the clinical usefulness of our results.

EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2007-01-01

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

PubMed

Strauss, David G; Vicente, Jose; Johannesen, Lars; Blinova, Ksenia; Mason, Jay W; Weeke, Peter; Behr, Elijah R; Roden, Dan M; Woosley, Ray; Kosova, Gulum; Rosenberg, Michael A; Newton-Cheh, Christopher

2017-04-04

Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Genetic analysis of 22 subjects was performed in a secondary analysis of a randomized, double-blind, placebo-controlled, crossover trial of 3 QT-prolonging drugs with 15 time-matched QT and plasma drug concentration measurements. Subjects received single doses of dofetilide, quinidine, ranolazine, and placebo. The outcome was the correlation between a genetic QT score comprising 61 common genetic variants and the slope of an individual subject's drug-induced increase in heart rate-corrected QT (QTc) versus drug concentration. The genetic QT score was correlated with drug-induced QTc prolongation. Among white subjects, genetic QT score explained 30% of the variability in response to dofetilide ( r =0.55; 95% confidence interval, 0.09-0.81; P =0.02), 23% in response to quinidine ( r =0.48; 95% confidence interval, -0.03 to 0.79; P =0.06), and 27% in response to ranolazine ( r =0.52; 95% confidence interval, 0.05-0.80; P =0.03). Furthermore, the genetic QT score was a significant predictor of drug-induced torsade de pointes in an independent sample of 216 cases compared with 771 controls ( r 2 =12%, P =1×10 -7 ). We demonstrate that a genetic QT score comprising 61 common genetic variants explains a significant proportion of the variability in drug-induced QT prolongation and is a significant predictor of drug-induced torsade de pointes. These findings highlight an opportunity for recent genetic discoveries to improve individualized risk-benefit assessment for pharmacological therapies. Replication of these findings in larger samples is needed to more precisely estimate variance explained and to establish the individual variants that drive these effects. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01873950. © 2017 American Heart Association, Inc.

Effects of Ultrasound Assistance on Dehydration Processes and Bioactive Component Retention of Osmo-Dried Sour Cherries.

PubMed

Siucińska, Karolina; Mieszczakowska-Frąc, Monika; Połubok, Aleksandra; Konopacka, Dorota

2016-07-01

Despite having numerous health benefits, dried sour cherries have proven to be more acceptable to consumers when infused with sugar or other sweeteners to enhance their flavor, which, in turn, leads to serious anthocyanin losses. For this reason, a consideration was made for the application of ultrasound to accelerate solid gain and shorten drying time, thus favoring bioactive component retention. To determine the usefulness of ultrasound as a tool for sour cherry osmotic infusion enhancement, the effect of sonication time on dehydration effectiveness, as well as the stability of bioactive components during osmotic treatment and consecutive convective drying, was investigated. Fruits were osmo-dehydrated using a 60% sucrose solution for 120 min (40 °C), during which, ultrasound of 25 kHz (0.4 W/cm(2) ), was applied for 0, 30, 60, 90, and 120 min, after which, the fruits were convectively dried. In the range of the applied ultrasound energy no significant effect of sonication on mass transfer intensification was observed; moreover, longer acoustic treatment seemed to retard moisture removal during subsequent convective drying, which can be related to the breakdown of the parenchyma cell walls caused by the prolonged ultrasound (US) action. It was concluded that although US assistance could be considered neutral for bioactive component retention, excessive sonication time can lead to some anthocyanin deterioration. According to high-performance liquid chromatography analysis, the particular anthocyanin alterations, both during dehydration and final drying, occurred in a similar way. Sonication time prolongation caused approximately 10% more bioactive compound deterioration, than earlier, shorter trials. © 2016 Institute of Food Technologists®

Crowding of Drosophila larvae affects lifespan and other life-history traits via reduced availability of dietary yeast.

PubMed

Klepsatel, Peter; Procházka, Emanuel; Gáliková, Martina

2018-06-19

Conditions experienced during development have often long-lasting effects persisting into adulthood. In Drosophila, it is well-documented that larval crowding influences fitness-related traits such as body size, starvation resistance and lifespan. However, the underlying mechanism of this phenomenon is not well understood. Here, we show that the effects of increased larval density on life-history traits can be explained by decreased yeast availability in the diet during development. Yeast-poor larval diet alters various life-history traits and mimics the effects of larval crowding. In particular, reduced amount of yeast in larval diet prolongs developmental time, reduces body size, increases body fat content and starvation resistance, and prolongs Drosophila lifespan. Conversely, the effects of larval crowding can be rescued by increasing the concentration of the dietary yeast in the diet during development. Altogether, our results show that the well-known effects of larval crowding on life-history traits are mainly caused by the reduced availability of dietary yeasts due to increased larval competition. Copyright © 2018. Published by Elsevier Inc.

The Effect of Lateral Ankle Ligament Repair in Muscle Reaction Time in Patients with Mechanical Ankle Instability.

PubMed

Li, H-Y; Zheng, J-J; Zhang, J; Hua, Y-H; Chen, S-Y

2015-11-01

Studies have shown that functional ankle instability can result in prolonged muscle reaction time. However, the deficit in muscle reaction time in patients with mechanical ankle instability (MAI) and the effect of lateral ankle ligament repair on muscle reaction time are unclear. The purpose of this study was to identify the deficit in muscle reaction time, and to evaluate the role of lateral ligament repair in improving muscle reaction time in MAI patients. Sixteen MAI patients diagnosed with lateral ankle ligament tears by ultrasonography and magnetic resonance imaging underwent arthroscopic debridement and open lateral ankle ligament repair with a modified Broström procedure. One day before the operation, reaction times of the tibialis anterior and peroneus longus muscles were recorded following sudden inversion perturbation while walking on a custom walkway, and anterior drawer test (ADT) and American Orthopaedic Foot and Ankle Society (AOFAS) scale score were evaluated. Six months postoperatively, muscle reaction time, ADT and AOFAS scale score were reevaluated, and muscle reaction times in 15 healthy controls were also recorded. Preoperatively, the affected ankles in the MAI group had significantly delayed tibialis anterior and peroneus longus muscles reaction times compared with controls. Six months after the operation, median AOFAS scale scores were significantly greater than preoperatively, and ADT was negative in the MAI group. However, the affected ankles in the MAI group showed no difference in muscle reaction time compared with preoperative values. MAI patients had prolonged muscle reaction time. The modified Broström procedure produced satisfactory clinical outcomes in MAI patients, but did not shorten reaction times of the tibialis anterior and peroneus longus muscles. © Georg Thieme Verlag KG Stuttgart · New York.

Prolonged tomato juice consumption has no effect on cell-mediated immunity of well-nourished elderly men and women.

PubMed

Watzl, B; Bub, A; Blockhaus, M; Herbert, B M; Lührmann, P M; Neuhäuser-Berthold, M; Rechkemmer, G

2000-07-01

The immunomodulatory potential of carotenoids has been investigated thoroughly only for beta-carotene. Data on the immunomodulatory activity of other carotenoids such as lycopene are scarce. The objective of this study was to investigate the effects of prolonged tomato juice consumption on cell-mediated immunity of well-nourished healthy elderly persons. In an intervention study, 33 female and 20 male subjects (aged 63-86 y) consumed 330 mL/d tomato juice (47.1 mg/d lycopene) or mineral water for 8 wk. Immune status was assessed by measuring number and lytic activity of natural killer (NK) cells, secretion of cytokines [interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha)] by activated peripheral blood mononuclear cells (PBMC), lymphocyte proliferation, and delayed-type hypersensitivity (DTH) skin responses. Tomato juice consumption resulted in significantly increased plasma lycopene and beta-carotene concentrations over time. In both treatment groups, TNF-alpha and IL-4 secretion were increased at the end of the intervention period, whereas IL-2 secretion was decreased. Tomato juice consumption had no effect on lymphocyte proliferation, DTH or the number of NK cells. Lytic activity of NK cells was increased in both groups at the end of the intervention period. In conclusion, these results show that prolonged tomato juice consumption increased plasma lycopene concentrations without significantly affecting cell-mediated immunity in well-nourished elderly subjects.

Erythrocyte membrane alterations as the basis of chlorate toxicity.

PubMed

Singelmann, E; Wetzel, E; Adler, G; Steffen, C

1984-03-01

The effects of sodium chlorate and of sodium nitrite on human erythrocytes were studied in vitro. Nitrite rapidly oxidised haemoglobin and glutathione; reduction of methaemoglobin (Hbi) by methylene blue was complete during 3 h of incubation with nitrite. With chlorate, a concentration-dependent lag phase was seen before Hbi was formed. After prolonged incubation, Hbi could no longer be reduced with methylene blue. Several other effects were observed that explain the clinical picture of chlorate poisoning which involves haemolysis followed by disseminated intravascular coagulation and renal failure: increased permeability to cations, increased resistance to hypotonic haemolysis and prolonged filtration time through polycarbonate membranes with cylindrical pores of 5 micron diameter. This suggests an increased membrane rigidity due to membrane protein polymerisation, as demonstrated by SDS polyacrylamide gel electrophoresis. Simultaneously, erythrocyte enzymes were inactivated, primarily glucose-6-phosphate dehydrogenase which is necessary for the therapeutic effect of methylene blue. This explains the inefficacy of methylene blue in the treatment of a case of chlorate poisoning that we observed (Arch. Toxicol., 48 (1981) 281).

P38 Mitogen-activated Protein Kinase Activity Is Required during Mitosis for Timely Satisfaction of the Mitotic Checkpoint But Not for the Fidelity of Chromosome Segregation

PubMed Central

Lee, Kyunghee; Kenny, Alison E.

2010-01-01

Although p38 activity is reported to be required as cells enter mitosis for proper spindle assembly and checkpoint function, its role during the division process remains controversial in lieu of direct data. We therefore conducted live cell studies to determine the effect on mitosis of inhibiting or depleting p38. We found that in the absence of p38 activity the duration of mitosis is prolonged by ∼40% in nontransformed human RPE-1, ∼80% in PtK2 (rat kangaroo), and ∼25% in mouse cells, and this prolongation leads to an elevated mitotic index. However, under this condition chromatid segregation and cytokinesis are normal. Using Mad2/YFP-expressing cells, we show the prolongation of mitosis in the absence of p38 activity is directly due to a delay in satisfying the mitotic checkpoint. Inhibiting p38 did not affect the rate of chromosome motion; however, it did lead to the formation of significantly (10%) longer metaphase spindles. From these data we conclude that normal p38 activity is required for the timely stable attachment of all kinetochores to spindle microtubules, but not for the fidelity of the mitotic process. We speculate that p38 activity promotes timely checkpoint satisfaction by indirectly influencing those motor proteins (e.g., Klp10, Klp67A) involved in regulating the dynamics of kinetochore microtubule ends. PMID:20462950

Development and evaluation of a centralised computerised registry for ureteric stents: completing the audit cycle.

PubMed

Davis, N F; Murray, G; O'Connor, T; Browne, C; MacCraith, E; Galvin, D; Mulvin, D; Quinlan, D; Lennon, G

2017-11-01

A forgotten ureteric stent may result in severe renal impairment leading to nephrectomy. To compare the effectiveness of a centralised computerised registry for monitoring ureteric stent activity with a previously established theatre stent logbook system. This prospective audit was performed in two 9-monthly intervals. During the first interval, insertion/removal of a ureteric stent was documented in a specific theatre stent logbook. In the second interval, an electronic centralised computerised registry was developed to document insertion/removal of a ureteric stent onto an accessible hospital server. A computerised traffic-light system was also developed to identify patients with an indwelling stent for >3 months. The primary outcome variable was the number of prolonged indwelling ureteric stents in both groups. During the first time interval, 188 ureteric stents were inserted and 182 (96%) were removed or changed. Six (4%) patients underwent insertion of a ureteric stent for a prolonged period of time (>6 months). This subgroup required complex endourological intervention for stent removal due to encrustation. During the second time interval, 157 ureteric stents were inserted and all patients had their stent removed or changed within 6 months. No patients in this group were lost to follow-up. This study demonstrates that a centralised computerised ureteric stent registry is superior to a conventional logbook for monitoring ureteric stent activity. We propose the introduction a centralised nationalised ureteric stent registry for eliminating the potential for prolonged or forgotten ureteric stents.

FEASIBILITY AND EFFECTIVENESS OF DYADIC PROLONGED EXPOSURE INTERVENTION FOR PREVENTING POSTTRAUMATIC GRIEF IN YOUNG CHILDREN: A CASE REPORT OF TWO SIBLINGS.

PubMed

Rachamim, Lilach

2017-09-01

This article highlights the feasibility of a dyadic prolonged exposure (DPE) intervention (L. Rachamim, I. Mirochnik, L. Helpman, N. Nacasch, & E. Yadin, ) in a 3-year-old preschooler and in a 6-year-old kindergartener immediately following the traumatic death of their younger sibling. It presents a detailed case description of the DPE treatment addressing traumatic grief and includes transcribed treatment dialogue. At the time of treatment termination, both children and caregivers resumed normal functioning. The results suggest that DPE intervention may ameliorate posttraumatic grief symptoms in young children. Controlled studies of preventive interventions for this population are clearly warranted. © 2017 Michigan Association for Infant Mental Health.

Effects of Chitosan Derivative N-[(2-Hydroxy-3-Trimethylammonium)Propyl]Chloride on Anticoagulant Activity of Guinea Pig Plasma.

PubMed

Drozd, N N; Shagdarova, B Ts; Il'ina, A V; Varlamov, V P

2017-07-01

Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 70 aIIa U/kg non-fractionated heparin shortened plasma clotting time (shown by partial activated thromboplastin time, thrombin time, and prothrombin time). Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 1 mg/kg (100 aXa U/kg) low-molecular-weight heparin (clexane) led to shortening of plasma clotting time in the ReaClot Heparin test and to prolongation of plasma amidolytic activity in the factor Xa chromogenic substrate test.

Quantitative description of the effect of stratification on dormancy release of grape seeds in response to various temperatures and water contents

PubMed Central

Wang, W. Q.; Song, S. Q.; Li, S. H.; Gan, Y. Y.; Wu, J. H.; Cheng, H. Y.

2009-01-01

The effect of stratification on dormancy release of grape seeds crossing from the sub- to the supraoptimal range of temperatures and water contents was analysed by modified threshold models. The stratification impacted on dormancy release in three different ways: (i) dormancy was consistently released with prolonged stratification time when stratified at temperatures of <15 °C; (ii) at 15 °C and 20 °C, the stratification effect initially increased, and then decreased with extended time; and (iii) stratification at 25 °C only reduced germinable seeds. These behaviours indicated that stratification could not only release primary dormancy but also induce secondary dormancy in grape seed. The rate of dormancy release changed linearly in two phases, while induction increased exponentially with increasing temperature. The thermal time approaches effectively quantified dormancy release only at suboptimal temperature, but a quantitative method to integrate the occurrence of dormancy release and induction at the same time could describe it well at either sub- or supraoptimal temperatures. The regression with the percentage of germinable seeds versus stratification temperature or water content within both the sub- and supraoptimal range revealed how the optimal temperature (Tso) and water content (Wso) for stratification changed. The Tso moved from 10.6 °C to 5.3 °C with prolonged time, while Wso declined from >0.40 g H2O g DW−1 at 5 °C to ∼0.23 g H2O g DW−1 at 30 °C. Dormancy release in grape seeds can occur across a very wide range of conditions, which has important implications for their ability to adapt to a changeable environment in the wild. PMID:19491305

Prolonged Operative Duration Increases Risk of Surgical Site Infections: A Systematic Review

PubMed Central

Chen, Brian Po-Han; Soleas, Ireena M.; Ferko, Nicole C.; Cameron, Chris G.; Hinoul, Piet

2017-01-01

Abstract Background: The incidence of surgical site infection (SSI) across surgical procedures, specialties, and conditions is reported to vary from 0.1% to 50%. Operative duration is often cited as an independent and potentially modifiable risk factor for SSI. The objective of this systematic review was to provide an in-depth understanding of the relation between operating time and SSI. Patients and Methods: This review included 81 prospective and retrospective studies. Along with study design, likelihood of SSI, mean operative times, time thresholds, effect measures, confidence intervals, and p values were extracted. Three meta-analyses were conducted, whereby odds ratios were pooled by hourly operative time thresholds, increments of increasing operative time, and surgical specialty. Results: Pooled analyses demonstrated that the association between extended operative time and SSI typically remained statistically significant, with close to twice the likelihood of SSI observed across various time thresholds. The likelihood of SSI increased with increasing time increments; for example, a 13%, 17%, and 37% increased likelihood for every 15 min, 30 min, and 60 min of surgery, respectively. On average, across various procedures, the mean operative time was approximately 30 min longer in patients with SSIs compared with those patients without. Conclusions: Prolonged operative time can increase the risk of SSI. Given the importance of SSIs on patient outcomes and health care economics, hospitals should focus efforts to reduce operative time. PMID:28832271

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty

PubMed Central

Lenssen, Ton AF; van Steyn, Mike JA; Crijns, Yvonne HF; Waltjé, Eddie MH; Roox, George M; Geesink, Ruud JT; Brandt, Piet A van den; De Bie, Rob A

2008-01-01

Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Conclusion Although results indicate that prolonged CPM use might have a small short-term effect on RoM, routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered, since neither long-term effects nor transfer to better functional performance was detected. Trial Registration ISRCTN85759656 PMID:18442423

Effect of cimetidine and ranitidine on pharmacokinetics and pharmacodynamics of a single dose of dofetilide

PubMed Central

Abel, Samantha; Nichols, Donald J; Brearley, Christopher J; Eve, Malcolm D

2000-01-01

Aims The aim of this open-label, placebo-controlled, randomized, four-period crossover study was to determine the effects of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of a single dose of dofetilide. Methods Twenty healthy male subjects received 100 or 400 mg twice daily of cimetidine, 150 mg twice daily of ranitidine, or placebo for 4 days. On the second day, a single oral 500 μg dose of dofetilide was administered immediately after the morning doses of cimetidine, ranitidine, or placebo. Treatment periods were separated by 1–2 weeks. Pharmacokinetic parameters were determined from plasma and urinary dofetilide concentrations; prolongation of the QTc interval was determined from three-lead electrocardiograms. Results Ranitidine did not significantly affect the pharmacokinetics or pharmacodynamics of dofetilide; however, a dose-dependent increase in exposure to dofetilide was observed with cimetidine. When dofetilide was administered with 100 and 400 mg of cimetidine, the area under the plasma concentration-time curve of dofetilide increased by 11% and 48% and the maximum plasma dofetilide concentration increased by 11% and 29%, respectively. The respective cimetidine doses reduced renal clearance of dofetilide by 13% and 33% and nonrenal clearance by 5% and 21%. Dofetilide-induced prolongation of the QTc interval was enhanced by cimetidine; the mean maximum change in QTc interval from baseline was increased by 22% and 33% with 100 and 400 mg of cimetidine, respectively. However, the relationship between the prolongation of the QTc interval and plasma dofetilide concentrations was unaffected by cimetidine or ranitidine; a 1 ng ml−1 increase in plasma dofetilide concentration produced a 17–19 ms prolongation of the QTc interval. Dofetilide was well tolerated, with no treatment-related adverse events or laboratory abnormalities. Conclusions These results suggest that cimetidine increased dofetilide exposure by inhibiting renal tubular dofetilide secretion, whereas ranitidine did not. This effect is not an H2-receptor antagonist class effect but is specific to cimetidine. If therapy with an H2-receptor antagonist is required, it is recommended that cimetidine at all doses be avoided; since ranitidine has no effect on dofetilide pharmacokinetics or prolongation of the QTc interval, it can be seen as a suitable alternative. PMID:10606839

Implementation of Prolonged Exposure in the Army: Is Consultation Necessary for Effective Dissemination

DTIC Science & Technology

2014-10-01

University of Pennsylvania, Allison Chernov, was trained to assist with the study at this time. In September 2013, Sally Curtis and Kristen Butcher were...Ronald L CTR USARMY MEDCOM Hoover (US) <ronald.l.hoover.ctr@mail.mil>, Inna R CTR USARMY MEDCOM CDMRP Williams (US) <inna.r.williams.ctr@mail.mil

Effects of in vitro hemodilution with crystalloids, colloids, and plasma on canine whole blood coagulation as determined by kaolin-activated thromboelastography.

PubMed

Morris, Bari R; deLaforcade, Armelle; Lee, Joyce; Palmisano, Joseph; Meola, Dawn; Rozanski, Elizabeth

2016-01-01

To investigate the effects of in vitro hemodilution with lactated Ringers solution (LRS), hetastarch (HES), and fresh frozen plasma (FFP) on whole blood coagulation in dogs as assessed by kaolin-activated thromboelastography. In vitro experimental study. University teaching hospital. Six healthy client-owned dogs. Whole blood was collected and diluted in vitro at a 33% and 67% dilution with either LRS, HES, or FFP. Kaolin-activated thromboelastography was performed on each sample as well as a control. Thromboelastographic parameters R (min), alpha (deg), K (min), and MA (mm) were measured and compared to the sample control for each dilution using mixed model methodology. Prolongation in coagulation times were seen at both dilutions with LRS and HES. There was no significant difference in R times at the 33% dilution, but R time was significantly prolonged at the 67% dilution with HES (P = 0.004). MA was significantly decreased for LRS at both dilutions (P = 0.013, P < 0.001) and more profoundly decreased for HES (P < 0.001, P = 0.006). No significant difference in any parameter was found for FFP. In vitro hemodilution of whole blood with both LRS and HES but not FFP resulted in significant effects on coagulation with HES having a more profound effect. In vivo evaluation of changes in coagulation with various resuscitation fluids is warranted and may be clinically relevant. © Veterinary Emergency and Critical Care Society 2015.

Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease.

PubMed

Lee, David; Lu, Qiaozhi; Sommerfeld, Sven D; Chan, Amanda; Menon, Nikhil G; Schmidt, Tannin A; Elisseeff, Jennifer H; Singh, Anirudha

2017-06-01

Hyaluronic acid (HA) solutions effectively lubricate the ocular surface and are used for the relief of dry eye related symptoms. However, HA undergoes rapid clearance due to limited adhesion, which necessitates frequent instillation. Conversely, highly viscous artificial tear formulations with HA blur vision and interfere with blinking. Here, we developed an HA-eye drop formulation that selectively binds and retains HA for extended periods of time on the ocular surface. We synthesized a heterobifunctional polymer-peptide system with one end binding HA while the other end binding either sialic acid-containing glycosylated transmembrane molecules on the ocular surface epithelium, or type I collagen molecule within the tissue matrix. HA solution was mixed with the polymer-peptide system and tested on both ex vivo and in vivo models to determine its ability to prolong HA retention. Furthermore, rabbit ocular surface tissues treated with binding peptides and HA solutions demonstrated superior lubrication with reduced kinetic friction coefficients compared to tissues treated with conventional HA solution. The results suggest that binding peptide-based solution can keep the ocular surface enriched with HA for prolonged times as well as keep it lubricated. Therefore, this system can be further developed into a more effective treatment for dry eye patients than a standard HA eye drop. Eye drop formulations containing HA are widely used to lubricate the ocular surface and relieve dry eye related symptoms, however its low residence time remains a challenge. We designed a polymer-peptide system for the targeted delivery of HA to the ocular surface using sialic acid or type I collagen as anchors for HA immobilization. The addition of the polymer-peptide system to HA eye drop exhibited a reduced friction coefficient, and it can keep the ocular surface enriched with HA for prolonged time. This system can be further developed into a more effective treatment for dry eye than a standard HA eye drop. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Total donor ischemic time: relationship to early hemodynamics and intensive care morbidity in pediatric cardiac transplant recipients.

PubMed

Rodrigues, Warren; Carr, Michelle; Ridout, Deborah; Carter, Katherine; Hulme, Sara Louise; Simmonds, Jacob; Elliott, Martin; Hoskote, Aparna; Burch, Michael; Brown, Kate L

2011-11-01

Single-center studies have failed to link modest increases in total donor ischemic time to mortality after pediatric orthotopic heart transplant. We aimed to investigate whether prolonged total donor ischemic time is linked to pediatric intensive care morbidity after orthotopic heart transplant. Retrospective cohort review. Tertiary pediatric transplant center in the United Kingdom. Ninety-three pediatric orthotopic heart transplants between 2002 and 2006. Total donor ischemic time was investigated for association with early post-orthotopic heart transplant hemodynamics and intensive care unit morbidities. Of 43 males and 50 females with median age 7.2 (interquartile range 2.2, 13.0) yrs, 62 (68%) had dilated cardiomyopathy, 20 (22%) had congenital heart disease, and nine (10%) had restrictive cardiomyopathy. The mean total donor ischemic time was 225.9 (sd 65.6) mins. In the first 24 hrs after orthotopic heart transplant, age-adjusted mean arterial blood pressure increased (p < .001), mean pulmonary arterial pressure fell (p = .012), but central venous pressure (p = .58) and left atrial pressure (p = .20) were unchanged. After adjustment for age, primary diagnosis, pre-orthotopic heart transplant mechanical support, and marginal donor factors, longer total donor ischemic time was significantly associated with lower mean arterial blood pressure (p < .001) in the first 24 hrs after orthotopic heart transplant, longer post-orthotopic heart transplant mechanical ventilation (p = .03), longer post-orthotopic heart transplant stay in the intensive care unit (p = .004), and longer post-orthotopic heart transplant stay in hospital (p = .02). Total donor ischemic time was not related to levels of mean pulmonary arterial pressure (p = .62), left atrial pressure (p = .38), or central venous pressure (p = .76) early after orthotopic heart transplant. Prolonged total donor ischemic time has an adverse effect on the donor organ, contributing to lower mean arterial blood pressure, as well as more prolonged ventilation and intensive care unit and hospital stays post-orthotopic heart transplant, reflecting increased morbidity.

Effectiveness of Cognitive Processing Therapy and Prolonged Exposure in the Department of Veterans Affairs.

PubMed

Rutt, Benjamin T; Oehlert, Mary E; Krieshok, Thomas S; Lichtenberg, James W

2018-04-01

Objective This study evaluated the effectiveness of cognitive processing therapy and prolonged exposure in conditions reflective of current clinical practice within the Veterans Health Administration. Method This study involved a retrospective review of 2030 charts. A total of 750 veterans from 10 U.S. states who received cognitive processing therapy or prolonged exposure in individual psychotherapy were included in the study (participants in cognitive processing therapy, N = 376; participants in prolonged exposure, N = 374). The main dependent variable was self-reported posttraumatic stress disorder symptoms as measured by total scores on the Posttraumatic Stress Disorder Checklist. The study used multilevel modeling to evaluate the absolute and relative effectiveness of both treatments and determine the relationship between patient-level variables and total Posttraumatic Stress Disorder Checklist scores during treatment. Results Cognitive processing therapy and prolonged exposure were equally effective at reducing total Posttraumatic Stress Disorder Checklist scores. Veterans who completed therapy reported significantly larger reductions in the Posttraumatic Stress Disorder Checklist than patients who did not complete therapy. There were no significant differences in the improvement of posttraumatic stress disorder symptoms with respect to age and three racial/ethnic groups (Caucasian, African American, and Hispanic). Conclusions Cognitive processing therapy and prolonged exposure were shown to be effective in conditions highly reflective of clinical practice and with a highly diverse sample of veterans. Challenges related to dropout from trauma focused therapy should continue to be researched.

The Antithrombotic and Fibrinolytic Effect of Natto in Hypercholesterolemia Rats

PubMed Central

Park, Kum-Ju; Kang, Jung Il; Kim, Tae-Seok; Yeo, Ik-Hyun

2012-01-01

Antithrombotic and fibrinolytic activity of natto was evaluated on platelet aggregation in vitro and in vivo. Natto showed inhibitory effects on platelet aggregation induced by adenosine 5′diphosphate (ADP) and collagen. Orally administered natto also showed fibrinolytic activity in hypercholesterolemia rats. Normal levels of natto, when administered for four weeks, shortened euglobulin clot lysis time (ECLT) and prolonged partial thromboplastin time (PATT) significantly compared to non-treated group. In addition, the natto treatment decreased total cholesterol in serum. These results showed that intake of normal levels of natto can elicit antithrombotic and fibrinolytic effects, suggesting its consumption may improve blood circulation. PMID:24471066

Long-term potentiation in the dentate gyrus in freely moving rats is reinforced by intraventricular application of norepinephrine, but not oxotremorine.

PubMed

Almaguer-Melian, William; Rojas-Reyes, Yeneissy; Alvare, Armando; Rosillo, Juan C; Frey, Julietta U; Bergado, Jorge A

2005-01-01

Growing evidence suggests that processes of synaptic plasticity, such as long-term potentiation (LTP) occurring in one synaptic population, can be modulated by consolidating afferents from other brain structures. We have previously shown that an early-LTP lasting less than 4 h (E-LTP) in the dentate gyrus can be prolonged by stimulating the basolateral amygdala, the septum or the locus coeruleus within a specific time window. Pharmacological experiments have suggested that noradregeneric (NE) and/or cholinergic systems might be involved in these effects. We have therefore investigated whether the direct intraventricular application of agonists for NE- or muscarinic receptors is able to modulate synaptic plasticity. E-LTP was induced at the dentate gyrus of freely moving rats using a mild tetanization protocol that induces only an E-LTP. NE or oxotremorine (OXO) were applied icv 10 min after the tetanus. Results show that low doses of NE (1.5 and 5 nM) effectively prolong LTP. A higher dose (50 nM) was not effective. None of the OXO doses employed (5, 25, and 50 nM) showed similar effects. These results stress the importance of transmitter-specific modulatory influences on the time course of synaptic plasticity, in particular NE whose application mimics the reinforcing effect of directly stimulating limbic structures on LTP.

Flos Albiziae aqueous extract and its active constituent quercetin potentiate the hypnotic effect of pentobarbital via the serotonergic system

PubMed Central

YE, MENG-FEI; LIU, ZHENG; LOU, SHU-FANG; CHEN, ZHEN-YONG; YU, AI-YUE; LIU, CHUN-YAN; YU, CHAO-YANG; ZHANG, HUA-FANG; ZHANG, JIAN

2015-01-01

Flos albiziae (FA) is reportedly used for treatment of insomnia and anxiety in traditional medicine. The hypnotic effect of an extract of FA (FAE) and its constituent quercetin [2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, QR] was examined in mice. QR is a widely distributed natural flavonoid abundant in FA flowers and other tissues. The possible mechanisms underlying the hypnotic effects of FAE and QR were investigated using behavioral pharmacology. FAE and QR significantly potentiated pentobarbital-induced [50 mg/kg, intraperitoneal (ip)] sleep (prolonged sleeping time; shortened sleep latency) in a dose-dependent manner, and these effects were augmented by administration of 5-hydroxytryptophan (5-HTP), a precursor of 5-hydroxytryptamine. With a sub-hypnotic dose of pentobarbital (28 mg/kg, ip), FAE and QR significantly increased the rate of sleep onset and were synergistic with 5-HTP (2.5 mg/kg, ip). Pretreatment with p-chlorophenylalanine, an inhibitor of tryptophan hydroxylase, significantly decreased sleeping time and prolonged sleep latency in pentobarbital-treated mice, whereas FAE and QR significantly reversed this effect. Data show that FAE and QR have hypnotic activity, possibly mediated by the serotonergic system. The present study offers a rationale for the use of FA in treating sleep disorders associated with serotonin system dysfunction. PMID:26623026

Imagining the alternatives to life prolonging treatments: elders' beliefs about the dying experience.

PubMed

Winter, Laraine; Parker, Barbara; Schneider, Melissa

2007-08-01

Deciding for or against a life-prolonging treatment represents a choice between prolonged life and death. When the death alternative is not described, individuals must supply their own assumptions. How do people imagine the experience of dying? We asked 40 elderly people open-ended questions about dying without 4 common life-prolonging treatments, eliciting beliefs about pain, length of time, loneliness, and palliative care. Beliefs were diverse, loneliness was commonly assumed, and palliation was rarely mentioned spontaneously. Results underscore needs for improved understanding of the dying process and palliative care and for fuller communication between patients and healthcare providers.

The effect of prolonged standing on touch sensitivity threshold of the foot: a pilot study.

PubMed

Wiggermann, Neal E; Werner, Robert A; Keyserling, W Monroe

2012-02-01

To determine the effect of prolonged standing on touch sensitivity of the foot. An observational study with replications. University laboratory. Ten healthy college students (5 men and 5 women), with a mean ± SD age of 23.5 ± 4.1 years and body mass of 67.4 ± 12.6 kg. Semmes-Weinstein monofilament tests were administered to 12 locations on the dorsal and plantar surfaces of the foot before and after 4 hours of standing. These locations were formed into several groupings (toes, metatarsal heads, midfoot, heel, all plantar sites, all dorsal sites), and paired t-tests were used to test for significant changes in sensitivity threshold after standing. The difference between sensitivity thresholds measured before and after standing for different locations on the foot. The average of all sensitivity thresholds on the plantar surface of the foot decreased (indicating increased sensitivity) from 0.56 to 0.36 g (P < .01) after 4 hours of prolonged standing. This change in threshold equated to a difference of 1 Semmes-Weinstein monofilament level. Changes in the sensitivity threshold of the dorsal aspect of the foot were not significant. Analysis of the results suggests that the plantar foot has greater sensitivity to touch after prolonged standing. These findings may be useful for identifying potential unintended bias in clinical touch sensitivity testing. Future research is necessary to understand the underlying mechanisms for this sensitivity change and to determine the onset and recovery times for sensitivity changes. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A.

PubMed

Ku, Sae-Kwang; Bae, Jong-Sup

2014-03-01

Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. However, antiplatelet, anticoagulant, and profibrinolytic properties of WFA have not been studied. In this study, the anticoagulant activities of WFA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), fibrin polymerization, platelet aggregation, thrombus formation, and the activities of cell-based thrombin and activated factor X (FXa). The effects of WFA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Our data showed that WFA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, FeCl3-induced thrombus formation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. WFA prolonged in vivo and ex vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by WFA. Collectively, these results indicate that WFA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of Metal and Plastic Disposable Laryngoscope Blade with Reusable Macintosh Blade in Difficult and Inhalation Injury Airway Scenario: A Manikin Study.

PubMed

Moritz, Andreas; Heinrich, Sebastian; Irouschek, Andrea; Birkholz, Torsten; Prottengeier, Johannes; Schmidt, Joachim

2017-01-01

Single-use plastic blades (SUPB) and single-use metal blades (SUMB) for direct laryngoscopy and tracheal intubation have not yet been compared with reusable metal blades (RUMB) in difficult airway scenarios. The purpose of our manikin study was to compare the effectiveness of these different laryngoscope blades in a difficult airway scenario, as well as in a difficult airway scenario with simulated severe inhalation injury. Thirty anesthetists performed tracheal intubation (TI) with each of the three laryngoscope blades in the two scenario manikins. In the inhalation injury scenario, SUPB were associated with prolonged intubation times when compared with the metal blades. In the inhalation injury scenario, both metal laryngoscope blades provided a quicker, easier, and safer TI. In the difficult airway scenario, intubation times were significantly prolonged in the SUPB group in comparison to the RUMB group, but there were no significant differences between the SUPB and the SUMB. In this scenario, the RUMB demonstrated the shortest intubation times and seems to be the most effective device. Generally, results are in line with previous studies showing significant disadvantages of SUPB in both manikin scenarios. Therefore, metal blades might be beneficial, especially in the airway management of patients with inhalation injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of repaglinide as a therapeutic drug for glioblastoma multiforme.

PubMed

Xiao, Zui Xuan; Chen, Ruo Qiao; Hu, Dian Xing; Xie, Xiao Qiang; Yu, Shang Bin; Chen, Xiao Qian

2017-06-17

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape. Drug repositioning in Connectivity Map by using the gene expression signature identified repaglinide, a first-line drug for diabetes mellitus, as the most promising novel drug for GBM. In vitro experiments demonstrated that repaglinide significantly inhibited the proliferation and migration of human GBM cells. In vivo experiments demonstrated that repaglinide prominently prolonged the median survival time of mice bearing orthotopic glioma. Mechanistically, repaglinide significantly reduced Bcl-2, Beclin-1 and PD-L1 expression in glioma tissues, indicating that repaglinide may exert its anti-cancer effects via apoptotic, autophagic and immune checkpoint signaling. Taken together, repaglinide is likely to be an effective drug to prolong life span of GBM patients. Copyright © 2017. Published by Elsevier Inc.

Prolonged striatal disinhibition as a chronic animal model of tic disorders.

PubMed

Vinner, Esther; Israelashvili, Michal; Bar-Gad, Izhar

2017-12-01

Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABA A antagonists into the striatum, leading to temporary disinhibition. The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Wearable Beat-to-Beat Blood Pressure Monitor

NASA Technical Reports Server (NTRS)

Lee, Yong Jin

2015-01-01

Linea Research Corporation has developed a wearable noninvasive monitor that provides continuous blood pressure and heart rate measurements in extreme environments. Designed to monitor the physiological effects of astronauts' prolonged exposure to reduced-gravity environments as well as the effectiveness of various countermeasures, the device offers wireless connectivity to allow transfer of both real-time and historical data. It can be modified to monitor the health status of astronaut crew members during extravehicular missions.

The effectiveness of Grief-Help, a cognitive behavioural treatment for prolonged grief in children: study protocol for a randomised controlled trial.

PubMed

Spuij, Mariken; Prinzie, Peter; Dekovic, Maja; van den Bout, Jan; Boelen, Paul A

2013-11-20

There is growing recognition of a syndrome of disturbed grief referred to as prolonged grief disorder (PGD). PGD is mostly studied in adults, but clinically significant PGD symptoms have also been observed in children and adolescents. Yet, to date no effective treatment for childhood PGD exists. The aims of this study are: (1) to investigate the effectiveness of Grief-Help, a nine-session cognitive-behavioural treatment for childhood PGD, combined with five sessions of parental counselling, immediately after the treatment and at three, six and twelve months follow-up; (2) to examine tentative mediators of the effects of Grief-Help, (i.e., maladaptive cognitions and behaviours and positive parenting), and (3) to determine whether demographic variables, child personality, as well as symptoms of PGD, anxiety, and depression in parents moderate the treatment effectiveness. We will conduct a Randomised Controlled Trial (RCT) in which 160 children and adolescents aged 8-18 years are randomly allocated to cognitive behavioural Grief-Help or to a supportive counselling intervention; both treatments are combined with five sessions of parental counselling. We will recruit participants from clinics for mental health in the Netherlands. The primary outcome measure will be the severity of Prolonged Grief Disorder symptoms according to the Inventory of Prolonged Grief for Children (IPG-C). Secondary outcomes will include PTSD, depression and parent-rated internalizing and externalizing problems. Mediators like positive parenting and maladaptive cognitions and behaviours will be identified. We will also examine possible moderators including demographic variables (e.g. time since loss, cause of death), psychopathology symptoms in parents (PGD, anxiety and depression) and child personality. Assessments will take place in both groups at baseline, after the treatment-phase and three, six and twelve months after the post-treatment assessment. We aim to contribute to the improvement of mental health care for children and adolescents suffering from loss. By comparing Grief-Help with supportive counselling, and by investigating mediators and moderators of its effectiveness we hope to provide new insights in the effects of interventions for bereaved children, and their mechanisms of change. Netherlands Trial Register NTR3854.

Primiparous women's preferences for care during a prolonged latent phase of labour.

PubMed

Ängeby, Karin; Wilde-Larsson, Bodil; Hildingsson, Ingegerd; Sandin-Bojö, Ann-Kristin

2015-10-01

To investigate primiparous women's preferences for care during a prolonged latent phase of labour. A qualitative study based on focus groups and individual interviews and analysed with inductive content analysis. Sixteen primiparous women with a prolonged latent phase of labour >18 hours were interviewed in five focus groups (n = 11) or individually (n = 5). One main category emerged "Beyond normality - a need of individual adapted guidance in order to understand and manage an extended latent phase of labour" which covers the women's preferences during the prolonged latent phase. Five categories were generated from the data: "A welcoming manner and not being rejected", "Individually adapted care", "Important information which prepares for reality and coping", "Participation and need for feedback" and "Staying nearby the labour ward or being admitted for midwifery support". Women with a prolonged latent phase of labour sought to use their own resources, but their needs for professional support increased as time passed. A welcoming attitude from an available midwife during the latent phase created a feeling of security, and personally adapted care was perceived positively. Women with a prolonged latent phase of labour preferred woman-centred care. Midwives play an important role in supporting these women. Women's need for midwifery-support increases as the time spent in latent phase increases. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of prolonged hypokinesia on resistance of resistive vessels in rats

NASA Technical Reports Server (NTRS)

Saltykova, V. A.

1982-01-01

Under the effect of prolonged hypokinesia, the perfusion pressure in resistive vessels, measured under conditions of deep anesthesia and complete denervation, increased by approximately the same degree as arterial pressure in non-anesthetized animals. The increase in arterial, perfusion pressure and the resistance of resistive vessels in animals subjected to prolonged hypokinesia was accompanied by an increase in adrenoreactivity. During prolonged hypokinesia, partial obliteration of the vascular bed of the skeletal muscles plays a significant role in the observed increase in resistance of vessels of the extremities. The increase in adrenoreactivity of the vessels during hypokinesia may be realized as a partial case of an increase in the adrenoreactivity of structures whose innervation is disturbed.

Plasma phenylalanine and tyrosine responses to different nutritional conditions (fasting/postprandial) in patients with phenylketonuria: effect of sample timing.

PubMed

van Spronsen, F J; van Rijn, M; van Dijk, T; Smit, G P; Reijngoud, D J; Berger, R; Heymans, H S

1993-10-01

To evaluate the adequacy of dietary treatment in patients with phenylketonuria, the monitoring of plasma phenylalanine and tyrosine concentrations is of great importance. The preferable time of blood sampling in relation to the nutritional condition during the day, however, is not known. It was the aim of this study to define guidelines for the timing of blood sampling with a minimal burden for the patient. Plasma concentrations of phenylalanine and tyrosine were measured in nine patients with phenylketonuria who had no clinical evidence of tyrosine deficiency. These values were measured during the day both after a prolonged overnight fast, and before and after breakfast. Phenylalanine showed a small rise during prolonged fasting, while tyrosine decreased slightly. After an individually tailored breakfast, phenylalanine remained stable, while tyrosine showed large fluctuations. It is concluded that the patient's nutritional condition (fasting/postprandial) is not important in the evaluation of the phenylalanine intake. To detect a possible tyrosine deficiency, however, a single blood sample is not sufficient and a combination of a preprandial and postprandial blood sample on the same day is advocated.

Tafenoquine at therapeutic concentrations does not prolong fridericia-corrected QT interval in healthy subjects

PubMed Central

Green, Justin A; Patel, Apurva K; Patel, Bela R; Hussaini, Azra; Harrell, Emma J; McDonald, Mirna J; Carter, Nick; Mohamed, Khadeeja; Duparc, Stephan; Miller, Ann K

2014-01-01

Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18–65 years were randomized to one of five treatment groups (n = 52 per group) to receive placebo, tafenoquine 300, 600, or 1200 mg, or moxifloxacin 400 mg (positive control). Lack of effect was demonstrated if the upper 90% CI of the change from baseline in QTcF following supratherapeutic tafenoquine 1200 mg versus placebo (ΔΔQTcF) was <10 milliseconds for all pre-defined time points. The maximum ΔΔQTcF with tafenoquine 1200 mg (n = 50) was 6.39 milliseconds (90% CI 2.85, 9.94) at 72 hours post-final dose; that is, lack of effect for prolongation of cardiac depolarization was demonstrated. Tafenoquine 300 mg (n = 48) or 600 mg (n = 52) had no effect on ΔΔQTcF. Pharmacokinetic/pharmacodynamic modeling of the tafenoquine–QTcF concentration–effect relationship demonstrated a shallow slope (0.5 ms/μg mL–1) over a wide concentration range. For moxifloxacin (n = 51), maximum ΔΔQTcF was 8.52 milliseconds (90% CI 5.00, 12.04), demonstrating assay sensitivity. In this thorough QT/QTc study, tafenoquine did not have a clinically meaningful effect on cardiac repolarization. PMID:24700490

Tafenoquine at therapeutic concentrations does not prolong Fridericia-corrected QT interval in healthy subjects.

PubMed

Green, Justin A; Patel, Apurva K; Patel, Bela R; Hussaini, Azra; Harrell, Emma J; McDonald, Mirna J; Carter, Nick; Mohamed, Khadeeja; Duparc, Stephan; Miller, Ann K

2014-09-01

Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18-65 years were randomized to one of five treatment groups (n = 52 per group) to receive placebo, tafenoquine 300, 600, or 1200 mg, or moxifloxacin 400 mg (positive control). Lack of effect was demonstrated if the upper 90% CI of the change from baseline in QTcF following supratherapeutic tafenoquine 1200 mg versus placebo (ΔΔQTcF) was <10 milliseconds for all pre-defined time points. The maximum ΔΔQTcF with tafenoquine 1200 mg (n = 50) was 6.39 milliseconds (90% CI 2.85, 9.94) at 72 hours post-final dose; that is, lack of effect for prolongation of cardiac depolarization was demonstrated. Tafenoquine 300 mg (n = 48) or 600 mg (n = 52) had no effect on ΔΔQTcF. Pharmacokinetic/pharmacodynamic modeling of the tafenoquine-QTcF concentration-effect relationship demonstrated a shallow slope (0.5 ms/μg mL(-1) ) over a wide concentration range. For moxifloxacin (n = 51), maximum ΔΔQTcF was 8.52 milliseconds (90% CI 5.00, 12.04), demonstrating assay sensitivity. In this thorough QT/QTc study, tafenoquine did not have a clinically meaningful effect on cardiac repolarization. © 2014, The American College of Clinical Pharmacology.

The effects of diltiazem and metoprolol in QTc prolongation due to amitriptyline intoxication.

PubMed

Basol, Nursah; Erbas, Oytun

2016-01-01

Amitriptyline, a frequently used tricyclic antidepressant agent, has powerful cardiotoxic effects especially in high doses. Serum and urine levels of amitriptyline dosages are not correlated with severity of toxicity; therefore, it increases the importance of electrocardiography (ECG) abnormalities. The prolongation of QTc can be a predictive marker for cardiotoxicity. Hence, in this study, it is aimed to evaluate possible effects of metoprolol and diltiazem in amitriptyline toxicity. The rats were separated into four groups. First one was control group, the second was the amitriptyline + saline group, third one was the amitriptyline + metoprolol group, and forth one was the amitriptyline + diltiazem group. ECG were recorded on rats under anesthesia. In amitriptyline group, QTc duration was prolonged compared with all other groups. The prolongation of QTc was shorter in amitriptyline + metoprolol group and amitriptyline + diltiazem group than amitriptyline group (p < 0.01 and p < 0.01, respectively). According to the results, it is possible to report ameliorating effects of both metoprolol and diltiazem on QTc prolongation related with amitriptyline intoxication. With further studies, these agents may be used for amitriptyline toxicity and besides, they may be used for patients in cardiovascular risk groups who take amitriptyline treatment regularly. © The Author(s) 2015.

TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets.

PubMed

Xia, Luxi; Bartlett, Donald; Leiter, J C

2011-04-30

Elevating body temperature or just the temperature of the dorsal medulla by approximately 2°C prolongs the laryngeal chemoreflex (LCR) in decerebrate neonatal piglets. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) receptors in the nucleus of the solitary tract (NTS) mediate thermal prolongation of the LCR. We studied the effect of a selective TRPV1 receptor antagonist on thermal prolongation of the LCR, and we tested the effect of a TRPV1 agonist on the duration of the LCR under normothermic conditions. We studied 37 decerebrate neonatal piglets between the ages of post-natal days 4 and 7. The TRPV1 receptor antagonist, 5'-iodoresiniferatoxin (65μM/L in 100nL), blocked thermal prolongation of the LCR when injected bilaterally into the region of the NTS. The TRPV1 agonist, resiniferatoxin (0.65-1.0mM/L in 100nL), prolonged the LCR after bilateral injection into the NTS even when the body temperature of each piglet was normal. The effect of the TRPV1 agonists could be blocked by treatment with the GABA(A) receptor antagonist, bicuculline, whether given intravenously (0.3mg/kg) or focally injected bilaterally into the NTS (10mM in 100nL). We conclude that TRPV1 receptors in the NTS mediate thermal prolongation of the LCR. Copyright © 2011 Elsevier B.V. All rights reserved.

Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched study.

PubMed

Lee, Hakmin; Song, Byung D; Byun, Seok-Soo; Lee, Sang E; Hong, Sung K

2018-01-01

To analyse the effect of prolonged warm ischaemia time (WIT) on long-term renal function after partial nephrectomy (PN), as controversy still exists as to whether prolonged WIT adversely affects the incidence of chronic kidney disease (CKD) after PN. We reviewed data from 1816 patients who underwent PN for a clinical T1 renal tumour. The propensity scores for prolonged WIT were calculated with the shorter WIT group (<30 min) matched to the longer WIT group (≥30 min) in a 2:1 ratio. Multivariate analysis was used to determine independent predictors for occurrence of postoperative CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 ] and major renal function deterioration (MRFD; defined as an eGFR decrease of ≥25% postoperatively). After propensity score matching, there was no significant difference in CKD-free survival between the two WIT groups (P = 0.787). Furthermore, longer WIT did not show any significant associations with postoperative CKD-free survival [hazard ratio (HR) 1.002, 95% confidence interval (CI) 0.989-1.015; P = 0.765) and MRFD-free survival (HR 1.014, 95% CI 1.000-1.028; P = 0.055). From further subgroup analyses using more specific WIT thresholds (≤20, 21-30, 31-40, 41-50, ≥50 min) and status of preoperative CKD, no significant differences were noted in CKD and MRFD-free survival amongst the subgroups (all P > 0.05). Prolonged WIT was not associated with increased incidence of CKD or MRFD after PN. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

[Effect of imidapril on the effective refractory period and sodium current of ventricular noninfarction zone in healed myocardial infarction].

PubMed

Li, Yang; Niu, Hui-Yan; Liu, Nian; Zhang, Cun-Tai; Lu, Zai-Ying; Wang, Shi-Wen

2005-07-01

To investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models. Rabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded. The ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group. IMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.

Effect of adding acid solution on setting time and compressive strength of high calcium fly ash based geopolymer

NASA Astrophysics Data System (ADS)

Antoni, Herianto, Jason Ghorman; Anastasia, Evelin; Hardjito, Djwantoro

2017-09-01

Fly ash with high calcium oxide content when used as the base material in geopolymer concrete could cause flash setting or rapid hardening. However, it might increase the compressive strength of geopolymer concrete. This rapid hardening could cause problems if the geopolymer concrete is used on a large scale casting that requires a long setting time. CaO content can be indicated by pH values of the fly ash, while higher pH is correlated with the rapid setting time of fly ash-based geopolymer. This study investigates the addition of acid solution to reduce the initial pH of the fly ash and to prolong the setting time of the mixture. The acids used in this study are hydrochloric acid (HCl), sulfuric acid (H2 SO4), nitric acid (HNO3) and acetic acid (CH3 COOH). It was found that the addition of acid solution in fly ash was able to decrease the initial pH of fly ash, however, the initial setting time of geopolymer was not reduced. It was even faster than that of the control mixture. The acid type causes various influence, depending on the fly ash properties. In addition, the use of acid solution in fly ash reduces the compressive strength of geopolymer mortar. It is concluded that the addition of acid solution cannot prolong the rapid hardening of high calcium fly ash geopolymer, and it causes adverse effect on the compressive strength.

Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

PubMed

Mao, Sheng-Chun; Chang, Chih-Hua; Wu, Chia-Chen; Orejarena, M Juliana; Orejanera, Maria Juliana; Manzoni, Olivier J; Gean, Po-Wu

2013-01-01

Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

Reversal of Apixaban Induced Alterations in Hemostasis by Different Coagulation Factor Concentrates: Significance of Studies In Vitro with Circulating Human Blood

PubMed Central

Arellano-Rodrigo, Eduardo; Roquer, Jaume; Reverter, Joan Carles; Sanz, Victoria Veronica; Molina, Patricia; Lopez-Vilchez, Irene; Diaz-Ricart, Maribel; Galan, Ana Maria

2013-01-01

Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s−1. The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM and perfusion studies. Our results indicate that rFVIIa, PCCs and aPCCs have the potential to restore platelet and fibrin components of the hemostasis previously altered by apixaban. PMID:24244342

Very prolonged liposomal amphotericin B use leading to a lysosomal storage disease.

PubMed

Michot, J M; Gubavu, C; Fourn, E; Maigne, G; Teicher, E; Angoulvant, A; Blanche, S; Lortholary, O; Coilly, A; Duclos-Vallée, J C; Sebagh, M; Guettier, C; Aumont, C; Delfraissy, J F; Lambotte, O

2014-06-01

Amphotericin B is a powerful polyene antifungal drug used for treating systemic fungal infections and is usually administered for a short period. Side effects after prolonged use are unknown in humans. Here we report the case of a 28-year-old man suffering from chronic granulomatous disease (CGD), treated for invasive cerebral aspergillosis with liposomal amphotericin B (L-AmB) for a very long time (8 consecutive years). We describe the efficacy and safety of this treatment in the long term. Aspergillosis was kept under control as long as L-AmB therapy was maintained, but relapsed when the dose was reduced. No overt renal toxicity was noted. The patient gradually developed hepatosplenomegaly and pancytopenia. Abnormalities of bone marrow were similar to the sea-blue histiocyte syndrome. Liver biopsy showed images of nodular regenerative hyperplasia related to CGD as well as a histiocytic storage disease. We discuss the very prolonged use of L-AmB leading to the development of a lysosomal storage disease. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Associations of leisure-time sitting in cars with neighborhood walkability.

PubMed

Koohsari, Mohammad Javad; Sugiyama, Takemi; Kaczynski, Andrew T; Owen, Neville

2014-08-01

Too much sitting, including time spent sitting in cars, is associated with poor health outcomes. Identifying the built-environment attributes that may reduce vehicular sitting time can inform future initiatives linking the public health, urban design, and transportation sectors. Data collected in 2003-2004 from adult residents (n = 2521) of Adelaide, Australia were used. Logistic regression analyses examined associations of prolonged time spent sitting in cars during leisure time (30 min/day or more) with neighborhood walkability and its components (dwelling density; intersection density; land use mix; net retail area ratio). Lower overall walkability was significantly associated with a higher odds (OR = 1.43, 95% CI: 1.21-1.70) of spending prolonged time in cars. For analyses with walkability components, lower net retail area ratio, lower residential density, and lower intersection density were significantly associated with prolonged sitting in cars. This study found that residents of high walkable neighborhoods tended to spend less time sitting in cars. In particular, higher net retail area ratio, an indicator of tightly spaced commercial areas, was strongly associated with less time in cars. Policy and planning initiatives to reduce car use require further evidence, particularly on the influence of neighborhood retail areas.

The Connection between Pupils' School Success and Their Inclusiveness in Extracurricular and Out-of-School Activities in Croatia

ERIC Educational Resources Information Center

Vukic, Violeta Valjan; Zrilic, Smiljana

2016-01-01

The school, with its activities as an upbringing and educational institute, influences all segments of a pupil's effective development. Besides teaching as its basic activity, the school should take over part of the care and responsibility for the pupil's free time and "use" it for "prolonged" upbringing activity. Today…

The effect of energy accumulation and boundary slip on laminar flow between rotating plates

NASA Astrophysics Data System (ADS)

Wu, Zhenpeng; Zeng, Liangcai; Chen, Keying; Jin, Xiaohong; Wu, Shiqian

2018-02-01

The poor operating conditions of fluid lubrication equipment during the start-up process are due to the resistance of the high-viscosity lubricating liquid. Moreover, the excessive reduction in fluid viscosity due to the elevated temperature resulting from power consumption during prolonged operation is not conducive to the generation of dynamic pressure. In this study, we examine the effect of energy accumulation and boundary slip on the laminar flow of a liquid between a pair of rotating plates. The experiments are conducted using a rotary rheometer, with polymethyl methacrylate (PMMA) as the thermal insulation material and polytetrafluoroethylene (PTFE) as the slip drag reduction material, and a three-dimensional simulation model is established. This model is derived by combining the energy equation including the slip length and the heat conduction equation. Thus, the temperature changes over time are predicted by this model, and the model accuracy is verified by experiments. The results reveal the following points: 1) boundary slips function as a drag reduction mechanism for short-time continuous operation; 2) under prolonged operation, the slip reduces the extent of the oil viscosity decrease and clear control of the elevated temperature by the boundary slip is observed.

Changes in cell proliferation kinetics in the mouse cerebellum after total asphyxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshioka, H.; Mino, M.; Morikawa, Y.

1985-12-01

This study was undertaken to investigate the effects of neonatal asphyxia on brain development, with special reference to the kinetics of neuronal proliferation by using autoradiography. For 30 minutes, two-day-old suckling mice, Jcl:ICR strain, were put into a chamber which was constantly flushed with 100% CO/sub 2/ gas. After the exposure to asphyxia, 29% of the mice survived. Cell cycle studies were carried out at two days and at seven days on the external matrix cells, the precursor of the granule cells, at the external granular layer of the cerebellum from CO/sub 2/-exposed and control mice by /sup 3/H-thymidine autoradiography.more » At two days the generation time of the control mice was about 15 hours, whereas that of the asphyxiated mice was about 17 hours. The prolongation of the generation time in the asphyxiated mice was caused mainly by a delay in the G2 phase. This prolongation was apparent for about five days and thereafter growth caught up. These results suggest that neonatal asphyxia has an adverse effect on cerebellar neuronal proliferation that may revert to normal spontaneously in older animals.« less

Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With Adverse Outcomes

DTIC Science & Technology

2010-07-01

using the FVII coagulant activity (FVII:C) assay, a one- stage assay using thromboplastin tissue factor , which quantifies FVII clotting activity in...and the resultant production of dysfunctional factors II, VII, and X. This study focused on PT specifically because this measure examines the TF...ORIGINAL ARTICLE Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With

The Need for Future Alternatives: An Investigation of the Experiences and Future of Older Parents Caring for Offspring with Learning Disabilities over a Prolonged Period of Time

ERIC Educational Resources Information Center

Cairns, Deborah; Tolson, Debbie; Brown, Jayne; Darbyshire, Chris

2013-01-01

This article reports on the results of a qualitative study (in-depth interviews) carried out in the United Kingdom as part of a larger (two-phased) study investigating the experiences, health and future perspectives of older parent carers (six mothers and two fathers) of offspring with learning disabilities over a prolonged period of time. The…

Occurrence of amylose-lipid complexes in teff and maize starch biphasic pastes.

PubMed

Wokadala, Obiro Cuthbert; Ray, Suprakas Sinha; Emmambux, Mohammad Naushad

2012-09-01

The occurrence of amylose-lipid complexes was determined in maize and teff starch biphasic pastes i.e. peak viscosity pastes at short and prolonged pasting times. Maize and teff starches were pasted for 11.5 and 130 min with or without added stearic acid followed by thermo-stable alpha-amylase hydrolysis in a rapid visco-analyzer. X-ray diffraction analysis of pastes before and residues after hydrolysis showed crystalline V-amylose diffraction patterns for the starches pasted for a prolonged time with added stearic acid while less distinct V-amylose patterns with non-complexed stearic acid peaks were observed with a short pasting time. Differential scanning calorimetry of pastes before and residues after paste hydrolysis showed that Type I amylose-lipid complexes were formed after pasting for the short duration with added stearic acid, while Type II complexes are formed after pasting for the prolonged time. The present research provides evidence that amylose-lipid complexes play an important role in starch biphasic pasting. Copyright © 2012 Elsevier Ltd. All rights reserved.

The influence of wearing compression stockings on performance indicators and physiological responses following a prolonged trail running exercise.

PubMed

Vercruyssen, Fabrice; Easthope, Christopher; Bernard, Thierry; Hausswirth, Christophe; Bieuzen, Francois; Gruet, Mathieu; Brisswalter, Jeanick

2014-01-01

The objective of this study was to investigate the effects of wearing compression socks (CS) on performance indicators and physiological responses during prolonged trail running. Eleven trained runners completed a 15.6 km trail run at a competition intensity whilst wearing or not wearing CS. Counter movement jump, maximal voluntary contraction and the oxygenation profile of vastus lateralis muscle using near-infrared spectroscopy (NIRS) method were measured before and following exercise. Run time, heart rate (HR), blood lactate concentration and ratings of perceived exertion were evaluated during the CS and non-CS sessions. No significant difference in any dependent variables was observed during the run sessions. Run times were 5681.1 ± 503.5 and 5696.7 ± 530.7 s for the non-CS and CS conditions, respectively. The relative intensity during CS and non-CS runs corresponded to a range of 90.5-91.5% HRmax. Although NIRS measurements such as muscle oxygen uptake and muscle blood flow significantly increased following exercise (+57.7% and + 42.6%,+59.2% and + 32.4%, respectively for the CS and non-CS sessions, P<0.05), there was no difference between the run conditions. The findings suggest that competitive runners do not gain any practical or physiological benefits from wearing CS during prolonged off-road running.

The Effect on Moderate Altitude UPON Human Gastric Emptying Time

DTIC Science & Technology

1952-03-01

physiological aliment . The emptying time, therefore, of a mixture of barium and food may perhaps differ somewhat from that of food alone. Determination of the...permutations of the four runs were tried. Table III, then, lends credence to the view that it was the subject’s apprehension at being a "human guinea ... pig " that was responsible for the prolongation of the initial runs and for some of Jhe deviation between duplicates. The experience of Van Liere and

The effect of winter length on duration of dormancy and survival of specialized herbivorous Rhagoletis fruit flies from high elevation environments with acyclic climatic variability.

PubMed

Rull, J; Tadeo, E; Lasa, R; Aluja, M

2017-09-19

Dormancy can be defined as a state of suppressed development allowing insects to cope with adverse conditions and plant phenology. Among specialized herbivorous insects exploiting seasonal resources, diapause frequently evolves as a strategy to adjust to predictable plant seasonal cycles. To cope with acyclic and unpredictable climatic events, it has been found for some insects that a proportion of the population undergoes prolonged dormancy. We compared the response of three species in the Rhagoletis cingulata species group exploiting plants differing in fruiting phenology from environments varying in frequency and timing of acyclic climatic catastrophic events (frost during flowering and fruit set) and varying also in the time of the onset of the rainy season. Small proportions (10 months), and large proportions of pupae died without emerging as adults. The number of days elapsed from the end of artificial winter and adult eclosion was longer for R. cingulata exploiting late fruiting Prunus serotina in Northeastern Mexico than for flies recovered from earlier fruiting plants in the central Altiplano. Rhagoletis turpiniae and northeastern R. cingulata pupae suffered high proportions of parasitism. Large proportions of R. cingulata from central Mexico engaging in prolonged dormancy may be explained by the fact that flowering and fruit set for its host, P. serotina var capuli, driven by the timing of maximum precipitation, matches a period of highest probability of frost often resulting in large areas with fruitless trees at unpredictable time intervals. As a consequence of differences in host plant fruiting phenology, central and northeastern Mexican R. cingulata were found to be allochronically isolated. Prolonged dormancy may have resulted in escape from parasitism.

Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue

PubMed Central

Morley, John W.; Tapson, Jonathan; Breen, Paul P.; van Schaik, André

2016-01-01

Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45–150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6–8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for <4 hrs. These results indicate that long exposure of calcium AM dyes to the intracellular cytoplasm did not alter the intracellular calcium concentration, the functional range of the dye or viability of the neurons. This data extends our previous work showing that a custom recovery chamber can extend the viability of neuronal tissue, and reliable data for both electrophysiology and imaging can be obtained >24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals. PMID:27183102

Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson's disease.

PubMed

Obeso, Ignacio; Wilkinson, Leonora; Rodríguez-Oroz, Maria-Cruz; Obeso, Jose A; Jahanshahi, Marjan

2013-05-01

It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson's disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.

Postantibiotic effect and postantibiotic sub-MIC effect of LTX-109 and mupirocin on Staphylococcus aureus blood isolates.

PubMed

Saravolatz, L D; Pawlak, J; Martin, H; Saravolatz, S; Johnson, L; Wold, H; Husbyn, M; Olsen, W M

2017-11-01

The development of new synthetic antimicrobial peptides like LTX-109 provides a new class of drugs for the treatment of Staphylococcus aureus infections. We evaluated LTX-109 and mupirocin for pharmacodynamic parameters against 10 methicillin-resistant S. aureus isolates. The postantibiotic effect (PAE) is defined as the length of time that bacterial growth is suppressed following a brief exposure to an antibiotic. We also determined the sub-MIC effect (SME) which measures the direct effect of subinhibitory levels on strains that have not previously been exposed to antibiotics. The postantibiotic sub-MIC effect (PA-SME) is a combination of the PAE and SME. LTX-109 had an average PAE of 5·51 h vs 1·04 h for mupirocin. The PA-SME of LTX-109 ranged from 2·51 to 9·33 h as the concentration increased from 0·2 to 0·4 times the minimal inhibitory concentration (MIC). The PA-SME range for mupirocin was 0·93-2·58 h. LTX-109, as compared to mupirocin, demonstrated prolonged time of effect for these pharmacodynamic parameters, which supports persistent activity for several hours after the drug is no longer present or is below the MIC. The pharmacodynamic parameters studied here suggest that LTX-109 is less likely than mupirocin to generate resistance to S. aureus. Resistant bacterial infections continue to be a challenge for clinicians. Identification of antibiotics with pharmacodynamic advantages may be beneficial in the treatment of these infections. An antibiotic with a longer postantibiotic effect may be able to be administered less frequently resulting in improved adherence. In this study, a new synthetic antimicrobial peptide, LTX-109, demonstrated a more prolonged time for LTX-109 than mupirocin against methicillin-resistant Staphylococcus aureus. © 2017 The Society for Applied Microbiology.

Drivers' misjudgement of vigilance state during prolonged monotonous daytime driving.

PubMed

Schmidt, Eike A; Schrauf, Michael; Simon, Michael; Fritzsche, Martin; Buchner, Axel; Kincses, Wilhelm E

2009-09-01

To investigate the effects of monotonous daytime driving on vigilance state and particularly the ability to judge this state, a real road driving study was conducted. To objectively assess vigilance state, performance (auditory reaction time) and physiological measures (EEG: alpha spindle rate, P3 amplitude; ECG: heart rate) were recorded continuously. Drivers judged sleepiness, attention to the driving task and monotony retrospectively every 20 min. Results showed that prolonged daytime driving under monotonous conditions leads to a continuous reduction in vigilance. Towards the end of the drive, drivers reported a subjectively improved vigilance state, which was contrary to the continued decrease in vigilance as indicated by all performance and physiological measures. These findings indicate a lack of self-assessment abilities after approximately 3h of continuous monotonous daytime driving.

Single Doses up to 800 mg of E-52862 Do Not Prolong the QTc Interval – A Retrospective Validation by Pharmacokinetic-Pharmacodynamic Modelling of Electrocardiography Data Utilising the Effects of a Meal on QTc to Demonstrate ECG Assay Sensitivity

PubMed Central

Täubel, Jörg; Ferber, Georg; Lorch, Ulrike; Wang, Duolao; Sust, Mariano; Camm, A. John

2015-01-01

Background E-52862 is a Sigma-1 receptor antagonist (S1RA) currently under investigation as a potential analgesic medicine. We successfully applied a concentration-effect model retrospectively to a four-way crossover Phase I single ascending dose study and utilized the QTc shortening effects of a meal to demonstrate assay sensitivity by establishing the time course effects from baseline in all four periods, independently from any potential drug effects. Methods Thirty two healthy male and female subjects were included in four treatment periods to receive single ascending doses of 500 mg, 600 mg or 800 mg of E-52862 or placebo. PK was linear over the dose range investigated and doses up to 600 mg were well tolerated. The baseline electrocardiography (ECG) measurements on Day-1 were time-matched with ECG and pharmacokinetic (PK) samples on Day 1 (dosing day). Results In this conventional mean change to time-matched placebo analysis, the largest time-matched difference to placebo QTcI was 1.44 ms (90% CI: -4.04, 6.93 ms) for 500 mg; -0.39 ms (90% CI: -3.91, 3.13 ms) for 600 mg and 1.32 ms (90% CI: -1.89, 4.53 ms) for 800 mg of E-52862, thereby showing the absence of any QTc prolonging effect at the doses tested. In addition concentration-effect models, one based on the placebo corrected change from baseline and one for the change of QTcI from average baseline with time as fixed effect were fitted to the data confirming the results of the time course analysis. Conclusion The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a shortening of QTcF of -8.1 (90% CI: -10.4, -5.9) one hour and -7.2 (90% CI: -9.4, -5.0) three hours after a standardised meal. Trial Registration EU Clinical Trials Register EudraCT 2010 020343 13 PMID:26291080

Single Doses up to 800 mg of E-52862 Do Not Prolong the QTc Interval--A Retrospective Validation by Pharmacokinetic-Pharmacodynamic Modelling of Electrocardiography Data Utilising the Effects of a Meal on QTc to Demonstrate ECG Assay Sensitivity.

PubMed

Täubel, Jörg; Ferber, Georg; Lorch, Ulrike; Wang, Duolao; Sust, Mariano; Camm, A John

2015-01-01

E-52862 is a Sigma-1 receptor antagonist (S1RA) currently under investigation as a potential analgesic medicine. We successfully applied a concentration-effect model retrospectively to a four-way crossover Phase I single ascending dose study and utilized the QTc shortening effects of a meal to demonstrate assay sensitivity by establishing the time course effects from baseline in all four periods, independently from any potential drug effects. Thirty two healthy male and female subjects were included in four treatment periods to receive single ascending doses of 500 mg, 600 mg or 800 mg of E-52862 or placebo. PK was linear over the dose range investigated and doses up to 600 mg were well tolerated. The baseline electrocardiography (ECG) measurements on Day-1 were time-matched with ECG and pharmacokinetic (PK) samples on Day 1 (dosing day). In this conventional mean change to time-matched placebo analysis, the largest time-matched difference to placebo QTcI was 1.44 ms (90% CI: -4.04, 6.93 ms) for 500 mg; -0.39 ms (90% CI: -3.91, 3.13 ms) for 600 mg and 1.32 ms (90% CI: -1.89, 4.53 ms) for 800 mg of E-52862, thereby showing the absence of any QTc prolonging effect at the doses tested. In addition concentration-effect models, one based on the placebo corrected change from baseline and one for the change of QTcI from average baseline with time as fixed effect were fitted to the data confirming the results of the time course analysis. The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a shortening of QTcF of -8.1 (90% CI: -10.4, -5.9) one hour and -7.2 (90% CI: -9.4, -5.0) three hours after a standardised meal. EU Clinical Trials Register EudraCT 2010 020343 13.

Effects Of Exercise During Bed Rest

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Bernauer, Edmund M.

1993-01-01

Pair of reports adds to growing body of knowledge of physical deconditioning caused by prolonged bed rest and effectiveness of various exercise regimens in preserving or restoring fitness. Major objective to determine what regimens to prescribe to astronauts before flight, during prolonged weightlessness, and immediately before returning to Earth. Knowledge also benefits patients confined by illness or injury. First report discusses experiment on effects of two types of periodic, intense, short-duration exercise during bed rest. Experiment also discussed in documents "Effects Of Exercise During Prolonged Bed Rest" (ARC-12190), and "Isotonic And Isokinetic Exercise During Bed Rest" (ARC-12180). Second report reviews knowledge acquired with view toward development of protocols for exercise regimens.

Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards.

PubMed

Miyazaki, Kayoko W; Miyazaki, Katsuhiko; Tanaka, Kenji F; Yamanaka, Akihiro; Takahashi, Aki; Tabuchi, Sawako; Doya, Kenji

2014-09-08

Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals' patience to wait for a delayed reward. Copyright © 2014 Elsevier Ltd. All rights reserved.

Involvement of central opioid systems in human interferon-α induced immobility in the mouse forced swimming test

PubMed Central

Makino, Mitsuhiro; Kitano, Yutaka; Komiyama, Chika; Hirohashi, Masaaki; Takasuna, Kiyoshi

2000-01-01

We investigated the mechanism by which human interferon-α (IFN-α) increases the immobility time in a forced swimming test, an animal model of depression.Central administration of IFN-α (0.05–50 IU per mouse, i.cist.) increased the immobility time in the forced swimming test in mice in a dose-dependent manner.Neither IFN-β nor -γ possessed any effect under the same experimental conditions.Pre-treatment with an opioid receptor antagonist, naloxone (1 mg kg−1, s.c.) inhibited the prolonged immobility time induced by IFN-α (60 KIU kg−1, i.v. or 50 IU per mouse. i.cist.).Peripheral administration of naloxone methiodide (1 mg kg−1, s.c.), which does not pass the blood–brain barrier, failed to block the effect of IFN-α, while intracisternal administration of naloxone methiodide (1 nmol per mouse) completely blocked.The effect of IFN-α was inhibited by a μ1-specific opioid receptor antagonist, naloxonazine (35 mg kg−1, s.c.) and a μ1/μ2 receptor antagonist, β-FNA (40 mg kg−1, s.c.). A selective δ-opioid receptor antagonist, naltrindole (3 mg kg−1, s.c.) and a κ-opioid receptor antagonist, nor-binaltorphimine (20 mg kg−1, s.c.), both failed to inhibit the increasing effect of IFN-α.These results suggest that the activator of the central opioid receptors of the μ1-subtype might be related to the prolonged immobility time of IFN-α, but δ and κ-opioid receptors most likely are not involved. PMID:10903965

Acute glucoregulatory and vascular outcomes of three strategies for interrupting prolonged sitting time in postmenopausal women: A pilot, laboratory-based, randomized, controlled, 4-condition, 4-period crossover trial.

PubMed

Kerr, Jacqueline; Crist, Katie; Vital, Daniela G; Dillon, Lindsay; Aden, Sabrina A; Trivedi, Minaxi; Castellanos, Luis R; Godbole, Suneeta; Li, Hongying; Allison, Matthew A; Khemlina, Galina L; Takemoto, Michelle L; Schenk, Simon; Sallis, James F; Grace, Megan; Dunstan, David W; Natarajan, Loki; LaCroix, Andrea Z; Sears, Dorothy D

2017-01-01

Prolonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most) is unclear. In preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a) 2 minutes standing every 20 minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD). Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models) were used to test statistical significance within the small sample size. Nine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal compared to the first meal (i.e., condition-matched 2-hour post-lunch glucose iAUC was lower than 2-hour post-breakfast glucose iAUC) that withstood Bonferroni correction (p = 0.0024 and p = 0.0084, respectively). Using allometrically scaled data, the 10-minute standing every hour condition resulted in an improved FMD response, which was significantly greater than the control condition after Bonferroni correction (p = 0.0033). This study suggests that brief interruptions in prolonged sitting time have modality-specific glucoregulatory and vascular benefits and are feasible in an older adult population. Larger laboratory and real-world intervention studies of pragmatic and effective methods to change sitting habits are needed. ClinicalTrials.gov NCT02743286.

Improvement of the Mechanical Properties of 1022 Carbon Steel Coil by Using the Taguchi Method to Optimize Spheroidized Annealing Conditions.

PubMed

Yang, Chih-Cheng; Liu, Chang-Lun

2016-08-12

Cold forging is often applied in the fastener industry. Wires in coil form are used as semi-finished products for the production of billets. This process usually requires preliminarily drawing wire coil in order to reduce the diameter of products. The wire usually has to be annealed to improve its cold formability. The quality of spheroidizing annealed wire affects the forming quality of screws. In the fastener industry, most companies use a subcritical process for spheroidized annealing. Various parameters affect the spheroidized annealing quality of steel wire, such as the spheroidized annealing temperature, prolonged heating time, furnace cooling time and flow rate of nitrogen (protective atmosphere). The effects of the spheroidized annealing parameters affect the quality characteristics of steel wire, such as the tensile strength and hardness. A series of experimental tests on AISI 1022 low carbon steel wire are carried out and the Taguchi method is used to obtain optimum spheroidized annealing conditions to improve the mechanical properties of steel wires for cold forming. The results show that the spheroidized annealing temperature and prolonged heating time have the greatest effect on the mechanical properties of steel wires. A comparison between the results obtained using the optimum spheroidizing conditions and the measures using the original settings shows the new spheroidizing parameter settings effectively improve the performance measures over their value at the original settings. The results presented in this paper could be used as a reference for wire manufacturers.

Design and characterization of Amoitone B-loaded nanostructured lipid carriers for controlled drug release.

PubMed

Luan, Jingjing; Zhang, Dianrui; Hao, Leilei; Li, Caiyun; Qi, Lisi; Guo, Hejian; Liu, Xinquan; Zhang, Qiang

2013-11-01

Amoitone B, a novel compound chemically synthesized as the analogue of cytosporone B, has been proved to own superior affinity with Nur77 than its parent compound and exhibit notable anticancer activity. However, its application is seriously restricted due to the water-insolubility and short biological half-time. The aim of this study was to construct an effective delivery system for Amoitone B to realize sustained release, thus prolong drug circulation time in body and improve the bioavailability. Nanostructured lipid carriers (NLC) act as a new type of colloidal drug delivery system, which offer the advantages of improved drug loading and sustained release. Amoitone B-loaded NLC (AmB-NLC) containing glyceryl monostearate (GMS) and various amounts of medium chain triglycerides (MCT) were successfully prepared by emulsion-evaporation and low temperature-solidification technology with a particle size of about 200 nm and a zeta potential value of about -20 mV. The results of X-ray diffraction and DSC analysis showed amorphous crystalline state of Amoitone B in NLC. Furthermore, the drug entrapment efficacy (EE) was improved compared with solid lipid nanoparticles (SLN). The EE range was from 71.1% to 84.7%, enhanced with the increase of liquid lipid. In vitro drug release studies revealed biphasic drug release patterns with burst release initially and prolonged release afterwards and the release was accelerated with augment of liquid lipid. These results demonstrated that AmB-NLC could be a promising delivery system to control drug release and improve loading capacity, thus prolong drug action time in body and enhance the bioavailability.

Effect of a novel two-desk sit-to-stand workplace (ACTIVE OFFICE) on sitting time, performance and physiological parameters: protocol for a randomized control trial.

PubMed

Schwartz, Bernhard; Kapellusch, Jay M; Schrempf, Andreas; Probst, Kathrin; Haller, Michael; Baca, Arnold

2016-07-15

Prolonged sitting is ubiquitous in modern society and linked to several diseases. Height-adjustable desks are being used to decrease worksite based sitting time (ST). Single-desk sit-to-stand workplaces exhibit small ST reduction potential and short-term loss in performance. The aim of this paper is to report the study design and methodology of an ACTIVE OFFICE trial. The study was a 1-year three-arm, randomized controlled trial in 18 healthy Austrian office workers. Allocation was done via a regional health insurance, with data collection during Jan 2014 - March 2015. Participants were allocated to either an intervention or control group. Intervention group subjects were provided with traditional or two-desk sit-to-stand workstations in either the first or the second half of the study, while control subjects did not experience any changes during the whole study duration. Sitting time and physical activity (IPAQ-long), cognitive performance (text editing task, Stroop-test, d2R test of attention), workload perception (NASA-TLX) and physiological parameters (salivary cortisol, heartrate variability and body weight) were measured pre- and post-intervention (23 weeks after baseline) for intervention and control periods. Postural changes and sitting/standing time (software logger) were recorded at the workplace for the whole intervention period. This study evaluates the effects of a novel two-desk sit-to-stand workplace on sitting time, physical parameters and work performance of healthy office based workers. If the intervention proves effective, it has a great potential to be implemented in regular workplaces to reduce diseases related to prolonged sitting. ClinicalTrials.gov Identifier: NCT02825303 , July 2016 (retrospectively registered).

Risk factors of prolonged mechanical ventilation following open heart surgery: what has changed over the last decade?

PubMed

Siddiqui, Muhammad-Mujtaba Ali; Paras, Iftikhar; Jalal, Anjum

2012-09-01

To identify the risk factors for prolonged invasive mechanical ventilation after open heart surgery in Pakistan. This study is based on retrospective analysis of database. We conducted study of all patients who underwent open heart surgery at CPE Institute of Cardiology, Multan from March 2009 to May 2011. The data was retrieved from the database in the form of electronic spreadsheet which was then analyzed using SPSS software. The patients with incomplete data entries were removed from the analysis resulting in a set of 1,617 patients. The data of each patient consisted of 65 preoperative, operative and postoperative variables. The data was summarized as means, medians and standard deviations for numeric variables and frequencies and percentages or categoric variables. These risk factors were compared using Chi-sqaure test. Their ODDs ratios and 95% confidence intervals of ODD's Ratios and P values were calculated. Out of a total of 1,617 patients, 77 patients (4.76%) had prolonged ventilation for a cumulated duration of more than over 24 hours. Preoperative renal failure, emphysema, low EF (<30%), urgent operation, preoperative critical state, prolonged bypass time, prolonged cross clamp time, complex surgical procedures and peri-operative myocardial infarction were found to be risk factors for PIMV. Old age, female gender, advanced ASA class, advanced NYHA class, diabetes mellitus, smoking, history of COPD, redo surgery, left main stenosis, obesity and use of intra-aortic balloon pump were not found to have significant ODDs ratios for PIMV. The patients with prolonged ventilation had significantly high mortality i.e. 32.47% while the normal ventilation group had 0.32% overall mortality. Many of the previously considered risk factors for prolonged ventilation after open heart study are no more significant risk factors. However, prolonged ventilation continues to be associated with very high mortality.

A clinical prediction model for prolonged air leak after pulmonary resection.

PubMed

Attaar, Adam; Winger, Daniel G; Luketich, James D; Schuchert, Matthew J; Sarkaria, Inderpal S; Christie, Neil A; Nason, Katie S

2017-03-01

Prolonged air leak increases costs and worsens outcomes after pulmonary resection. We aimed to develop a clinical prediction tool for prolonged air leak using pretreatment and intraoperative variables. Patients who underwent pulmonary resection for lung cancer/nodules (from January 2009 to June 2014) were stratified by prolonged parenchymal air leak (>5 days). Using backward stepwise logistic regression with bootstrap resampling for internal validation, candidate variables were identified and a nomogram risk calculator was developed. A total of 2317 patients underwent pulmonary resection for lung cancer/nodules. Prolonged air leak (8.6%, n = 200) was associated with significantly longer hospital stay (median 10 vs 4 days; P < .001). Final model variables associated with increased risk included low percent forced expiratory volume in 1 second, smoking history, bilobectomy, higher annual surgeon caseload, previous chest surgery, Zubrod score >2, and interaction terms for right-sided thoracotomy and wedge resection by thoracotomy. Wedge resection, higher body mass index, and unmeasured percent forced expiratory volume in 1 second were protective. Derived nomogram discriminatory accuracy was 76% (95% confidence interval [CI], 0.72-0.79) and facilitated patient stratification into low-, intermediate- and high-risk groups with monotonic increase in observed prolonged air leaks (2.0%, 8.9%, and 19.2%, respectively; P < .001). Patients at intermediate and high risk were 4.80 times (95% CI, 2.86-8.07) and 11.86 times (95% CI, 7.21-19.52) more likely to have prolonged air leak compared with patients at low risk. Using readily available candidate variables, our nomogram predicts increasing risk of prolonged air leak with good discriminatory ability. Risk stratification can support surgical decision making, and help initiate proactive, patient-specific surgical management. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

The Role of the CD39/CD73 Purinergic Pathway in Modulating Arterial Thrombosis in Mice

PubMed Central

Covarrubias, R; Chepurko, E; Reynolds, A; Huttinger, ZM; Huttinger, R; Stanfill, K; Wheeler, DG; Novitskaya, T; Robson, SC; Dwyer, KM; Cowan, PJ; Gumina, RJ

2016-01-01

Objective Circulating blood cells and endothelial cells express Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5’-nucleotidase (CD73). CD39 hydrolyzes extracellular ATP or ADP to AMP. CD73 hydrolyzes AMP to adenosine. The goal of this study was to examine the interplay between CD39 and CD73 cascade in arterial thrombosis. Approach and Results To determine how CD73 activity influences in vivo thrombosis, the time to FeCl3-induced arterial thrombosis was measured in CD73-null mice. In response to 5% FeCl3, but not to 10% FeCl3, there was a significant decrease in the time to thrombosis in CD73-null mice compared to wild-type (WT) mice. In mice overexpressing CD39, ablation of CD73 did not inhibit the prolongation in the time to thrombosis conveyed by CD39 overexpression. However, the CD73 inhibitor α-β-methylene-ADP nullified the prolongation in the time to thrombosis in hC39-Tg/CD73-null mice. To determine if hematopoietic-derived cells or endothelial cell CD39 activity regulates in vivo arterial thrombus, bone marrow transplant studies were conducted. FeCl3-induced arterial thrombosis in chimeric mice revealed a significant prolongation in the time to thrombosis in hCD39-Tg reconstituted WT mice, but not on WT reconstituted hCD39-Tg mice. Monocyte depletion with clodronate-loaded liposomes normalized the time to thrombosis in hCD39-Tg mice compared to hCD39-Tg mice treated with control liposomes, demonstrating that increased CD39 expression on monocytes protects against thrombosis. Conclusions These data demonstrate that ablation of CD73 minimally effects in vivo thrombosis, but increased CD39 expression on hematopoietic-derived cells, especially monocytes, attenuates in vivo arterial thrombosis. PMID:27417582

Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

PubMed

Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

2016-08-01

Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The use of tracheostomy speaking valves in mechanically ventilated patients results in improved communication and does not prolong ventilation time in cardiothoracic intensive care unit patients.

PubMed

Sutt, Anna-Liisa; Cornwell, Petrea; Mullany, Daniel; Kinneally, Toni; Fraser, John F

2015-06-01

The aim of this study was to assess the effect of the introduction of in-line tracheostomy speaking valves (SVs) on duration of mechanical ventilation and time to verbal communication in patients requiring tracheostomy for prolonged mechanical ventilation in a predominantly cardiothoracic intensive care unit (ICU). We performed a retrospective preobservational-postobservational study using data from the ICU clinical information system and medical record. Extracted data included demographics, diagnoses and disease severity, mechanical ventilation requirements, and details on verbal communication and oral intake. Data were collected on 129 patients. Mean age was 59 ± 16 years, with 75% male. Demographics, case mix, and median time from intubation to tracheostomy (6 days preimplementation-postimplementation) were unchanged between timepoints. A significant decrease in time from tracheostomy to establishing verbal communication was observed (18 days preimplementation and 9 days postimplementation, P <.05). There was no difference in length of mechanical ventilation (20 days preimplementation-post) or time to decannulation (14 days preimplementation-postimplementation). No adverse events were documented in relation to the introduction of in-line SVs. In-line SVs were successfully implemented in mechanically ventilated tracheostomized patient population. This resulted in earlier verbal communication, no detrimental effect on ventilator weaning times, and no change in decannulation times. The purpose of the study was to compare tracheostomy outcomes in mechanically ventilated patients in a cardiothoracic ICU preintroduction and postintroduction of in-line SVs. It was hypothesized that in-line SVs would improve communication and swallowing specific outcomes with no increase in average time to decannulation or the number of adverse events. Copyright © 2015 Elsevier Inc. All rights reserved.

Hydroelectrolytic and hormonal modifications related to prolonged bedrest in antiorthostatic position

NASA Astrophysics Data System (ADS)

Güell, A.; Dupui, Ph.; Fanjaud, G.; Bes, A.; Moatti, J. P.; Gharrib, Cl.

The effects of prolonged bedrest in antiorthostatic position (-4° head down) on electrolyte balance were studied in 4 young volunteers. An increase was noted in sodium excretion during the first 4 days. Plasma renin activity and plasma aldosterone varied in parallel manner during the same period. Potassium balance and creatinine clearance were not significantly modified. In light of these data we feel that prolonged bedrest in antiorthostatic position constitutes an effective way to simulate on earth metabolic and hormonal modifications occurring in man under weightlessness conditions.

Effect of prolonged bed rest on lung volume in normal individuals

NASA Technical Reports Server (NTRS)

Beckett, W. S.; Vroman, N. B.; Nigro, D.; Thompson-Gorman, S.; Wilkerson, J. E.

1986-01-01

The effect of prolonged bed rest on the lung function was studied by measuring forced vital capacity (FVC) and total lung capacity (TLC) in normal subjects before, during, and after 11- to 12-day rest periods. It was found that both FVC and TLC increased during bed rest (compared with the ambulatory controls), while residual volume and functional residual capacity of the respiratory system did not change. It is concluded that the increase in TLC by prolonged bed rest is not dependent on alterations in plasma volume.

The spatial learning and memory performance in methamphetamine–sensitized and withdrawn rats

PubMed Central

Bigdeli, Imanollah; Asia, Masomeh Nikfarjam- Haft; Miladi-Gorji, Hossein; Fadaei, Atefeh

2015-01-01

Objective(s): There is controversial evidence about the effect of methamphetamine (METH) on spatial memory. We tested the time- dependent effects of METH on spatial short-term (working) and long-term (reference) memory in METH –sensitized and withdrawn rats in the Morris water maze. Materials and Methods: Rats were sensitized to METH (2 mg/kg, daily/5 days, SC). Rats were trained in water maze (4 trials/day/for 5 days). Probe test was performed 24 hr after training. Two days after probe test, working memory training (2 trials/day/for 5 days) was conducted. Acquisition–retention interval was 75 min. The treatment was continued per day 30 and 120 min before the test. Two groups of METH –sensitized rats were trained in reference memory after a longer period of withdrawal (30 days). Results: Sensitized rats exhibited significantly longer escape latencies on the training, spent significantly less time in the target zone (all, P<0.05), and their working memory impaired 30 min after injection. While, METH has no effect on the spatial learning process 120 min after injection, and rats spent significantly less time in the target zone (P<0.05), as well it has no effect on working memory. Also, impairment of reference memory persisted after prolonged abstinence. Conclusion: Our findings indicated that METH impaired spatial learning and memory 30 min after injection, but spared spatial learning, either acquisition or retention of spatial working, but partially impaired retention of spatial reference memory following 120 min after injection in sensitized rats, which persisted even after prolonged abstinence. PMID:25945235

Which population groups are most unaware of CVD risks associated with sitting time?

PubMed

Duncan, Mitch J; Gilson, Nicholas; Vandelanotte, Corneel

2014-08-01

Prolonged sitting is an emerging risk factor for poor health yet few studies have examined awareness of the risks associated with sitting behaviours. This study identifies the population subgroups with the highest levels of unawareness regarding the cardiovascular disease (CVD) risks associated with sitting behaviours. Adults (n=1256) living in Queensland, Australia completed a telephone-based survey in 2011, analysis conducted in 2013. The survey assessed participant's socio-demographic characteristics, physical activity, sitting behaviours and awareness of CVD risks associated with three sitting behaviours: 1) sitting for prolonged periods, 2), sitting for prolonged periods whilst also engaging in regular physical activity, and 3) breaking up periods of prolonged sitting with short activity breaks. Population sub-groups with the highest levels of unawareness were identified based on socio-demographic and behavioural characteristics using signal detection analysis. Unawareness ranged from 23.3% to 67.0%. Age was the most important variable in differentiating awareness levels; younger adults had higher levels of unawareness. Body mass index, physical activity, TV viewing, employment status and time spent at work also identified population sub-groups. Unawareness of CVD risk for prolonged sitting was moderately high overall. Younger adults had high levels of unawareness on all of the outcomes examined. Copyright © 2014 Elsevier Inc. All rights reserved.

QT prolongation and proarrhythmia by moxifloxacin: concordance of preclinical models in relation to clinical outcome

PubMed Central

Chen, Xian; Cass, Jessica D; Bradley, Jenifer A; Dahm, Corinn M; Sun, Zhuoqian; Kadyszewski, Edmund; Engwall, Michael J; Zhou, Jun

2005-01-01

Moxifloxacin, a fluoroquinolone antibiotic associated with QT prolongation, has been recommended as a positive control by regulatory authorities to evaluate the sensitivity of both clinical and preclinical studies to detect small but significant increases in QT interval measurements. In this study, we investigated effects of moxifloxacin on the hERG current in HEK-293 cells, electrocardiograms in conscious telemetered dogs, and repolarization parameters and arrhythmogenic potentials in the arterially perfused rabbit ventricular wedge model. Moxifloxacin inhibited the hERG current with an IC50 of 35.7 μM. In conscious telemetered dogs, moxifloxacin significantly prolonged QTc at 30 and 90 mg kg−1, with mean serum Cmax of 8.52 and 22.3 μg ml−1, respectively. In the wedge preparation, moxifloxacin produced a concentration-dependent prolongation of the action potential duration, QT interval, and the time between peak and end of the T wave, an indicator for transmural dispersion of repolarization. Phase 2 early after-depolarizations were observed in one of five experiments at 30 μM and five of five experiments at 100 μM. The arrhythmogenic potential was also concentration-dependent, and 100 μM (∼18-fold above the typical unbound Cmax exposure in clinical usage) appeared to have a high risk of inducing torsade de pointes (TdP). Our data indicated a good correlation among the concentration–response relationships in the three preclinical models and with the available clinical data. The lack of TdP report by moxifloxacin in patients without other risk factors might be attributable to its well-behaved pharmacokinetic profile and other dose-limiting effects. PMID:16158069

Improving PTSD Outcomes in OIF/OEF Returnees: A Randomized Clinical Trial of Hydrocortisone Augmentation of Prolonged Exposure Therapy

DTIC Science & Technology

2012-08-01

Melissa D . Altman, PhD will ensure that the ratings are accomplished in a reasonable time frame, and make the results available to the PI and co...Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report. European Journal of Traumatology. 2010(1): 5643. d . Solutions to...Brief Assessment of Cognition in Schizophrenia (BACS): Symbol-Coding Category Fluency: Animal Naming Trail Making Test: Part A Timed paper

Quantification of Acute Vocal Fold Epithelial Surface Damage with Increasing Time and Magnitude Doses of Vibration Exposure

PubMed Central

Kojima, Tsuyoshi; Van Deusen, Mark; Jerome, W. Gray; Garrett, C. Gaelyn; Sivasankar, M. Preeti; Novaleski, Carolyn K.; Rousseau, Bernard

2014-01-01

Because the vocal folds undergo repeated trauma during continuous cycles of vibration, the epithelium is routinely susceptible to damage during phonation. Excessive and prolonged vibration exposure is considered a significant predisposing factor in the development of vocal fold pathology. The purpose of the present study was to quantify the extent of epithelial surface damage following increased time and magnitude doses of vibration exposure using an in vivo rabbit phonation model. Forty-five New Zealand white breeder rabbits were randomized to nine groups and received varying phonation time-doses (30, 60, or 120 minutes) and magnitude-doses (control, modal intensity phonation, or raised intensity phonation) of vibration exposure. Scanning electron microscopy and transmission electron microscopy was used to quantify the degree of epithelial surface damage. Results revealed a significant reduction in microprojection density, microprojection height, and depth of the epithelial surface with increasing time and phonation magnitudes doses, signifying increased epithelial surface damage risk with excessive and prolonged vibration exposure. Destruction to the epithelial cell surface may provide significant insight into the disruption of cell function following prolonged vibration exposure. One important goal achieved in the present study was the quantification of epithelial surface damage using objective imaging criteria. These data provide an important foundation for future studies of long-term tissue recovery from excessive and prolonged vibration exposure. PMID:24626217

Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants.

PubMed

Undre, Nasrullah; Dickinson, James

2017-04-04

Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants. A phase 1, open-label, single-dose, cross-over study. A single clinical research unit. In total, 20 male participants, 18-55 years old, entered and completed the study. All participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration-time profile over 144 hours was used to estimate pharmacokinetic parameters. Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration-time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC 0-∞ ); AUC measured until the last quantifiable concentration (AUC 0-tz ); maximum observed concentration (C max ); time to C max (T max )). Tolerability was assessed throughout the study. Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC 0-tz and AUC 0-∞ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). C max was higher for oral and nasogastric suspension (30% and 28%, respectively), and median T max was shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10 mg doses of tacrolimus were well tolerated. Compared with intact capsules, the rate of absorption of prolonged-release tacrolimus from suspension was faster, leading to higher peak blood concentrations and shorter time to peak; relative bioavailability was similar with suspension administered orally. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effect of 10 days of intermittent fasting on Wingate anaerobic power and prolonged high-intensity time-to-exhaustion cycling performance.

PubMed

Naharudin, Mohamed Nashrudin Bin; Yusof, Ashril

2018-06-01

Many physically active individuals have undertaken intermittent fasting to reduce their daily caloric intake. However, abstaining from meals for a specific length of time may lead to the acute disturbance of highly carbohydrate-dependent exercise performance. The purpose of this study was to observe the effect of 10 days of intermittent fasting on high-intensity type exercises, Wingate anaerobic (WT) and prolonged high-intensity time-to-exhaustion (HIT) cycling test. Twenty participants were randomised into an intermittent fasting (FAS) and a control group (CON). One day after baseline data collection on Day-0 where participants consumed their recommended daily caloric intake (FAS = 2500 ± 143 kcal day -1 ; CON = 2492 ± 20 kcal day -1 ) served over a course of five meals, the FAS group consumed only four meals where 40% was restricted by the omission of lunch (FAS = 1500 ± 55 kcal day -1 ). This diet was then continued for 10 days. Data on exercise performance and other dependent variables were collected on Day-2, -4, -6, -8 and -10. A reduction in WT power in the FAS group was observed on Day-2 (821.74 ± 66.07 W) compared to Day-0 (847.63 ± 95.94 W) with a moderate effect size (p < .05, ES = 0.4), while HIT time-to-exhaustion performance declined over the 10 days with a trend of recovery from a large to a minimum effect size (p < .05, ES = 0.8-0.3). Body weight and triglyceride were consistently reduced in the FAS group (p < .01). The present study suggests that intermittent fasting must exceed 10 days to ensure that high-intensity performance does not deteriorate because this length of time seems to be required for effective adaptation to the new dietary regimen.

A comparative study of QT prolongation with serotonin reuptake inhibitors.

PubMed

Ojero-Senard, Ana; Benevent, Justine; Bondon-Guitton, Emmanuelle; Durrieu, Geneviève; Chebane, Leila; Araujo, Melanie; Montastruc, Francois; Montastruc, Jean-Louis

2017-10-01

QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the "suspected" SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD. In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90-3.87]) or escitalopram (2.50 [2.11-2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients. This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.

Modeling Cancer Cell Growth Dynamics In vitro in Response to Antimitotic Drug Treatment

PubMed Central

Lorz, Alexander; Botesteanu, Dana-Adriana; Levy, Doron

2017-01-01

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process. More precisely, our model comprises two age-structured partial differential equations for the proliferative and apoptotic cell compartments and one ordinary differential equation for the quiescent compartment. To reflect the intrinsic cell heterogeneity that governs the growth dynamics, proliferative and apoptotic cells are structured in “age,” i.e., the amount of time remaining to be spent in each respective compartment. In our model, we considered an antimitotic drug whose effect on the cellular dynamics is to induce mitotic arrest, extending the average cell-cycle length. The prolonged mitotic arrest induced by the drug can trigger apoptosis if the time a cell will spend in the cell cycle is greater than the mitotic arrest threshold. We studied the drug’s effect on the long-term cancer cell growth dynamics using different durations of prolonged mitotic arrest induced by the drug. Our numerical simulations suggest that at confluence and in the absence of the drug, quiescence is the long-term asymptotic behavior emerging from the cancer cell growth dynamics. This pattern is maintained in the presence of small increases in the average cell-cycle length. However, intermediate increases in cell-cycle length markedly decrease the total number of cells and can drive the cancer population to extinction. Intriguingly, a large “switch-on/switch-off” increase in the average cell-cycle length maintains an active cell population in the long term, with oscillating numbers of proliferative cells and a relatively constant quiescent cell number. PMID:28913178

Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate.

PubMed

Allam, Ayat; Fetih, Gihan

2016-01-01

The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug's bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06%±13.28%), as compared with that after oral tablet administration (39.37%±11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of metoprolol tartrate.

Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

PubMed Central

Allam, Ayat; Fetih, Gihan

2016-01-01

The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06%±13.28%), as compared with that after oral tablet administration (39.37%±11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of metoprolol tartrate. PMID:27536063

Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo

2014-01-01

Introduction Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. Method 120 individuals with chronic pain were recruited in 4 groups (n=30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M=121 weeks; SD=23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. Results A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (Log rank=15.50; p<.001) and tolerance (Log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p’s<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p’s<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns). Conclusion Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. PMID:25456326

Long-Term Effects of Attentional Performance on Functional Brain Network Topology

PubMed Central

Breckel, Thomas P. K.; Thiel, Christiane M.; Bullmore, Edward T.; Zalesky, Andrew; Patel, Ameera X.; Giessing, Carsten

2013-01-01

Individuals differ in their cognitive resilience. Less resilient people demonstrate a greater tendency to vigilance decrements within sustained attention tasks. We hypothesized that a period of sustained attention is followed by prolonged changes in the organization of “resting state” brain networks and that individual differences in cognitive resilience are related to differences in post-task network reorganization. We compared the topological and spatial properties of brain networks as derived from functional MRI data (N = 20) recorded for 6 mins before and 12 mins after the performance of an attentional task. Furthermore we analysed changes in brain topology during task performance and during the switches between rest and task conditions. The cognitive resilience of each individual was quantified as the rate of increase in response latencies over the 32-minute time course of the attentional paradigm. On average, functional networks measured immediately post-task demonstrated significant and prolonged changes in network organization compared to pre-task networks with higher connectivity strength, more clustering, less efficiency, and shorter distance connections. Individual differences in cognitive resilience were significantly correlated with differences in the degree of recovery of some network parameters. Changes in network measures were still present in less resilient individuals in the second half of the post-task period (i.e. 6–12 mins after task completion), while resilient individuals already demonstrated significant reductions of functional connectivity and clustering towards pre-task levels. During task performance brain topology became more integrated with less clustering and higher global efficiency, but linearly decreased with ongoing time-on-task. We conclude that sustained attentional task performance has prolonged, “hang-over” effects on the organization of post-task resting-state brain networks; and that more cognitively resilient individuals demonstrate faster rates of network recovery following a period of attentional effort. PMID:24040185

Venetoclax does not prolong the QT interval in patients with hematological malignancies: an exposure-response analysis.

PubMed

Freise, Kevin J; Dunbar, Martin; Jones, Aksana K; Hoffman, David; Enschede, Sari L Heitner; Wong, Shekman; Salem, Ahmed Hamed

2016-10-01

Venetoclax (ABT-199/GDC-0199) is a selective first-in-class B cell lymphoma-2 inhibitor being developed for the treatment of hematological malignancies. The aim of this study was to determine the potential of venetoclax to prolong the corrected QT (QTc) interval and to evaluate the relationship between systemic venetoclax concentration and QTc interval. The study population included 176 male and female patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 105) or non-Hodgkin's lymphoma (n = 71) enrolled in a phase 1 safety, pharmacokinetic, and efficacy study. Electrocardiograms were collected in triplicate at time-matched points (2, 4, 6, and 8 h) prior to the first venetoclax administration and after repeated venetoclax administration to achieve steady state conditions. Venetoclax doses ranged from 100 to 1200 mg daily. Plasma venetoclax samples were collected after steady state electrocardiogram measurements. The mean and upper bound of the 2-sided 90 % confidence interval (CI) QTc change from baseline were <5 and <10 ms, respectively, at all time points and doses (<400, 400, and >400 mg). Three subjects had single QTc values >500 ms and/or ΔQTc > 60 ms. The effect of venetoclax concentration on both ΔQTc and QTc was not statistically significant (P > 0.05). At the mean maximum concentrations achieved with therapeutic (400 mg) and supra-therapeutic (1200 mg) venetoclax doses, the estimated drug effects on QTc were 0.137 (90 % CI [-1.01 to 1.28]) and 0.263 (90 % CI [-1.92 to 2.45]) ms, respectively. Venetoclax does not prolong QTc interval even at supra-therapeutic doses, and there is no relationship between venetoclax concentrations and QTc interval.

Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

PubMed

Wachholtz, Amy; Gonzalez, Gerardo

2014-12-01

Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p < .001) and tolerance (log rank = 20.11; p < .001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's < .01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p < .05), with the highest tolerance found among opioid naïve control group participants (p's < .001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R = .37; p < .05); but duration of abstinence did not alter sensitivity (ns). Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Parecoxib added to ropivacaine prolongs duration of axillary brachial plexus blockade and relieves postoperative pain.

PubMed

Liu, Xiaoming; Zhao, Xuan; Lou, Jian; Wang, Yingwei; Shen, Xiaofang

2013-02-01

Cyclooxygenase (COX)-2 antagonist is widely used for intravenous postoperative pain relief. Recent studies reported COX-2 in the spinal dorsal horn could modulate spinal nociceptive processes. Epidural parecoxib in rats showed no neurotoxicity. These findings suggested applying a COX-2 antagonist directly to the central or peripheral nerve might provide better analgesia. We therefore determined: (1) whether the addition of parecoxib to ropivacaine injected locally on the nerve block affected the sensory and motor block times of the brachial plexus nerve block; and (2) whether parecoxib injected locally on the nerve or intravenously had a similar analgesic adjuvant effect. We conducted a randomized controlled trial from January 2009 to November 2010 with 150 patients scheduled for elective forearm surgery, using a multiple-nerve stimulation technique. Patients were randomly allocated into one of three groups: Group A (n = 50) received ropivacaine 0.25% alone on the brachial plexus nerve; Group B (n = 50) received ropivacaine together with 20 mg parecoxib locally on the nerve block; and Group C (n = 50) received 20 mg parecoxib intravenously. We recorded the duration of the sensory and motor blocks, and the most severe pain score during a 24-hour postoperative period. Parecoxib added locally on the nerve block prolonged the motor and sensory block times compared with Group A. However, parecoxib injected intravenously had no such effect. Pain intensity scores in Group B were lower than those in Groups A and C. Parecoxib added to ropivacaine locally on the nerve block prolonged the duration of the axillary brachial plexus blockade and relieved postoperative pain for patients having forearm orthopaedic surgery. Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Evaluation of volatile components from spikenard: valerena-4,7(11)-diene is a highly active sedative compound.

PubMed

Takemoto, Hiroaki; Yagura, Toru; Ito, Michiho

2009-10-01

Valerena-4,7(11)-diene and beta-maaliene were isolated from spikenard for the first time, and the effects of inhaling these compounds were investigated. Both compounds reduced the locomotor activity of mice dose-dependently, even at a low dose. Valerena-4,7(11)-diene had a particularly profound effect, with the strongest sedative activity observed at a dose of 0.06%. Caffeine-treated mice that showed an area under the curve (AUC) for locomotor activity that was double that of controls were calmed to normal levels by administration of valerena-4,7(11)-diene. The continuous sleep time of pentobarbital-treated mice was prolonged by about 2.7 times with valerena-4,7(11)-diene, an effect similar to that of chlorpromazine administered orally.

Prolonged central motor conduction time of lower limb muscle in spinocerebellar ataxia 6.

PubMed

Chen, Jen-Tse; Lin, Yung-Yang; Lee, Yi-Chung; Soong, Bing-Wen; Wu, Zin-An; Liao, Kwong-Kum

2004-05-01

We investigated the function of corticospinal tract in spinocerebellar ataxia 6 (SCA6) by measuring the central motor conduction time (CMCT). Motor evoked potentials (MEP) of tibialis anterior (TA) muscle were elicited by magnetic stimulation to motor cortex and spinal cord in 9 SCA6 patients and 10 normal height- and age-matched subjects. CMCT in lower limb of SCA6 patients (18.1+/-1.9 ms) was significantly prolonged than that of the normal subjects (15.0+/-1.0 ms) ((p < 0.001). The prolonged CMCT was well correlated with the duration of disease (p = 0.005), but MEP amplitudes and stimulation intensities were not significantly different. These results indicate that the corticospinal tract function is also impaired and correlate with the disease duration in SCA6.

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

PubMed

Kui, Péter; Orosz, Szabolcs; Takács, Hedvig; Sarusi, Annamária; Csík, Norbert; Rárosi, Ferenc; Csekő, Csongor; Varró, András; Papp, Julius Gy; Forster, Tamás; Farkas, Attila S; Farkas, András

2016-01-01

Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of perfluorinated amphiphiles on backward swimming in Paramecium caudatum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsubara, Eriko; Harada, Kouji; Research Fellow of the Japan Society for the Promotion of Science, Tokyo 1028472

2006-01-13

PFOS and PFOA are ubiquitous contaminants in the environment. We investigated the effects of fluorochemicals on calcium currents in Paramecium caudatum using its behavioral changes. Negatively charged amphiphiles prolonged backward swimming (BWS) of Paramecium. PFOS significantly prolonged BWS, while PFOA was less potent (EC{sub 5}: 29.8 {+-} 4.1 and 424.1 {+-} 124.0 {mu}M, respectively). The BWS prolongation was blocked by cadmium, indicating that the cellular calcium conductance had been modified. The positively charged amphiphile FOSAPrTMA shortened BWS (EC{sub 5}: 19.1 {+-} 17.3). Nonionic amphiphiles did not affect BWS. The longer-chain perfluorinated carboxylates PFNA and PFDA were more potent than PFOAmore » (EC{sub 5}: 98.7 {+-} 20.1 and 60.4 {+-} 10.1 {mu}M, respectively). However, 1,8-perfluorooctanedioic acid and 1,10-perfluorodecanedioic acid did not prolong BWS. The critical micelle concentration (CMC) and BWS prolongation for negatively charged amphiphiles showed a clear correlation (r {sup 2} = 0.8008, p < 0.001). In summary, several perfluorochemicals and PFOS and PFOA had similar effects in Paramecium, while chain length, CMC, and electric charge were major determinants of BWS duration.« less

Effect of prolonged heating on the asphalt-aggregate bond strength of HMA containing liquid anti-strip additives

DOT National Transportation Integrated Search

2008-09-01

In this study, an attempt was made to determine the effect of prolonged heating on the bond strength between : aggregate and asphalt that contained anti-strip additives (LOF 6500 and Morelife 2200). On account of the : substantial decrease of anti-st...

Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft

PubMed Central

Qiu, Ying; Yun, Mark M; Han, Xia; Zhao, Ruidong; Zhou, Erxia; Yun, Sheng

2014-01-01

Background: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. Methods: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. Results: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. Conclusions: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID:25126177

Nutrient changes and antinutrient contents of beniseed and beniseed soup during cooking using a Nigerian traditional method.

PubMed

Agiang, M A; Umoh, I B; Essien, A I; Eteng, M U

2010-10-15

Evaluations of the effect of prolong cooking on the nutrient and antinutrient composition ofbeniseed and beniseed soup were carried out in this study. Proximate, mineral, vitamin A and C and antinutrient compositions of raw beniseed (BS-R), beniseed boiled (BSB) for 15, 30, 45 and 60 min and beniseed soup (BSS) cooked for the same intervals of time were assessed. Results of the proximate composition analyses showed that raw and boiled beniseed had lower moisture content (5.39-5.51%) than beniseed soups (10.06-15.20%). Nitrogen-free extract (total carbohydrates), fats and phosphorus contents were improved in both the boiled beniseed and beniseed soup while calcium and potassium were increased in the boiled seeds and soup samples respectively. Moisture (in the raw and boiled beniseed), ash, magnesium, zinc, iron contents in both the seed and soup were unchanged in all the samples. Vitamins A and C levels of both boiled beniseed and beniseed soup samples were reduced with increase in cooking time. Beniseed soup had higher protein contents than both the raw and boiled beniseed which decreased with increase in cooking time. Beniseed samples provided good sources of energy (572.97-666.05 kcal/100 g). Except for phytate, the levels of antinutrients tested were lower in the raw and boiled beniseed than in the soup samples which decreased with increase in cooking time. The results are discussed with reference to the effect of prolonged cooking on the nutrient requirements of consumers.

Mortality and morphological anomalies related to the passage of cosmic heavy ions through the smallest flowering aquatic plant wolffia arrhiza

NASA Astrophysics Data System (ADS)

Facius, R.; Scherer, K.; Strauch, W.; Nevzgodina, L. V.; Maximova, E. N.; Akatov, Yu. A.

Radiobiological effects of single cosmic heavy ions on individual, actively metabolizing test organisms, plants of Wolffia arrhiza, have been explored in an experiment flown aboard the Russian Biosatellite 10. Mortality induced during space flight, population dynamics during subsequent cultivation, and morphological anomalies occurring in the plants of these cultures were investigated. Correlation of these effects with the passage of a heavy ion was achieved by inserting monolayers of plants in a stack of surrounding plastic nuclear track detectors (BIOSTACK). Enhanced initial mortality and delayed decline of induced anomalies have been significantly associated with the passage of single heavy ions, in particular if ions penetrated the budding region of the plants. The prolonged persistence of anomalies in filial generations as an indication of delayed genetic damage has been detected for the first time as the consequence of the hit by a single heavy ion. Regarding radiation protection of space crew during prolonged missions, especially outside the magnetosphere, this appears to be a significant finding.

Trials of Improved Practices (TIPs): A Strategy for Making Long-Lasting Nets Last Longer?

PubMed Central

Harvey, Steven A.; Paredes Olórtegui, Maribel; Leontsini, Elli; Ramal Asayag, César; Scott, Kerry; Winch, Peter J.

2013-01-01

Long-lasting insecticidal net (LLIN) use is a proven malaria prevention method. Mass distribution has greatly expanded LLIN access in sub-Saharan Africa, but a gap remains between LLIN ownership and use. Furthermore, LLINs wear out more quickly than anticipated. This paper suggests a participatory research strategy—trials of improved practices (TIPs)—that could identify locally appropriate approaches to prolonging net life and increasing effective use. We used TIPs to overcome barriers to optimal net use in the Peruvian Amazon. Working with 15 families in three villages, we tested home treatment of cotton nets, use of an alternative netting fabric, and alternative washing and care instructions. TIPs helped confirm feasibility of these interventions. Although our findings are time- and context-specific, TIPs could help improve consistency and effectiveness of current LLIN use and prolong net lifespan in sub-Saharan Africa and elsewhere. This would help maximize the value of shrinking donor resources for malaria. PMID:23530074

Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide.

PubMed

Vandamme, Th F; Brobeck, L

2005-01-20

The purpose of this study was to determine the influence of a controlled incremental increase in size, molecular weight and number of amine, carboxylate and hydroxyl surface groups in several series of poly(amidoamine) (PAMAM) dendrimers for controlled ocular drug delivery. The duration of residence time was evaluated after solubilization of several series of PAMAM dendrimers (generations 1.5 and 2-3.5 and 4) in buffered phosphate solutions containing 2 per thousand (w/v) of fluorescein. The New Zealand albino rabbit was used as an in vivo model for qualitative and quantitative assessment of ocular tolerance and retention time after a single application of 25 microl of dendrimer solution to the eye. The same model was also used to determine the prolonged miotic or mydriatic activities of dendrimer solutions, some containing pilocarpine nitrate and some tropicamide, respectively. Residence time was longer for the solutions containing dendrimers with carboxylic and hydroxyl surface groups. No prolongation of remanence time was observed when dendrimer concentration (0.25-2%) increased. The remanence time of PAMAM dendrimer solutions on the cornea showed size and molecular weight dependency. This study allowed novel macromolecular carriers to be designed with prolonged drug residence time for the ophthalmic route.

Application of edible coating with essential oil in food preservation.

PubMed

Ju, Jian; Xie, Yunfei; Guo, Yahui; Cheng, Yuliang; Qian, He; Yao, Weirong

2018-03-26

Compared with other types of packaging, edible coatings are becoming more and more popular because of their more environmentally friendly properties and active ingredients carrying ability. The edible coating can reduce the influence of essential oils (EOs) on the flavor of the product and also can prolong the action time of EOs through the slow-release effect, which effectively promote the application of EOs in food. Understanding the different combinations of edible coatings and EOs as well as their antimicrobial effects on different microorganisms will be more powerful and targeted to promote the application of EOs in real food systems. The review focus on the contribution of the combination of EOs and edible coatings (EO-edible coatings) to prolong the shelf life of food products, (1) specifically addressing the main materials used in the preparation of EO-edible coatings and the application of EO-edible coatings in the product, (2) systematically summarizing the main production method of EO-edible coatings, (3) discussing the antiseptic activity of EO-edible coatings on different microorganisms in food.

Exercise as a countermeasure for physiological adaptation to prolonged spaceflight

NASA Technical Reports Server (NTRS)

Convertino, V. A.

1996-01-01

Exercise represents the primary countermeasure used during spaceflight to maintain or restore maximal aerobic capacity (VO2max), musculoskeletal structure, and orthostatic function. However, no single exercise or combination of prescriptions has proven entirely effective in restoring cardiovascular and musculoskeletal functions to preflight levels following prolonged spaceflight. As human spaceflight exposures increase in duration, assessment and development of various effective exercise-based protective procedures become paramount. This must involve improvement in specific countermeasure prescription as well as development of additional approaches that will allow space travelers greater flexibility and medical safety during long flights. Effective exercise prescription will be based on identification of basic physiological stimuli that maintain normal function in terrestrial gravity and understanding of how specific combinations of exercise characteristics e.g., duration, frequency, intensity, mode) can mimic these stimuli and affect the overall process of adaptation to microgravity. This can be accomplished only with greater emphasis of research on ground-based experiments. Future attention must be directed to improving exercise compliance while minimizing both crew time and the impact of the exercise on life-support resources.

Preparation and optimization of chlorophene-loaded nanospheres as controlled release antimicrobial delivery systems.

PubMed

Phuengkham, Hathaichanok; Teeranachaideekul, Veerawat; Chulasiri, Malyn; Nasongkla, Norased

2016-01-01

Chlorophene-loaded nanospheres with various formulation parameters were evaluated. The optimal formulation was found at 0.1% w/v of poloxamer 407, 15 mL of ethyl acetate and 20% initial chlorophene loading that provided the suitable size (179 nm), the highest loading content (19.2%), encapsulation efficiency (88.0%) and yield (91.6%). Moreover, encapsulation of chlorophene in nanospheres was able to prolong and sustain drug release over one month. Chlorophene-loaded nanospheres were effective against Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans), the main cause of hospital-acquired infections. Chlorophene-loaded nanospheres were effective against S. aureus (>46 µg/mL) and C. albicans (>184 µg/mL). These nanospheres appeared to have profound effect on the time-dependent hemolytic activity due to gradual release of chlorophene. At the concentration of 46 µg/mL, nearly no HRBC hemolysis in 24 h compared to 80% of hemolysis from free drug. In conclusion, polymeric nanospheres were successfully fabricated to encapsulate chlorophene which can eliminate inherent toxicity of drugs and have potential uses in prolonged release of antimicrobial.

Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development

PubMed Central

Salvi, Vaibhav; Karnad, Dilip R; Panicker, Gopi Krishna; Kothari, Snehal

2010-01-01

Following reports of death from cardiac arrhythmias with drugs like terfenadine and cisapride, the International Conference for Harmonization formulated a guidance (E14) document. This specifies that all new drugs must undergo a ‘thorough QT/QTc’ (TQT) study to detect drug-induced QT prolongation, a surrogate marker of ventricular tachycardia, especially torsades de pointes (TdPs). With better understanding of data from several completed TQT studies, regulatory requirements have undergone some changes since the E14 guidance was implemented in October 2005. This article reviews the implications of the E14 guidance and the changes in its interpretation including choice of baseline QT, demonstration of assay sensitivity, statistical analysis of the effect of new drug and positive control, and PK-PD modelling. Some issues like use of automated QT measurements remain unresolved. Pharmaceutical companies too are modifying Phase 1 studies to detect QTc liability early in order to save time and resources. After the E14 guidance, development of several drugs that prolong QTc by >5 ms is being abandoned by sponsors. However, all drugs that prolong the QT interval do not increase risk of TdP. Researchers in regulatory agencies, academia and industry are working to find better biomarkers of drug-induced TdP which could prevent many useful drugs from being prematurely abandoned. Drug-induced TdP is a rare occurrence. With fewer drugs that prolong QT interval reaching the licensing stage, knowing which of these drugs are torsadogenic is proving to be elusive. Thus, paradoxically, the effectiveness of the E14 guidance itself has made prospective validation of new biomarkers difficult. This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 PMID:19775279

Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation.

PubMed

Nidhi, Malviya; Patro, M Nagaraju; Kusumvalli, Somisetty; Kusumdevi, Vemula

2016-01-01

Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion-evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box-Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN "S8" were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in C max and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized.

Duration of labor and the risk of severe postpartum hemorrhage: A case-control study

PubMed Central

Stray-Pedersen, Babill; Forsén, Lisa; Vangen, Siri

2017-01-01

Objective Our main objective was to investigate the association between duration of active labor and severe postpartum hemorrhage. We examined the effect of the total duration of active labor, the effect of each stage of active labor, and the gradient effect of duration of labor on severe postpartum hemorrhage. Methods A case-control study was generated from a source population of all women admitted for delivery at Oslo University Hospital and Drammen Hospital in Buskerud municipality during the time period January 1, 2008 to December 31, 2011. The study population included all cases of severe postpartum hemorrhage (n = 859) and a random sample of controls (n = 1755). Severe postpartum hemorrhage was defined as postpartum blood loss ≥1500 mL or need for blood transfusion. Prolonged labor was defined as duration of active labor >12 hours according to the definition of the World Health Organization. We used logistic multivariable regression in the analysis. Results We observed a significantly longer mean duration of labor in women who experienced severe postpartum hemorrhage compared to controls (5.4 versus 3.8 hours, p<0.001). Women with severe postpartum hemorrhage also had a longer duration of all stages of active labor compared to controls. The association between the duration of active labor and severe postpartum changed from a linear dose-response association to a threshold association after adjusting for augmentation with oxytocin, induction of labor, primiparity, and fever during labor. Compared to controls, women with severe postpartum hemorrhage were more likely to have a prolonged labor >12 hours (adjusted odds ratio = 2.44, 95% confidence interval: 1.69–3.53, p< 0.001). Conclusion Prolonged active labor (duration >12 hours) was associated with severe postpartum hemorrhage. Increased vigilance seems required when the labor is prolonged to reduce the risk of severe postpartum hemorrhage. PMID:28384337

More Attention to Attention? An Eye-Tracking Investigation of Selection of Perceptual Attributes during a Task Switch

ERIC Educational Resources Information Center

Longman, Cai S.; Lavric, Aureliu; Monsell, Stephen

2013-01-01

Switching tasks prolongs response times, an effect reduced but not eliminated by active preparation. To explore the role of attentional selection of the relevant stimulus attribute in these task-switch costs, we measured eye fixations in participants cued to identify either a face or a letter displayed on its forehead. With only 200 ms between cue…

Cognitive Sciences

NASA Technical Reports Server (NTRS)

1997-01-01

Session MP4 includes short reports on: (1) Face Recognition in Microgravity: Is Gravity Direction Involved in the Inversion Effect?; (2) Motor Timing under Microgravity; (3) Perceived Self-Motion Assessed by Computer-Generated Animations: Complexity and Reliability; (4) Prolonged Weightlessness Reference Frames and Visual Symmetry Detection; (5) Mental Representation of Gravity During a Locomotor Task; and (6) Haptic Perception in Weightlessness: A Sense of Force or a Sense of Effort?

Stability of Permanent Magnets,

DTIC Science & Technology

1984-03-06

temperature. The effect of impacts, vibrations and external magnetic fields in less detail is illuminated. The new, accelerated methods of the study of...accelerated methods, developed by the author of the study of the stability of magnets and systems, which do not require prolonged time intervais...the accelerated methods proposed to them of the study of the stability of magnets will contribute to the accumulation of experimental results and to

Functional cream cheese supplemented with Bifidobacterium animalis subsp. lactis DSM 10140 and Lactobacillus reuteri DSM 20016 and prebiotics.

PubMed

Speranza, Barbara; Campaniello, Daniela; Monacis, Noemi; Bevilacqua, Antonio; Sinigaglia, Milena; Corbo, Maria Rosaria

2018-06-01

The aim of this study was to develop a functional fresh cream cheese with Bifidobacterium animalis subsp. lactis DSM 10140 or Lactobacillus reuteri DSM 20016 and prebiotics (inulin, FOS and lactulose). The research was divided into two steps: in vitro evaluation of the effects of prebiotic compounds; validation at laboratory level with production of functional cream mini-cheeses. Prebiotics showed a protective effect: B. animalis subsp. lactis DSM 10140 cultivability on Petri dishes was positively influenced by lactulose, whereas fructooligosaccharides (FOS) were the prebiotic compounds able to prolong Lb. reuteri DSM 20016 cultivability. At 30 °C, a prolongation of the death time (more than 300 days) was observed, while the controls showed death time values about 100 days. At 45 °C, death time values increased from 32.2 (control) to 33, 35, and 38 days in the samples added with FOS, inulin and lactulose, respectively. Lactulose and FOS were chosen to be added to cream mini-cheeses inoculated with B. animalis subsp. lactis DSM 10140 and Lb. reuteri DSM 20016, respectively; the proposed functional cream cheese resulted in a product with favourable conditions for the viability of both probiotics which maintained cultivable cells above the recommended level during 28 days of storage at 4 °C with good sensory characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Temporal patterns of sitting at work are associated with neck-shoulder pain in blue-collar workers: a cross-sectional analysis of accelerometer data in the DPHACTO study.

PubMed

Hallman, David M; Mathiassen, Svend Erik; Heiden, Marina; Gupta, Nidhi; Jørgensen, Marie Birk; Holtermann, Andreas

2016-07-01

Our aim was to examine the extent to which temporal patterns of sitting during occupational work and during leisure-time, assessed using accelerometry, are associated with intense neck-shoulder pain (NSP) in blue-collar workers. The population consisted of 659 Danish blue-collar workers. Accelerometers were attached to the thigh, hip, trunk and upper dominant arm to measure sitting time and physical activity across four consecutive days. Temporal sitting patterns were expressed separately for work and leisure by the proportion of total time spent sitting in brief bursts (0-5 min), moderate (>5-20 min) and prolonged (>20 min) periods. The peak NSP intensity during the previous 3 months was assessed using a numerical rating scale (range 0-10) and dichotomized into a lower (≤4) and higher (>4) NSP score. Logistic regression analyses with multiple adjustments for individual and occupational factors were performed to determine the association between brief, moderate and prolonged sitting periods, and NSP intensity. Time in brief bursts of occupational sitting was negatively associated with NSP intensity (adjusted OR 0.68, 95 % CI 0.48-0.98), while time in moderate periods of occupational sitting showed a positive association with NSP (adjusted OR 1.32, 95 % CI 1.04-1.69). Time in prolonged periods of occupational sitting was not associated with NSP (adjusted OR 0.78, 95 % CI 0.78-1.09). We found no significant association between brief, moderate or prolonged sitting periods during leisure, and NSP. Our findings indicate that the association between occupational sitting time and intense NSP among blue-collar workers is sensitive to the temporal pattern of sitting.

A dimeric form of a small-sized protein binder exhibits enhanced anti-tumor activity through prolonged blood circulation.

PubMed

Kim, Tae Yoon; Seo, Hyo-Deok; Lee, Joong-Jae; Kang, Jung Ae; Kim, Woo Sik; Kim, Hye-Min; Song, Ha-Yeon; Park, Ji Min; Lee, Dong-Eun; Kim, Hak-Sung

2018-06-10

Small-sized non-antibody scaffolds have attracted considerable interest as alternatives to immunoglobulin antibodies. However, their short half-life is considered a drawback in the development of therapeutic agents. Here we demonstrate that a homo-dimeric form of a repebody enhances the anti-tumor activity than a monomeric form through prolonged blood circulation. Spytag and spycatcher were genetically fused to the C-terminus of a respective human IL-6-specific repebody, and the resulting two repebody constructs were mixed at an equimolar ratio to produce a homo-dimeric form through interaction between spytag and spycatcher. The homo-dimeric repebody was detected as a single band in the SDS-PAGE analysis with an expected molecular size (78 kDa), showing high stability and homogeneity. The dimeric repebody was shown to simultaneously accommodate two hIL-6 molecules, and its binding affinity for hIL-6 was estimated to be comparable to a monomeric repebody. The serum concentration of the dimeric repebody was observed to be about 5.5 times higher than a monomeric repebody, consequently leading to considerably higher tumor suppression effect in human tumor xenograft mice. The present approach can be effectively used for prolonging the blood half-life of small-sized protein binders, resulting in enhanced therapeutic efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

Selective tissue factor/factor VIIa Inhibitor, ER-410660, and its prodrug, E5539, have anti-venous and anti-arterial thrombotic effects with a low risk of bleeding.

PubMed

Nagakura, Tadashi; Tabata, Kimiyo; Kira, Kazunobu; Hirota, Shinsuke; Clark, Richard; Matsuura, Fumiyoshi; Hiyoshi, Hironobu

2013-08-01

Many anticoagulant drugs target factors common to both the intrinsic and extrinsic coagulation pathways, which may lead to bleeding complications. Since the tissue factor (TF)/factor VIIa complex is associated with thrombosis onset and specifically activates the extrinsic coagulation pathway, compounds that inhibit this complex may provide therapeutic and/or prophylactic benefits with a decreased risk of bleeding. The in vitro enzyme profile and anticoagulation selectivity of the TF/VIIa complex inhibitor, ER-410660, and its prodrug E5539 were assessed using enzyme inhibitory and plasma clotting assays. In vivo effects of ER-410660 and E5539 were determined using a TF-induced, thrombin generation rhesus monkey model; a stasis-induced, venous thrombosis rat model; a photochemically induced, arterial thrombosis rat model; and a rat tail-cut bleeding model. ER-410660 selectively prolonged prothrombin time, but had a less potent anticoagulant effect on the intrinsic pathway. It also exhibited a dose-dependent inhibitory effect on thrombin generation caused by TF-injection in the rhesus monkey model. ER-410660 also reduced venous thrombus weights in the TF-administered, stasis-induced, venous thrombosis rat model and prolonged the occlusion time induced by arterial thrombus formation after vascular injury. The compound was capable of doubling the total bleeding time in the rat tail-cut model, albeit with a considerably higher dose compared to the effective dose in the venous and arterial thrombosis models. Moreover, E5539, an orally available ER-410660 prodrug, reduced the thrombin-anti-thrombin complex levels, induced by TF-injection, in a dose-dependent manner. Selective TF/VIIa inhibitors have potential as novel anticoagulants with a lower propensity for enhancing bleeding. Copyright © 2013 Elsevier Ltd. All rights reserved.

Normality of upper and lower peripheral pulse transit time of normotensive and hypertensive children.

PubMed

Foo, Jong Yong Abdiel

2007-08-01

The ankle-brachial index (ABI) is known to be indicative of sub-clinical peripheral arterial diseases that are correlated with cardiovascular disease risk factors like atherosclerosis or ischemic extremity. Due to its occluding measurement nature, this may not be appealing to less cooperative patients when multiple prolonged screening is required. A simple and non-intrusive approach termed pulse transit time ratio (PTTR) has recently shown to be potential surrogate marker for the prolonged ABI measurement. Other studies have also suggested that subjects with hypertension have stiffer arterial wall and thereby can confound transit time related parameters. Thus, it becomes important to understand the PTTR normality and difference of hypertensive children when compared to those measured from normotensive children. About 55 normotensive (39 male; aged 8.4 +/- 2.3 yr) and 4 hypertensive (4 male; aged 5-10 yr) Caucasian children were recruited from the same geographical location. A customized device was used to compute pulse transit time related measurements. Since the PTTR approach produced a delta value that was similar to that of ABI, possible inter-subject physiologic differences had limited confounding effects on the derived PTTR parameter. The obtained transit time measurements from the hypertensive children had lower pulse transit time value when compared to their normotensive counterparts. However, the statistical analysis indicated that they had insignificant PTTR difference (p > 0.01) from those seen in the normotensive children. The findings herein suggest that stiffer arterial wall may have confounding effects on the derived transit time related measurements but it is limited on the PTTR parameter. Similar to the ABI approach, PTTR may be only confounded by abnormal local changes in either of the measured peripheral arterial wall. Hence, the PTTR technique shows promise to be an ABI marker from this perspective.

Factors on working conditions and prolonged fatigue among physicians in Japan.

PubMed

Wada, Koji; Arimatsu, Mayuri; Yoshikawa, Toru; Oda, Susumu; Taniguchi, Hatsumi; Higashi, Toshiaki; Aizawa, Yoshiharu

2008-10-01

Fatigue among physicians could affect patients' safety and physicians' health. Fatigue could be caused by unfavorable working conditions. However, there have been no studies on the working conditions and fatigue among physicians in Japan. The objective of this study was to determine the factors on working conditions associated with prolonged fatigue among physicians in Japan. A questionnaire was mailed to physicians who graduated from one of the medical schools in Japan and who have had more than 3 years of experience in clinical practice. They were asked to assess 10 different aspects of their working conditions using a 5-point Likert scale. Prolonged fatigue was measured using the checklist of individual strength questionnaire. Multiple regression analysis was used to examine the multivariate relationship between the variables and prolonged fatigue. Data from 377 men and 101 women were analyzed in this study. For both male and female physicians, a harder workload was positively associated and better career satisfaction was negatively associated with prolonged fatigue. Prolonged fatigue was negatively associated with better relationships with other physicians and staff for male physicians and less personal time for female physicians. The adjusted variance in prolonged fatigue related to exposure variables was 26 and 29% in men and in women, respectively. The result of this study suggested that it is desirable to take these factors into consideration in the management of prolonged fatigue among physicians in Japan.

Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.

PubMed

Casey, Michael J; Wen, Xuerong; Kayler, Liise K; Aiyer, Ravi; Scornik, Juan C; Meier-Kriesche, Herwig-Ulf

2014-08-15

When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal. We retrospectively examined subjects transplanted at a single center between July 1, 1999 and December 1, 2009 with a non-death-related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only. We found 102 subjects with non-death-related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups, respectively (P=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% CI [1.37-24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group. These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.

Carry-over fluency induced by extreme prolongations: A new behavioral paradigm.

PubMed

Briley, P M; Barnes, M P; Kalinowski, J S

2016-04-01

Extreme prolongations, which can be generated via extreme delayed auditory feedback (DAF) (e.g., 250-500 ms) or mediated cognitively with timing applications (e.g., analog stopwatch) at 2 s per syllable, have long been behavioral techniques used to inhibit stuttering. Some therapies have used this rate solely to establish initial fluency, while others use extremely slowed speech to establish fluency and add other strategic techniques such as easy onsets and diaphragmatic breathing. Extreme prolongations generate effective, efficient, and immediate forward flowing fluent speech, removing the signature behaviors of discrete stuttering (i.e., syllable repetitions and audible and inaudible postural fixations). Prolonged use of extreme prolongations establishes carry-over fluency, which is spontaneous, effortless speech absent of most, if not all, overt and covert manifestations of stuttering. The creation of this immediate fluency and the immense potential of extreme prolongations to generate long periods of carry-over fluency have been overlooked by researchers and clinicians alike. Clinicians depart from these longer prolongation durations as they attempt to achieve the same fluent results at a near normal rate of speech. Clinicians assume they are re-teaching fluency and slow rates will give rise to more normal rates with less control, but without carry-over fluency, controls and cognitive mediation are always needed for the inherently unstable speech systems of persons who stutter to experience fluent speech. The assumption being that the speech system is untenable without some level of cognitive and motoric monitoring that is always necessary. The goal is omnipresent "near normal rate sounding fluency" with continuous mediation via cognitive and motoric processes. This pursuit of "normal sounding fluency" continues despite ever-present relapse. Relapse has become so common that acceptance of stuttering is the new therapy modality because relapse has come to be understood as somewhat inevitable. Researchers and clinicians fail to recognize that immediate amelioration of stuttering and its attendant carry-over fluency are signs of a different pathway to fluency. In this path, clinicians focus on extreme prolongations and the extent of their carry-over. While fluency is automatically generated under these extreme prolongations, the realization is that communication at this rate in routine speaking tasks is not feasible. The perceived solution is a systematic reduction in the duration of these prolongations, which attempts to approximate "normal speech." Typically, the reintroduction of speech at a normalized rate precipitates a laborious style that is undesirable to the person who stutters (PWS) and is discontinued, once departed from the comforts of the clinical setting. The inevitable typically occurs; the well-intentioned therapist instructs the PWS to focus on the techniques while speaking at a rate that is nearest normal speech, but the overlooked extreme prolongations are unlikely to ever be revisited. The foundation of this hypothesis is that the departure from fluency generators (e.g. extreme prolongations) is the cause of regression to the stuttering set point. In turn, we postulate that the continued use of extreme prolongations, as a solitary practice method, will establish and nurture different neural pathways that will create a modality of fluent speech, able to be experienced without cognitive or motoric mediation. This would therefore result in fewer occurrences of stuttering due to a phenomenon called carry-over fluency. Thus, we hypothesize that the use of extreme prolongations fosters neural pathways for fluent speech, which will result in carry-over fluency that does not require mediation by the speaker. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prolonged Exposure versus Dynamic Therapy for Adolescent PTSD: A Pilot Randomized Controlled Trial

ERIC Educational Resources Information Center

Gilboa-Schechtman, Eva; Foa, Edna B.; Shafran, Naama; Aderka, Idan M.; Powers, Mark B.; Rachamim, Lilach; Rosenbach, Lea; Yadin, Elna; Apter, Alan

2010-01-01

Objective: To examine the efficacy and maintenance of developmentally adapted prolonged exposure therapy for adolescents (PE-A) compared with active control time-limited dynamic therapy (TLDP-A) for decreasing posttraumatic and depressive symptoms in adolescent victims of single-event traumas. Method: Thirty-eight adolescents (12 to 18 years old)…

Effect of emergency physician burnout on patient waiting times.

PubMed

De Stefano, Carla; Philippon, Anne-Laure; Krastinova, Evguenia; Hausfater, Pierre; Riou, Bruno; Adnet, Frederic; Freund, Yonathan

2018-04-01

Burnout is common in emergency physicians. This syndrome may negatively affect patient care and alter work productivity. We seek to assess whether burnout of emergency physicians impacts waiting times in the emergency department. Prospective study in an academic ED. All patients who visited the main ED for a 4-month period in 2016 were included. Target waiting times are assigned by triage nurse to patients on arrival depending on their severity. The primary endpoint was an exceeded target waiting time for ED patients. All emergency physicians were surveyed by a psychologist to assess their level of burnout using the Maslach Burnout Inventory. We defined the level of burnout of the day in the ED as the mean burnout level of the physicians working that day (8:30 to the 8:30 the next day). A logistic regression model was performed to assess whether burnout level of the day was independently associated with prolonged waiting times, along with previously reported predictors. Target waiting time was exceeded in 7524 patients (59%). Twenty-six emergency physicians were surveyed. Median burnout score was 35 [Interquartile (24-49)]. A burnout level of the day higher than 35 was independently associated with an exceeded target waiting time (adjusted odds ratio 1.54, 95% confidence interval 1.39-1.70), together with previously reported predictors (i.e., day of the week, time of the day, trauma, age and daily census). Burnout of emergency physicians was independently associated with a prolonged waiting time for patients visiting the ED.

The influence of a seated break on prolonged standing induced low back pain development.

PubMed

Gallagher, Kaitlin M; Campbell, Troy; Callaghan, Jack P

2014-01-01

With the recent attention to 'sitting disease', health practitioners and scientists are promoting standing in the workplace to decrease sedentary time, despite a high prevalence of low back pain (LBP) development during prolonged standing. The purpose of this study was to assess how a seated break inserted between bouts of prolonged standing would influence LBP development, posture and movement. A total of 20 participants stood for 45 minutes, sat for 15 minutes and repeated this sequence while lumbar and thoracic angles were measured, and LBP visual analogue scale reports were taken. Of the sample, 55% participants reported LBP in standing. A stand to sit ratio of 3:1 did not provide lasting recovery of LBP from standing and pain developers utilised a limited range of their lumbar spine angle and increased thoracic extension, resulting in static postures that caused tissue aggravation that was not resolved after 15 minutes of sitting. Prolonged standing in the workplace has the potential to result in LBP for some workers and alternate ways to reduce sedentary time should be investigated.

Intrarectal pressures and balloon expulsion related to evacuation proctography.

PubMed Central

Halligan, S; Thomas, J; Bartram, C

1995-01-01

Seventy four patients with constipation were examined by standard evacuation proctography and then attempted to expel a small, non-deformable rectal balloon, connected to a pressure transducer to measure intrarectal pressure. Simultaneous imaging related the intrarectal position of the balloon to rectal deformity. Inability to expel the balloon was associated proctographically with prolonged evacuation, incomplete evacuation, reduced anal canal diameter, and acute anorectal angulation during evacuation. The presence and size of rectocoele or intussusception was unrelated to voiding of paste or balloon. An independent linear combination of pelvic floor descent and evacuation time on proctography correctly predicted maximum intrarectal pressure in 74% of cases. No patient with both prolonged evacuation and reduced pelvic floor descent on proctography could void the balloon, as maximum intrarectal pressure was reduced in this group. A prolonged evacuation time on proctography, in combination with reduced pelvic floor descent, suggests defecatory disorder may be caused by inability to raise intrarectal pressure. A diagnosis of anismus should not be made on proctography solely on the basis of incomplete/prolonged evacuation, as this may simply reflect inadequate straining. PMID:7672656

Bisphenol A Exposure and Cardiac Electrical Conduction in Excised Rat Hearts

PubMed Central

Jaimes, Rafael; Asfour, Huda; Swift, Luther M.; Wengrowski, Anastasia M.; Sarvazyan, Narine; Kay, Matthew W.

2014-01-01

Background: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. Objectives: The goal of our study was to measure the effect of BPA (0.1–100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. Methods: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Results: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1–100 μM BPA), prolonged action potential duration (1–100 μM BPA), and delayed atrioventricular conduction (10–100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Conclusions: Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA’s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations. Citation: Posnack NG, Jaimes R III, Asfour H, Swift LM, Wengrowski AM, Sarvazyan N, Kay MW. 2014. Bisphenol A exposure and cardiac electrical conduction in excised rat hearts. Environ Health Perspect 122:384–390; http://dx.doi.org/10.1289/ehp.1206157 PMID:24487307

The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer.

PubMed

Chen, M; Jiang, G L; Fu, X L; Wang, L J; Qian, H; Chen, G Y; Zhao, S; Liu, T F

2000-04-01

A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). From Jan. 1990 to Dec. 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. OTT had been shortened in 64 patients because of an accelerated hyperfractioned irradiation, while OTT was prolonged i n 114 patients due to interruptions of irradiation courses. The main ca uses of interruption were machine breakdown or delayed preparations of c errobend block for boost fields (55%), holidays (11%) and treatment toxi city and side effects (34%). Patients tre ated with prolonged OTT (> 45 days) had significant poorer local progression-free survival than whom with OTT of

Psychotherapy for Military-Related PTSD: A Review of Randomized Clinical Trials.

PubMed

Steenkamp, Maria M; Litz, Brett T; Hoge, Charles W; Marmar, Charles R

2015-08-04

Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder common among military personnel and veterans. First-line psychotherapies most often recommended for PTSD consist mainly of "trauma-focused" psychotherapies that involve focusing on details of the trauma or associated cognitive and emotional effects. To examine the effectiveness of psychotherapies for PTSD in military and veteran populations. PubMed, PsycINFO, and PILOTS were searched for randomized clinical trials (RCTs) of individual and group psychotherapies for PTSD in military personnel and veterans, published from January 1980 to March 1, 2015. We also searched reference lists of articles, selected reviews, and meta-analyses. Of 891 publications initially identified, 36 were included. Two trauma-focused therapies, cognitive processing therapy (CPT) and prolonged exposure, have been the most frequently studied psychotherapies for military-related PTSD. Five RCTs of CPT (that included 481 patients) and 4 RCTs of prolonged exposure (that included 402 patients) met inclusion criteria. Focusing on intent-to-treat outcomes, within-group posttreatment effect sizes for CPT and prolonged exposure were large (Cohen d range, 0.78-1.10). CPT and prolonged exposure also outperformed waitlist and treatment-as-usual control conditions. Forty-nine percent to 70% of participants receiving CPT and prolonged exposure attained clinically meaningful symptom improvement (defined as a 10- to 12-point decrease in interviewer-assessed or self-reported symptoms). However, mean posttreatment scores for CPT and prolonged exposure remained at or above clinical criteria for PTSD, and approximately two-thirds of patients receiving CPT or prolonged exposure retained their PTSD diagnosis after treatment (range, 60%-72%). CPT and prolonged exposure were marginally superior compared with non-trauma-focused psychotherapy comparison conditions. In military and veteran populations, trials of the first-line trauma-focused interventions CPT and prolonged exposure have shown clinically meaningful improvements for many patients with PTSD. However, nonresponse rates have been high, many patients continue to have symptoms, and trauma-focused interventions show marginally superior results compared with active control conditions. There is a need for improvement in existing PTSD treatments and for development and testing of novel evidence-based treatments, both trauma-focused and non-trauma-focused.

Cocaine-like discriminative stimulus effects of alpha-pyrrolidinovalerophenone, methcathinone and their 3,4-methylenedioxy or 4-methyl analogs in rhesus monkeys.

PubMed

Smith, Douglas A; Negus, S Stevens; Poklis, Justin L; Blough, Bruce E; Banks, Matthew L

2017-09-01

Synthetic cathinones are beta-ketone amphetamine analogs that have emerged as a heterogeneous class of abused compounds that function as either monoamine transporter substrates or inhibitors. Pre-clinical drug discrimination procedures are useful for interrogating structure-activity relationships of abuse-related drug effects; however, in vivo structure-activity relationship comparisons between synthetic cathinones with different mechanisms of action are lacking. The aim of the present study was to determine whether the cocaine-like discriminative stimulus effects of the monoamine transporter inhibitor alpha-pyrrolidinovalerophenone (alpha-PVP) and the monoamine transporter substrate methcathinone were differentially sensitive to 3,4-methylenedioxy and 4-methyl substitutions. Male rhesus monkeys (n = 4) were trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure. Potency and timecourse of cocaine-like discriminative stimulus effects were determined for (±)-alpha-PVP, (±)-methcathinone and their 3,4-methylenedioxy or 4-methyl analogs. Alpha-PVP and methcathinone produced dose- and time-dependent cocaine-like effects. A 3,4-methylenedioxy addition to either alpha-PVP or methcathinone (methylone) did not alter the potency or efficacy to produce cocaine-like effects, but did prolong the time course. A 4-methyl addition to alpha-PVP (pyrovalerone) did not alter the potency or efficacy to produce cocaine-like effects, but did prolong the time course. In contrast, addition of a 4-methyl moiety to methcathinone (4MMC; mephedrone) significantly attenuated efficacy to produce cocaine-like effects. Overall, these results suggest different structural requirements for cocaine-like discriminative stimulus effects of monoamine transporter inhibitor and substrate synthetic cathinone analogs. Given that 4MMC is more hydrophobic than MDMC, these results suggest that hydrophobicity may be an important determinant for limiting monoamine transporter substrate abuse-related behavioral effects. © 2016 Society for the Study of Addiction.

Kerato-lenticular ocular deposits and visual impairment with prolonged chlorpromazine use: A case series.

PubMed

Gowda, Guru S; Hegde, Aditya; Shanbhag, Vandita; Narayanaswamy, Janardhanan C; Jaisoorya, T S

2017-02-01

Chlorpromazine is a low potency "typical" antipsychotic agent used to treat schizophrenia. It continues to be prescribed frequently in India owing to its lower cost. There have been previous reports of ocular adverse effects with prolonged use of chlorpromazine. We report three patients who developed corneal and lenticular opacities secondary to prolonged chlorpromazine use leading to visual impairment. Early detection of ocular deposits and switching over to risperidone from chlorpromazine helped in the reversal of chlorpromazine- induced ocular side effects in one of them. The case series further adds evidence to the causative relationship between chlorpromazine and ocular side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Pyrilamine-induced prolonged QT interval in adolescent with drug overdose.

PubMed

Paudel, Govinda; Syed, Muhammad; Kalantre, Sarika; Sharma, Jayendra

2011-10-01

The widespread availability of antihistamines in many over-the-counter preparations can lead to significant hazard to the public because of their possible link to potential ventricular arrhythmias secondary to prolongation of QT interval. The effect can be further compounded by the use of other commonly used medications such as macrolides, antifungal agents, antipsychotics, and other antihistamine-containing preparations. The effect of antihistamines on QT interval is not a class effect but is unique to certain medications. Pyrilamine, a first-generation antihistaminic agent, is considered safe as there are no reports regarding its cardiac toxicity available in literature. We report a case of an adolescent with prolonged QT interval after an overdose of pyrilamine.

A Cluster Randomized Controlled Trial to Reduce Office Workers' Sitting Time: Effect on Activity Outcomes.

PubMed

Healy, Genevieve N; Eakin, Elizabeth G; Owen, Neville; Lamontagne, Anthony D; Moodie, Marj; Winkler, Elisabeth A H; Fjeldsoe, Brianna S; Wiesner, Glen; Willenberg, Lisa; Dunstan, David W

2016-09-01

This study aimed to evaluate the initial and long-term effectiveness of a workplace intervention compared with usual practice, targeting the reduction of sitting on activity outcomes. Office worksites (≥1 km apart) from a single organization in Victoria, Australia, were cluster randomized to intervention (n = 7) or control (n = 7). Participants were 231 desk-based office workers (5-39 participants per worksite) working at least 0.6 full-time equivalent. The workplace-delivered intervention addressed organizational, physical environment, and individual behavioral changes to reduce sitting time. Assessments occurred at baseline, 3 months, and 12 months, with the primary outcome participants' objectively measured (activPAL3 device) workplace sitting time (minutes per 8-h workday). Secondary activity outcomes were workplace time spent standing, stepping (light, moderate to vigorous, and total), and in prolonged (≥30 min) sitting bouts (hours per 8-h workday); usual duration of workplace sitting bouts; and overall sitting, standing, and stepping time (minutes per 16-h day). Analysis was by linear mixed models, accounting for repeated-measures and clustering and adjusting for baseline values and potential confounders. At baseline, on average, participants (68% women; mean ± SD age = 45.6 ± 9.4 yr) sat, stood, and stepped for 78.8% ± 9.5%, 14.3% ± 8.2%, and 6.9% ± 2.9% of work hours, respectively. Workplace sitting time was significantly reduced in the intervention group compared with the controls at 3 months (-99.1 [95% confidence interval = -116.3 to -81.8] min per 8-h workday) and 12 months (-45.4 [-64.6 to -26.2] min per 8-h workday). Significant intervention effects (all favoring intervention) were observed for standing, prolonged sitting, and usual sitting bout duration at work, as well as overall sitting and standing time, with no significant or meaningful effects observed for stepping. This workplace-delivered multicomponent intervention was successful at reducing workplace and overall daily sitting time in both the short term and the long term.

Saline Flush After Rocuronium Bolus Reduces Onset Time and Prolongs Duration of Effect: A Randomized Clinical Trial.

PubMed

Ishigaki, Sayaka; Masui, Kenichi; Kazama, Tomiei

2016-03-01

Circulatory factors modify the onset time of neuromuscular-blocking drugs. Therefore, we hypothesized that infusion of a saline flush immediately after rocuronium administration would shorten the onset time without influencing the duration of the rocuronium effect. Forty-eight patients were randomly allocated to the control or saline flush group. Anesthesia was induced and maintained with propofol and remifentanil, and all patients received 0.6 mg/kg rocuronium in 10 mL of normal saline. In the saline flush group, 20 mL normal saline was immediately infused after rocuronium administration. Neuromuscular blockade was assessed using acceleromyography at the adductor pollicis muscle with train-of-four (TOF) stimulation. The neuromuscular indices for rocuronium were calculated as follows: the latent onset time, defined as the time from the start of rocuronium infusion until first occurrence of depression of the first twitch of the TOF (T1) ≥5%; onset time, defined as the time from the start of rocuronium infusion until first occurrence of depression of the T1 ≥95%; clinical duration, defined as the time from the start of rocuronium administration until T1 recovered to 25% of the final T1 value; recovery index, defined as the time for recovery of T1 from 25% to 75% of the final T1 value; and the total recovery time, defined as the time from the start of rocuronium administration until reaching a TOF ratio of 0.9. Significance was designated at P <0.05. The measured latent onset time and onset time were significantly shorter in the saline flush group than the control group by 15 seconds (95.2% confidence interval, 0-15, P = 0.007) and 15 seconds (0-30, P = 0.018), respectively. Saline flush significantly depressed the T1 height at 30, 45, and 60 seconds after the rocuronium bolus by 17%, 24%, and 14%, respectively. In addition, the recovery phase was significantly prolonged in the saline flush group. The mean clinical duration (5th-95th percentile range) in the saline flush group and control group was 35 minutes (27-63 minutes) and 31 minutes (19-48 minutes; P = 0.032), respectively; the recovery index was 13 minutes (8-25 minutes) and 10 minutes (7-19 minutes; P = 0.019), respectively; and the total recovery time was 61 minutes (44-108 minutes) and 50 minutes (35-93 minutes; P = 0.048), respectively. Administering a 20-mL saline flush immediately after infusion of 0.6 mg/kg rocuronium in 10 mL normal saline shortened the onset time and prolonged the recovery phase of neuromuscular blockade.

Distributed Multihop Clustering Approach for Wireless Sensor Networks

NASA Astrophysics Data System (ADS)

Israr, Nauman; Awan, Irfan

Prolonging the life time of Wireless Sensor Networks (WSNs) has been the focus of current research. One of the issues that needs to be addressed along with prolonging the network life time is to ensure uniform energy consumption across the network in WSNs especially in case of random network deployment. Cluster based routing algorithms are believed to be the best choice for WSNs because they work on the principle of divide and conquer and also improve the network life time considerably compared to flat based routing schemes. In this paper we propose a new routing strategy based on two layers clustering which exploits the redundancy property of the network in order to minimise duplicate data transmission and also make the intercluster and intracluster communication multihop. The proposed algorithm makes use of the nodes in a network whose area coverage is covered by the neighbouring nodes. These nodes are marked as temporary cluster heads and later use these temporary cluster heads randomly for multihop intercluster communication. Performance studies indicate that the proposed algorithm solves effectively the problem of load balancing across the network and is more energy efficient compared to the enhanced version of widely used Leach algorithm.

PEGylation prolongs the pulmonary retention of an anti-IL-17A Fab' antibody fragment after pulmonary delivery in three different species.

PubMed

Freches, Danielle; Patil, Harshad P; Machado Franco, Maria; Uyttenhove, Catherine; Heywood, Sam; Vanbever, Rita

2017-04-15

The PEGylation of antibody fragments has been shown to greatly prolong their residence time in the lungs in mice. The purpose of this research was to confirm the effect of PEGylation in higher animal species, that is, the rat and the rabbit. An anti-IL-17A Fab' antibody fragment was conjugated to a two-armed 40kDa polyethylene glycol (PEG) via site-selective thiol PEGylation. PEGylation did not significantly alter the binding activity of the Fab' fragment but it largely enhanced its inhibitory potency. PEGylation increased the residence time of the Fab' in the lungs of mice, rats and rabbits. Following intratracheal administration, the unconjugated Fab' was cleared from the lungs within 24h while large quantities of the PEGylated Fab' remained present up to 48h. No significant differences in clearance were noted between the three animal species although there was a tendency of longer residence time in higher species. PEGylation represents a promising approach to sustain the presence of antibody fragments in the lungs and to enhance their therapeutic efficacy in respiratory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Prolonged phone-call posture causes changes of ulnar motor nerve conduction across elbow.

PubMed

Padua, Luca; Coraci, Daniele; Erra, Carmen; Doneddu, Pietro Emiliano; Granata, Giuseppe; Rossini, Paolo Maria

2016-08-01

Postures and work-hobby activities may play a role in the origin and progression of ulnar neuropathy at the elbow (UNE), whose occurrence appears to be increasing. The time spent on mobile-phone has increased in the last decades leading to an increased time spent with flexed elbow (prolonged-phone-posture, PPP). We aimed to assess the effect of PPP both in patients with symptoms of UNE and in symptom-free subjects. Patients with pure sensory symptoms of UNE and negative neurophysiological tests (MIN-UNE) and symptom-free subjects were enrolled. We evaluated ulnar motor nerve conduction velocity across elbow at baseline and after 6, 9, 12, 15, and 18min of PPP in both groups. Fifty-six symptom-free subjects and fifty-eight patients were enrolled. Globally 186 ulnar nerves from 114 subjects were studied. Conduction velocity of ulnar nerve across the elbow significantly changed over PPP time in patients with MIN-UNE, showing a different evolution between the two groups. PPP causes a modification of ulnar nerve functionality in patients with MIN-UNE. PPP may cause transient stress of ulnar nerve at elbow. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Reduction of capacity decay in vanadium flow batteries by an electrolyte-reflow method

NASA Astrophysics Data System (ADS)

Wang, Ke; Liu, Le; Xi, Jingyu; Wu, Zenghua; Qiu, Xinping

2017-01-01

Electrolyte imbalance is a major issue with Vanadium flow batteries (VFBs) as it has a significant impact on electrolyte utilization and cycle life over extended charge-discharge cycling. This work seeks to reduce capacity decay and prolong cycle life of VFBs by adopting a novel electrolyte-reflow method. Different current density and various start-up time of the method are investigated in the charge-discharge tests. The results show that the capacity decay rate is reduced markedly and the cycle life is prolonged substantially by this method. In addition, the coulomb efficiency, voltage efficiency and energy efficiency remain stable during the whole cycle life test, which indicates this method has little impact on the long lifetime performance of the VFBs. The method is low-cost, simple, effective, and can be applied in industrial VFB productions.

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Raman spectra of Nd/Sn cosubstituted Ba6-3xSm8+2xTi18O54 microwave dielectric ceramics

NASA Astrophysics Data System (ADS)

Wu, S. Y.; Li, Y.; Chen, X. M.

2004-11-01

The Raman spectra and dielectric properties of Nd /Sn cosubstituted Ba6-3xSm8+2xTi18O54 (x =2/3) microwave dielectric ceramics were discussed as the functions of composition and sintering time. The peaks in 753cm-1 were caused by the second order scatter. The peaks in 425 and 403cm-1 became sharper with prolonging sintering time, and this reflected the increased lattice defects. The shoulder peak near 292cm-1 was caused by the octahedral tilt when A site is Nd3+. The Raman shifts in 590, 520, 280, and 232cm-1 indicated no obvious change in position, but all peaks became sharper with prolonging sintering time. This indicated the increased ordering degree of A-site cations. With prolonging sintering time, the Qf factor (Q is the inverse of dielectric loss, tan δ, and f is the resonant frequency) increased, and the temperature coefficient of resonant frequency significantly decreased or became more negative, while the dielectric constant indicated no significant variation.

The effectiveness of Grief-Help, a cognitive behavioural treatment for prolonged grief in children: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background There is growing recognition of a syndrome of disturbed grief referred to as prolonged grief disorder (PGD). PGD is mostly studied in adults, but clinically significant PGD symptoms have also been observed in children and adolescents. Yet, to date no effective treatment for childhood PGD exists. The aims of this study are: (1) to investigate the effectiveness of Grief-Help, a nine-session cognitive-behavioural treatment for childhood PGD, combined with five sessions of parental counselling, immediately after the treatment and at three, six and twelve months follow-up; (2) to examine tentative mediators of the effects of Grief-Help, (i.e., maladaptive cognitions and behaviours and positive parenting), and (3) to determine whether demographic variables, child personality, as well as symptoms of PGD, anxiety, and depression in parents moderate the treatment effectiveness. Methods/Design We will conduct a Randomised Controlled Trial (RCT) in which 160 children and adolescents aged 8–18 years are randomly allocated to cognitive behavioural Grief-Help or to a supportive counselling intervention; both treatments are combined with five sessions of parental counselling. We will recruit participants from clinics for mental health in the Netherlands. The primary outcome measure will be the severity of Prolonged Grief Disorder symptoms according to the Inventory of Prolonged Grief for Children (IPG-C). Secondary outcomes will include PTSD, depression and parent-rated internalizing and externalizing problems. Mediators like positive parenting and maladaptive cognitions and behaviours will be identified. We will also examine possible moderators including demographic variables (e.g. time since loss, cause of death), psychopathology symptoms in parents (PGD, anxiety and depression) and child personality. Assessments will take place in both groups at baseline, after the treatment-phase and three, six and twelve months after the post-treatment assessment. Discussion We aim to contribute to the improvement of mental health care for children and adolescents suffering from loss. By comparing Grief-Help with supportive counselling, and by investigating mediators and moderators of its effectiveness we hope to provide new insights in the effects of interventions for bereaved children, and their mechanisms of change. Trial registration Netherlands Trial Register NTR3854 PMID:24252587

Effect of the Duration Time of a Nuclear Accident on Radiological Health Consequences

PubMed Central

Jeong, Hyojoon; Park, Misun; Jeong, Haesun; Hwang, Wontae; Kim, Eunhan; Han, Moonhee

2014-01-01

This study aimed to quantify the effect of duration time of a nuclear accident on the radiation dose of a densely populated area and the resulting acute health effects. In the case of nuclear accidents, the total emissions of radioactive materials can be classified into several categories. Therefore, the release information is very important for the assessment of risk to the public. We confirmed that when the duration time of the emissions are prolonged to 7 hours, the concentrations of radioactive substances in the ambient air are reduced by 50% compared to that when the duration time of emission is one hour. This means that the risk evaluation using only the first wind direction of an accident is very conservative, so it has to be used as a screening level for the risk assessment. Furthermore, it is judged that the proper control of the emission time of a nuclear accident can minimize the health effects on residents. PMID:24619120

In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

PubMed

Liu, Y H; Hawk, R M; Ramaprasad, S

1995-01-01

RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

The influence of dog ownership on objective measures of free-living physical activity and sedentary behaviour in community-dwelling older adults: a longitudinal case-controlled study.

PubMed

Dall, Philippa Margaret; Ellis, Sarah Lesley Helen; Ellis, Brian Martin; Grant, P Margaret; Colyer, Alison; Gee, Nancy Renee; Granat, Malcolm Howard; Mills, Daniel Simon

2017-06-09

There is some evidence to suggest that dog ownership may improve physical activity (PA) among older adults, but to date, studies examining this, have either depended on self-report or incomplete datasets due to the type of activity monitor used to record physical activity. Additionally, the effect of dog ownership on sedentary behaviour (SB) has not been explored. The aim of the current study was to address these issues by using activPAL monitors to evaluate the influence of dog ownership on health enhancing PA and SB in a longitudinal study of independently-mobile, community-dwelling older adults. Study participants (43 pairs of dog owners and non-dog owners, matched on a range of demographic variables) wore an activPAL monitor continuously for three, one-week data collection periods over the course of a year. Participants also reported information about their own and their dog demographics, caring responsibilities, and completed a diary of wake times. Diary data was used to isolate waking times, and outcome measures of time spent walking, time spent walking at a moderate cadence (>100 steps/min), time spent standing, time spent sitting, number of sitting events (continuous periods of sitting), and the number of and of time spent sitting in prolonged events (>30 min). For each measure, a linear mixed effects model with dog ownership as a fixed effect, and a random effects structure of measurement point nested in participant nested in pair was used to assess the effect of dog ownership. Owning a dog indicated a large, potentially health improving, average effect of 22 min additional time spent walking, 95%CI (12, 34), and 2760 additional steps per day, 95%CI (1667, 3991), with this additional walking undertaken at a moderate intensity cadence. Dog owners had significantly fewer sitting events. However, there were no significant differences between the groups for either the total time spent sitting, or the number or duration of prolonged sedentary events. The scale of the influence of dog ownership on PA found in this study, indicates that future research regarding PA in older adults should assess and report dog ownership and/or dog walking status.

Influence of environmental pH on G2-phase arrest caused by ionizing radiation.

PubMed

Park, Heon Joo; Lee, Sang Hwa; Chung, HyunSook; Rhee, Yun Hee; Lim, Byung Uk; Ha, Sung Whan; Griffin, Robert J; Lee, Hyung Sik; Song, Chang Won; Choi, Eun Kyung

2003-01-01

We investigated the effects of an acidic environment on the G2/M-phase arrest, apoptosis, clonogenic death, and changes in cyclin B1-CDC2 kinase activity caused by a 4-Gy irradiation in RKO.C human colorectal cancer cells in vitro. The time to reach peak G2/M-phase arrest after irradiation was delayed in pH 6.6 medium compared to that in pH 7.5 medium. Furthermore, the radiation-induced G2/M-phase arrest decayed more slowly in pH 6.6 medium than in pH 7.5 medium. Finally, there was less radiation-induced apoptosis and clonogenic cell death in pH 6.6 medium than in pH 7.5 medium. It appeared that the prolongation of G2-phase arrest after irradiation in the acidic environment allowed for greater repair of radiation-induced DNA damage, thereby decreasing the radiation-induced cell death. The prolongation of G2-phase arrest after irradiation in the acidic pH environment appeared to be related at least in part to a prolongation of the phosphorylation of CDC2, which inhibited cyclin B1-CDC2 kinase activity.

Attending to items in working memory: Evidence that refreshing and memory search are closely related

PubMed Central

Vergauwe, Evie; Cowan, Nelson

2014-01-01

Refreshing refers to the use of attention to reactivate items in working memory (WM). The current study aims at testing the hypothesis that refreshing is closely related to memory search. The assumption is that refreshing and memory search both rely on a basic covert memory process that quickly retrieves the memory items into the focus of attention, thereby reactivating the information (Cowan, 1992; Vergauwe & Cowan, 2014). Consistent with the idea that people use their attention to prevent loss from WM, previous research has shown that increasing the proportion of time during which attention is occupied by concurrent processing, thereby preventing refreshing, results in poorer recall performance in complex span tasks (Barrouillet, Portrat, & Camos, 2011). Here, we tested whether recall performance is differentially affected by prolonged attentional capture caused by memory search. If memory search and refreshing both rely on retrieval from WM, then prolonged attentional capture caused by memory search should not lead to forgetting because memory items are assumed to be reactivated during memory search, in the same way as they would if that period of time were to be used for refreshing. Consistent with this idea, prolonged attentional capture had a disruptive effect when it was caused by the need to retrieve knowledge from long-term memory but not when it was caused by the need to search through the content of WM. The current results support the idea that refreshing operates through a process of retrieval of information into the focus of attention. PMID:25361821

Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

PubMed

Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

2016-09-01

The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Organizational factors affecting length of stay in the emergency department: initial observational study.

PubMed

Bashkin, Osnat; Caspi, Sigalit; Haligoa, Rachel; Mizrahi, Sari; Stalnikowicz, Ruth

2015-01-01

Length of stay (LOS) is considered a key measure of emergency department throughput, and from the perspective of the patient, it is perceived as a measure of healthcare service quality. Prolonged LOS can be caused by various internal and external factors. This study examined LOS in the emergency department and explored the main factors that influence LOS and cause delay in patient care. Observations of 105 patients were performed over a 3-month period at the emergency room of a community urban hospital. Observers monitored patients from the moment of entrance to the department until discharge or admission to another hospital ward. Analysis revealed a general average total emergency department LOS of 438 min. Significant differences in average LOS were found between admitted patients (Mean = 544 min, SD = 323 min) and discharged patients (Mean = 291 min, SD = 286 min). In addition, nurse and physician change of shifts and admissions to hospital wards were found to be significant factors associated with LOS. Using an Ishikawa causal diagram, we explored various latent organizational factors that may prolong this time. The study identified several factors that are associated with high average emergency department LOS. High LOS may lead to increases in expenditures and may have implications for patient safety, whereas certain organizational changes, communication improvement, and time management may have a positive effect on it. Interdisciplinary methods can be used to explore factors causing prolonged emergency department LOS and contribute to a better understanding of them.

Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice.

PubMed

Anisimov, V N; Khavinson, V Kh; Alimova, I N; Semchenko, A V; Yashin, A I

2002-08-01

Female transgenic FVB/N mice carrying the breast cancer gene HER-2/neu received epithalon (Ala-Glu-Asp-Gly) in a dose of 1 mg subcutaneously 5 times a week to from the 2nd month of life to death. Epithalon prolonged the average and maximum lifetimes of mice by 13.5 (p<0.05) and 13.9%, respectively. The peptide prolonged the average lifetime of animals without neoplasms (by 34.2%, p<0.05). Epithalon decelerated the development of age-related disturbances in reproductive activity and suppressed the formation of neoplasms. The peptide decreased the incidence of breast adenocarcinomas, lungs metastases (by 1.6 times, p<0.05), and multiple tumors (by 2 times). Epithalon 3.7-fold increased the number of mice without breast tumors (p<0.05), while the number of animals with 6 or more breast tumors decreased by 3 times (p<0.05). Epithalon prolonged the lifetime of mice with breast tumors by 1.4 times (p<0.05). These results indicate that Epithalon possesses geroprotective activity and inhibits breast carcinogenesis in transgenic mice, which is probably related to suppression of HER-2/neu expression.

Association between screen time and snack consumption in children and adolescents: The CASPIAN-IV study.

PubMed

Kelishadi, Roya; Mozafarian, Nafiseh; Qorbani, Mostafa; Maracy, Mohammad Reza; Motlagh, Mohammad Esmaeil; Safiri, Saeid; Ardalan, Gelayol; Asayesh, Hamid; Rezaei, Fatemeh; Heshmat, Ramin

2017-02-01

The relationship between screen time (ST) and the frequency of snack consumption in a national sample of Iranian children and adolescents was assessed. The present nationwide survey was conducted on 14,880 school students living in urban and rural areas of 30 provinces in Iran. Trained healthcare providers conducted the physical examination and completed the questionnaire of the World Health Organization - Global School-Based Student Health Survey (WHO-GSHS). The association between ST (total time spent watching TV and using a computer in leisure time) and the frequency of snack consumption was determined using ordinal logistic regression analysis. The subjects were 13,486 students out of the 14,880 invited including 50.8% boys. The mean (SD) age of participants was 12.47 (3.36) years. In multivariate models, for students who had prolonged ST (more than 4 h/day), the odds of daily consumption of sweets (odds ratio, OR 1.25; 95% CI 1.14-1.4), salty snacks (OR 1.6; 95% CI 1.5-1.76), soft drinks (OR 1.52; 95% CI 1.4-1.7), canned fruit juice (OR 1.3; 95% CI 1.2-1.4), and fast food (OR 1.53; 95% CI 1.4-1.7) were higher compared to those with low ST. Furthermore, the odds of daily consumption of milk in students who had prolonged ST (more than 4 h/day) were lower compared to those with low ST (OR 0.9; 95% CI 0.8-0.99). Prolonged time spent watching TV and using a computer during leisure time might be associated with unhealthy dietary habits. Moreover, inactivity induced by prolonged ST may also lead to unhealthy dietary habits and in turn excess weight in children and adolescents.

Laparoscopic versus open incisional hernia repair: a retrospective cohort study with costs analysis on 269 patients.

PubMed

Soliani, G; De Troia, A; Portinari, M; Targa, S; Carcoforo, P; Vasquez, G; Fisichella, P M; Feo, C V

2017-08-01

To compare clinical outcomes and institutional costs of elective laparoscopic and open incisional hernia mesh repairs and to identify independent predictors of prolonged operative time and hospital length of stay (LOS). Retrospective observational cohort study on 269 consecutive patients who underwent elective incisional hernia mesh repair, laparoscopic group (N = 94) and open group (N = 175), between May 2004 and July 2014. Operative time was shorter in the laparoscopic versus open group (p < 0.0001). Perioperative morbidity and mortality were similar in the two groups. Patients in the laparoscopic group were discharged a median of 2 days earlier (p < 0.0001). At a median follow-up over 50 months, no difference in hernia recurrence was detected between the groups. In laparoscopic group total institutional costs were lower (p = 0.02). At Cox regression analysis adjusted for potential confounders, large wall defect (W3) and higher operative risk (ASA score 3-4) were associated with prolonged operative time, while midline hernia site was associated with increased hospital LOS. Open surgical approach was associated with prolongation of both operative time and LOS. Laparoscopic approach may be considered safely to all patients for incisional hernia repair, regardless of patients' characteristics (age, gender, BMI, ASA score, comorbidities) and size of the wall defect (W2-3), with the advantage of shorter operating time and hospital LOS that yields reduced total institutional costs. Patients with higher ASA score and large hernia defects are at risk of prolonged operative time, while an open approach is associated with longer duration of surgical operation and hospital LOS.

Intranasal infusion of melanocortin receptor four (MC4R) antagonist to rats ameliorates development of depression and anxiety related symptoms induced by single prolonged stress.

PubMed

Serova, Lidia I; Laukova, Marcela; Alaluf, Lishay G; Sabban, Esther L

2013-08-01

Brain melanocortinergic systems and specifically melanocortin receptor four (MC4R) are implicated in modulation of anxiety- and depressive-like behavior induced by mild or moderate stress. Here we examine whether blockage of central MC4Rs with HS014 before severe traumatic stress may protect against development of anxiety and depression co-morbid with post-traumatic stress disorder (PTSD). Male rats were treated intranasally (IN) with vehicle or varied doses of HS014, 30min prior to single prolonged stress (SPS) animal model of PTSD. IN administration of 100μg HS014 pre-SPS improved despair behavior in forced swim (FS) immediately after immobilization stress part of SPS protocol. During all 4 intervals of 20min FS these rats spent less time immobile than rats given vehicle or 3.5ng HS014. This dose of HS014 also had a long-term beneficial effect manifested as reduction of immobility time in forced swim test performed after SPS. However, both HS014 doses were effective in ameliorating development of anxiety-like behavior after traumatic stress. Thus, rats given IN HS014 prior to SPS exhibited less open arms (OA) visits in elevated plus maze (EPM), spent longer time in OA and less in closed arms, had lower anxiety index, higher risk assessment and more head dips over borders in OA. They also spent longer time in the center of the open field and defecated less. Reduced grooming behavior in EPM was observed with 100μg HS014. This is the first study revealing pronounced resilience effects of HS014 on development of behavioral symptoms co-morbid with PTSD. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study

PubMed Central

Lahat, Eli; Goldman, Michael; Barr, Joseph; Bistritzer, Tzvi; Berkovitch, Matithyahu

2000-01-01

Objective To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. Design Prospective randomised study. Setting Paediatric emergency department in a general hospital. Subjects 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. Interventions Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). Main outcome measures Time from arrival at hospital to starting treatment and cessation of seizures. Results Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7.9 to 8.3). No significant side effects were observed in either group. Conclusion Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home. PMID:10884257

Impact of demographic and clinical parameters on video capsule transit time.

PubMed

Niv, Eva; Pinchasovich, Hadassa; Yanai, Henit

2016-10-01

Small bowel (SB) capsule endoscopy (CE) studies provide data on both gastric and SB transit times (GTT and SBTT, respectively). This study aimed to evaluate the influence of demographic and clinical parameters on the GTT and SBTT. Transit times for two generations of capsules (Pillcam SB2 and SB3) were also compared. Consecutive adult patients undergoing CE were included. GTT, SBTT, and cecum arrival rates were calculated and correlated to demographics and clinical characteristics. A total of 332 CE studies were analyzed. Neither GTT nor SBTT were impacted by age or sex. SBTT was prolonged in newly diagnosed Crohn's disease (CD) patients compared with all other patients (303.1±90.3 vs. 243.6±83.6 min, P=0.02 for SB2, 267.8±63 vs. 228.6±72.3, P=0.01 for SB3, respectively). Moreover, CD patients had higher incomplete study rates compared with patients with all other diagnoses (29.4 vs. 7.3%, respectively, P=0.0116) in the SB2 subgroup. Higher cecum arrival rates were achieved by the SB3 capsule compared with SB2 (97 vs. 91%, P=0.04). Patients with prolonged gastric time or patients with incomplete studies had similar demographic and clinical characteristics as others. Age and sex apparently do not influence intestinal kinetics. Newly diagnosed CD patients have relatively prolonged SBTTs. Demographic and clinical parameters cannot predict prolonged GTT or cecum nonarrival.

PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia.

PubMed

del Moral, Raimundo M G; Gómez-Morales, Mercedes; Hernández-Cortés, Pedro; Aguilar, David; Caballero, Trinidad; Aneiros-Fernández, Jose; Caba-Molina, Mercedes; Rodríguez-Martínez, M Dolores; Peralta, Andreina; Galindo-Moreno, Pablo; Osuna, Antonio; Oliver, F Javier; del Moral, Raimundo G; O'Valle, Francisco

2013-01-01

We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR) in kidneys preserved at 4°C in University of Wisconsin (UW) solution. Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0) knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ). We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

Autologous fibrin sealant reduces the incidence of prolonged air leak and duration of chest tube drainage after lung volume reduction surgery: a prospective randomized blinded study.

PubMed

Moser, C; Opitz, I; Zhai, W; Rousson, V; Russi, E W; Weder, W; Lardinois, D

2008-10-01

Prolonged air leak is reported in up to 50% of patients after lung volume reduction surgery. The effect of an autologous fibrin sealant on the intensity and duration of air leak and on the time to chest drain removal after lung volume reduction surgery was investigated in a randomized prospective clinical trial. Twenty-five patients underwent bilateral thoracoscopic lung volume reduction surgery. In each patient, an autologous fibrin sealant was applied along the staple lines on one side, whereas no additional measure was taken on the other side. Randomization of treatment was performed at the end of the resection on the first side. Air leak was assessed semiquantitatively by use of a severity score (0 = no leak; 4 = continuous severe leak) by two investigators blinded to the treatment. Mean value of the total severity scores for the first 48 hours postoperative was significantly lower in the treated group (4.7 +/- 7.7) than in the control group (16.0 +/- 10.1) (P < .001), independently of the length of the resection. Prolonged air leak and mean duration of drainage were also significantly reduced after application of the sealant (4.5% and 2.8 +/- 1.9 days versus 31.8% and 5.9 +/- 2.9 days) (P = .03 and P < .001). Autologous fibrin sealant for reinforcement of the staple lines after lung volume reduction surgery significantly reduces prolonged air leak and duration of chest tube drainage.

Influence of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing.

PubMed

Karimi, Zanyar; Allahyari, Teimour; Azghani, Mahmood Reza; Khalkhali, Hamidreza

2016-03-01

The present study was an attempt to investigate the effect of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing. Ten healthy subjects were recruited to stand for 2 h in three footwear conditions: barefoot, flat-bottomed shoe and unstable shoe. During standing, lower leg discomfort and EMG activity of medial gastrocnemius (MG) and tibialis anterior (TA) muscles were continuously monitored. Changes in lower leg volume over standing time also were measured. Lower leg discomfort rating reduced significantly while subjects standing on unstable shoe compared to the flat-bottomed shoe and barefoot condition. For lower leg volume, less changes also were observed with unstable shoe. The activity level and variation of right MG muscle was greater with unstable shoe compared to the other footwear conditions; however regarding the left MG muscle, significant difference was found between unstable shoe and flat-bottomed shoe only for activity level. Furthermore no significant differences were observed for the activity level and variation of TA muscles (right/left) among all footwear conditions. The findings suggested that prolonged standing with unstable footwear produces changes in lower leg muscles activity and leads to less volume changes. Perceived discomfort also was lower for this type of footwear and this might mean that unstable footwear can be used as ergonomic solution for employees whose work requires prolonged standing. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

PubMed Central

Dage, R.C.

1979-01-01

1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

Evaluation of mucociliary clearance among women using biomass and clean fuel in a periurban area of Chennai: A preliminary study

PubMed Central

Priscilla, Johnson; Padmavathi, Ramaswamy; Ghosh, Santu; Paul, Preetha; Ramadoss, Sitalakshmi; Balakrishnan, Kalpana; Thanasekaraan, Vijayalakshmi; Subhashini, A. S.

2011-01-01

Background: Nasal mucociliary clearance (NMC) plays a crucial role in the defense of the airways against inhaled substances and is affected by various factors. The effect of particulate matter on NMC in women using biomass fuel has not been well studied. Aim: This cross-sectional study was conducted to assess the NMC time in biomass fuel users and compare it with that of clean fuel users. Materials and Methods: NMC time and Peak Expiratory Flow Rate (PEFR) were determined in women of age ranging from 18 to 45 years using biomass fuel (n=30) and clean fuel (n=30). The time taken to perceive the sweet taste, following placement of saccharin 1 cm behind the anterior end of inferior turbinate was recorded as NMC time. PEFR was measured using mini-Wright peak flow meter. Comparison between groups was analyzed using t-test and ANOVA in R statistical software. Results: NMC time was significantly prolonged in biomass fuel users (765.8 ± 378.16 s) in comparison to clean fuel users (545.4 ± 215.55 s). PEFR was significantly reduced (319.3 l/min) in biomass fuel users compared to clean fuel users (371.7 l/min). Women from lower socioeconomic status, lower literacy status, older undernourished women and women cooking for>15 years had prolonged Saccharin Transit Time (STT) and reduced PEFR. Conclusions: This study highlights the effects of indoor air pollution on respiratory defense mechanism. This simple noninvasive, inexpensive, screening test can be used as an early indicator of respiratory damage caused by exposure to air pollutants. PMID:21654983

Effects of dietary caffeine on mood when rested and sleep restricted.

PubMed

James, Jack E; Gregg, M Elizabeth

2004-07-01

Prolonged use of caffeine can lead to physical dependence evidenced by characteristic withdrawal symptoms during abstinence. Debate exists as to whether mood enhancement by caffeine represents a net effect or merely the restoration of abstinence-induced mood decrements. One aim of this study was to determine the net effects on mood of dietary caffeine compared with prolonged abstinence. In addition, the study aimed to determine whether caffeine restores mood degraded by a non-caffeine source, namely, sleep restriction. A double-blind placebo-controlled cross-over design was employed in which 48 male and female volunteers alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested or sleep restricted. Mood was assessed using a computerized version of the profile of mood states (POMS), giving scores for overall mood and six mood dimensions. Gender had small effects on mood, whereas all mood dimensions were markedly adversely affected by sleep restriction. Caffeine had no significant net enhancing effects on mood when participants were rested, and produced no net restorative effects when mood was degraded by sleep restriction. On the contrary, caffeine-induced decrements in mood were observed during both conditions of rest and sleep restriction. Copyright 2004 John Wiley & Sons, Ltd.

The hemodynamic effects of prolonged respiratory alkalosis in anesthetized newborn piglets.

PubMed

Jundi, K; Barrington, K J; Henderson, C; Allen, R G; Finer, N N

2000-04-01

To test the hypothesis that prolonged alkalosis decreases cardiac output and, furthermore, exacerbates hypoxic pulmonary vasoconstriction, as respiratory alkalosis is frequently induced as a therapy for persistent pulmonary hypertension of the newborn despite a lack of controlled evidence of improved outcomes. Potential adverse effects of prolonged alkalosis have been demonstrated. Two groups (control, n = 6, and hypocapnic alkalosis, n = 6) of 1-3 day old fentanyl-anesthetized, vecuronium-paralyzed piglets were instrumented to measure cardiac index (CI) and mean systemic (MAP) and pulmonary (PAP) arterial pressures. Baseline values were recorded. Alveolar hypoxia was then induced to achieve an arterial oxygen saturation of between 50 and 60% for 15 min. Respiratory alkalosis was then induced, by increasing ventilation to achieve a pH between 7.55-7.60, and was continued for 240 min. Inspired carbon dioxide was used with hyperventilation in the control group to maintain pressure of arterial carbon dioxide (PaCO2) at 35-45 mmHg and pH of 7.35-7.45. Hypoxia was induced again at 15 and 240 min. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated. Prolonged alkalosis led to a significant and progressive fall in mean MAP from 61 (SD 7) mmHg at the start of the study falling to 50 (SD 6.9, p = 0.043), with no effect on CI. Calculated SVR decreased (0.45 SD 0.03 vs 0.36 SD 0.05). There were no statistically significant changes in any of the variables in the control group. Neither acute nor prolonged respiratory alkalosis had a significant effect on hypoxic pulmonary vasoconstriction. Prolonged hyperventilation leads to systemic hypotension, however it does not exacerbate hypoxic pulmonary vasoconstriction.

Effects of feeding lactobacillus GG on lethal irradiation in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, M.Y.; Chang, T.W.; Gorbach, S.L.

1987-05-01

Mice exposed to 1400 rads of total body irradiation experienced 80%-100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative bacteremia in these animals compared with controls.

Prolonged pain and disability are common after rib fractures.

PubMed

Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

2013-05-01

The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

DOE PAGES

Johannesen, Lars; Vicente, Jose; Hosseini, Meisam; ...

2016-12-30

Prolongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-T peakc (J-T peakc) and T peak-T end intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative). In this work, we describe an automated measurement methodology for assessment of the J-T peakcmore » and T peak-T end intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial. Comparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs. We have developed an automated algorithm for assessment of J-T peakc and T peak-T end intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. In conclusion, the algorithm is being released as open-source software.« less

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johannesen, Lars; Vicente, Jose; Hosseini, Meisam

Prolongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-T peakc (J-T peakc) and T peak-T end intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative). In this work, we describe an automated measurement methodology for assessment of the J-T peakcmore » and T peak-T end intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial. Comparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs. We have developed an automated algorithm for assessment of J-T peakc and T peak-T end intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. In conclusion, the algorithm is being released as open-source software.« less

An In Vivo Study of Low-Dose Intra-Articular Tranexamic Acid Application with Prolonged Clamping Drain Method in Total Knee Replacement: Clinical Efficacy and Safety.

PubMed

Sa-ngasoongsong, Paphon; Chanplakorn, Pongsthorn; Wongsak, Siwadol; Uthadorn, Krisorn; Panpikoon, Tanapong; Jittorntam, Paisan; Aryurachai, Katcharin; Angchaisukisiri, Pantap; Kawinwonggowit, Viroj

2015-01-01

Recently, combined intra-articular tranexamic acid (IA-TXA) injection with clamping drain method showed efficacy for blood loss and transfusion reduction in total knee replacement (TKR). However, until now, none of previous studies revealed the effect of this technique on pharmacokinetics, coagulation, and fibrinolysis. An experimental study was conducted, during 2011-2012, in 30 patients undergoing unilateral TKR. Patients received IA-TXA application and then were allocated into six groups regarding clamping drain duration (2-, 4-, 6-, 8-, 10-, and 12-hours). Blood and drainage fluid were collected to measure tranexamic acid (TXA) level and related coagulation and fibrinolytic markers. Postoperative complication was followed for one year. There was no significant difference of serum TXA level at 2 hour and 24 hour among groups (p < 0.05). Serum TXA level at time of clamp release was significantly different among groups with the highest level at 2 hour (p < 0.0001). There was no significant difference of TXA level in drainage fluid, postoperative blood loss, blood transfusion, and postoperative complications (p < 0.05). Low-dose IA-TXA application in TKR with prolonged clamping drain method is a safe and effective blood conservative technique with only minimal systemic absorption and without significant increase in systemic absorption over time.

Auditory evoked potentials in the auditory system of a beluga whale Delphinapterus leucas to prolonged sound stimuli.

PubMed

Popov, Vladimir V; Sysueva, Evgenia V; Nechaev, Dmitry I; Rozhnov, Vyatcheslav V; Supin, Alexander Ya

2016-03-01

The effects of prolonged (up to 1500 s) sound stimuli (tone pip trains) on evoked potentials (the rate following response, RFR) were investigated in a beluga whale. The stimuli (rhythmic tone pips) were of frequencies of 45, 64, and 90 kHz at levels from 20 to 60 dB above threshold. Two experimental protocols were used: short- and long-duration. For the short-duration protocol, the stimuli were 500-ms-long pip trains that repeated at a rate of 0.4 trains/s. For the long-duration protocol, the stimuli were continuous pip successions lasting up to 1500 s. The RFR amplitude gradually decreased by three to seven times from 10 ms to 1500 s of stimulation. Decrease of response amplitude during stimulation was approximately proportional to initial (at the start of stimulation) response amplitude. Therefore, even for low stimulus level (down to 20 dB above the baseline threshold) the response was never suppressed completely. The RFR amplitude decay that occurred during stimulation could be satisfactorily approximated by a combination of two exponents with time constants of 30-80 ms and 3.1-17.6 s. The role of adaptation in the described effects and the impact of noise on the acoustic orientation of odontocetes are discussed.

In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig.

PubMed

Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B; Grunnet, Morten

2008-07-01

The long QT syndrome is characterized by a prolongation of the QT interval measured on the surface electrocardiogram. Prolonging the QT interval increases the risk of dangerous ventricular fibrillations, eventually leading to sudden cardiac death. Pharmacologically induced QT interval prolongations are most often caused by antagonizing effects on the repolarizing cardiac current called IKr. In humans IKr is mediated by the human ether-a-go-go related gene (hERG) potassium channel. We recently presented NS3623, a compound that selectively activates this channel. The present study was dedicated to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a hERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically induced QT prolongation in both anaesthetized and conscious guinea pigs.

No effect of isolated long-term supine immobilization or profound prolonged hypoxia on blood coagulation.

PubMed

Venemans-Jellema, A; Schreijer, A J M; Le Cessie, S; Emmerich, J; Rosendaal, F R; Cannegieter, S C

2014-06-01

Long-distance air travel is associated with an increased risk of venous thrombosis. The most obvious factor that can explain air travel-related thrombosis is prolonged seated immobilization. In addition, hypobaric hypoxia has been shown to affect coagulation, and the lowered atmospheric pressures present in the cabin during the flight may therefore play an etiologic role. Because immobilization and hypoxic conditions are usually present simultaneously in airplanes or hypobaric chambers, their separate effects on the coagulation system or on thrombosis risk have not been studied extensively. To investigate the separate effects of long-term immobilization and profound prolonged hypoxia on blood coagulation. We performed two studies in collaboration with European Space Agency/European Space Research and Technology Centre. In the first study, 24 healthy, non-smoking, adult women underwent 60 days of -6° head-down bed rest. In the second study, we took blood samples from 25 healthy men who participated during their stay in the Concordia station in Antarctica, where, due to the atmospheric conditions, continuous severe hypobaric hypoxia is present. In both studies, we measured markers of blood coagulation at baseline and at several time points during the exposures. We observed no increase in coagulation markers during immobilization or in the hypobaric environment, compared with baseline measurements. Our results indicate that neither immobilization nor hypoxia per se affects blood coagulation. These results implicate that a combination of risk factors is necessary to induce the coagulation system during air travel. © 2014 International Society on Thrombosis and Haemostasis.

The cost-effectiveness of psychotherapy for the major psychiatric diagnoses.

PubMed

Lazar, Susan G

2014-09-01

Psychotherapy is an effective and often highly cost-effective medical intervention for many serious psychiatric conditions. Psychotherapy can also lead to savings in other medical and societal costs. It is at times the firstline and most important treatment and at other times augments the efficacy of psychotropic medication. Many patients are in need of more prolonged and intensive psychotherapy, including those with personality disorders and those with chronic complex psychiatric conditions often with severe anxiety and depression. Many patients with serious and complex psychiatric illness have experienced severe early life trauma in an atmosphere in which family members or caretakers themselves have serious psychiatric disorders. Children and adolescents with learning disabilities and those with severe psychiatric disorders can also require more than brief treatment. Other diagnostic groups for whom psychotherapy is effective and cost-effective include patients with schizophrenia, anxiety disorders (including posttraumatic stress disorder), depression, and substance abuse. In addition, psychotherapy for the medically ill with concomitant psychiatric illness often lowers medical costs, improves recovery from medical illness, and at times even prolongs life compared to similar patients not given psychotherapy. While "cost-effective" treatments can yield savings in healthcare costs, disability claims, and other societal costs, "cost-effective" by no means translates to "cheap" but instead describes treatments that are clinically effective and provided at a cost that is considered reasonable given the benefit they provide, even if the treatments increase direct expenses. In the current insurance climate in which Mental Health Parity is the law, insurers nonetheless often use their own non-research and non-clinically based medical necessity guidelines to subvert it and limit access to appropriate psychotherapeutic treatments. Many patients, especially those who need extended and intensive psychotherapy, are at risk of receiving substandard care due to inadequate insurance reimbursement. These patients remain vulnerable to residual illness and the concomitant sequelae in lost productivity, dysfunctional interpersonal and family relationships, comorbidity including increased medical and surgical services, and increased mortality.

Prolonged self-paced exercise in the heat – environmental factors affecting performance

PubMed Central

Junge, Nicklas; Jørgensen, Rasmus; Flouris, Andreas D.; Nybo, Lars

2016-01-01

ABSTRACT In this review we examine how self-paced performance is affected by environmental heat stress factors during cycling time trial performance as well as considering the effects of exercise mode and heat acclimatization. Mean power output during prolonged cycling time trials in the heat (≥30°C) was on average reduced by 15% in the 14 studies that fulfilled the inclusion criteria. Ambient temperature per se was a poor predictor of the integrated environmental heat stress and 2 of the prevailing heat stress indices (WBGT and UTCI) failed to predict the environmental influence on performance. The weighing of wind speed appears to be too low for predicting the effect for cycling in trained acclimatized subjects, where performance may be maintained in outdoor time trials at ambient temperatures as high as 36°C (36°C UTCI; 28°C WBGT). Power output during indoor trials may also be maintained with temperatures up to at least 27°C when humidity is modest and wind speed matches the movement speed generated during outdoor cycling, whereas marked reductions are observed when air movement is minimal. For running, representing an exercise mode with lower movement speed and higher heat production for a given metabolic rate, it appears that endurance is affected even at much lower ambient temperatures. On this basis we conclude that environmental heat stress impacts self-paced endurance performance. However, the effect is markedly modified by acclimatization status and exercise mode, as the wind generated by the exercise (movement speed) or the environment (natural or fan air movement) exerts a strong influence. PMID:28090557

Analysis of Radiation Effects in Digital Subtraction Angiography of Intracranial Artery Stenosis.

PubMed

Guo, Chaoqun; Shi, Xiaolei; Ding, Xianhui; Zhou, Zhiming

2018-04-21

Intracranial artery stenosis (IAS) is the most common cause for acute cerebral accidents. Digital subtraction angiography (DSA) is the gold standard to detect IAS and usually brings excess radiation exposure to examinees and examiners. The artery pathology might influence the interventional procedure, causing prolonged radiation effects. However, no studies on the association between IAS pathology and operational parameters are available. A retrospective analysis was conducted on 93 patients with first-ever stroke/transient ischemic attack, who received DSA examination within 3 months from onset in this single center. Comparison of baseline characteristics was determined by 2-tailed Student's t-test or the chi-square test between subjects with and without IAS. A binary logistic regression analysis was performed to determine the association between IAS pathology and the items with a P value <0.05 in Student's t-test or chi-square test. There were 93 candidates (42 with IAS and 51 without IAS) in this study. The 2 groups shared no significance of the baseline characteristics (P > 0.05). We found a significantly higher total time, higher kerma area product, greater total dose, and greater DSA dose in the IAS group than in those without IAS (P < 0.05). A binary logistic regression analysis indicated the significant association between total time and IAS pathology (P < 0.05) but no significance in kerma area product, radiation dose, and DSA dose (P > 0.05). IAS pathology would indicate a prolonged total time of DSA procedure in clinical practice. However, the radiation effects would not change with pathologic changes. Copyright © 2018 Elsevier Inc. All rights reserved.

Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis.

PubMed

Fiene, Marina; Rufener, Katharina S; Kuehne, Maria; Matzke, Mike; Heinze, Hans-Jochen; Zaehle, Tino

2018-03-01

Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.

Sublethal effects of four insecticides on folding and spinning behavior in the rice leaffolder, Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae).

PubMed

Yang, Yajun; Wang, Caiyun; Xu, Hongxing; Lu, Zhongxian

2018-03-01

The rice leaffolder, Cnaphalocrocis medinalis, is an important rice pest. The sublethal effects of chlorpyrifos, chlorantraniliprole, emamectin benzoate and spinosad were investigated on the folding and spinning behaviors of third- to fifth-instar C. medinalis larvae (L3 - L5) after insecticidal exposure of the second instar. A 25% lethal concentration (LC 25 ) of chlorpyrifos prolonged the leaf selection time of L5, and reduced the number of binds per primary fold for L4 and L5. An LC 10 of chlorantraniliprole reduced the number of binds per primary fold for L4 and increased the number of head swings per bind for L5. An LC 10 of emamectin benzoate shortened the primary fold length for L5 and decreased the number of head swings per primary fold for L3 and L4 and the number of head swings per bind for L3, while an LC 25 of emamectin benzoate shortened the fold length per 24 h for L5 and folding time for L3. An LC 10 of spinosad lowered the fold length per 24 h and the number of head swings for L5. An LC 25 of spinosad prolonged leaf selection time, and decreased primary fold length, binds per primary fold, binds per fold and fold length per 24 h in L5. Emamectin benzoate and spinosad exerted stronger sublethal effects on the folding and spinning behavior of C. medinalis than chlorpyrifos and chlorantraniliprole. These results provide better understanding of the sublethal effects of interactions of insecticides on C. medinalis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Cyclic AMP-elevating Agents Promote Cumulus Cell Survival and Hyaluronan Matrix Stability, Thereby Prolonging the Time of Mouse Oocyte Fertilizability*

PubMed Central

Di Giacomo, Monica; Camaioni, Antonella; Klinger, Francesca G.; Bonfiglio, Rita; Salustri, Antonietta

2016-01-01

Cumulus cells sustain the development and fertilization of the mammalian oocyte. These cells are retained around the oocyte by a hyaluronan-rich extracellular matrix synthesized before ovulation, a process called cumulus cell-oocyte complex (COC) expansion. Hyaluronan release and dispersion of the cumulus cells progressively occur after ovulation, paralleling the decline of oocyte fertilization. We show here that, in mice, postovulatory changes of matrix are temporally correlated to cumulus cell death. Cumulus cell apoptosis and matrix disassembly also occurred in ovulated COCs cultured in vitro. COCs expanded in vitro with FSH or EGF underwent the same changes, whereas those expanded with 8-bromo-adenosine-3′,5′-cyclic monophosphate (8-Br-cAMP) maintained integrity for a longer time. It is noteworthy that 8-Br-cAMP treatment was also effective on ovulated COCs cultured in vitro, prolonging the vitality of the cumulus cells and the stability of the matrix from a few hours to >2 days. Stimulation of endogenous adenylate cyclase with forskolin or inhibition of phosphodiesterase with rolipram produced similar effects. The treatment with selective cAMP analogues suggests that the effects of cAMP elevation are exerted through an EPAC-independent, PKA type II-dependent signaling pathway, probably acting at the post-transcriptional level. Finally, overnight culture of ovulated COCs with 8-Br-cAMP significantly counteracted the decrease of fertilization rate, doubling the number of fertilized oocytes compared with control conditions. In conclusion, these studies suggest that cAMP-elevating agents prevent cumulus cell senescence and allow them to continue to exert beneficial effects on oocyte and sperm, thereby extending in vitro the time frame of oocyte fertilizability. PMID:26694612

Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment

PubMed Central

Breen, Des; Wilmer, Alexander; Bodenham, Andrew; Bach, Vagn; Bonde, Jan; Kessler, Paul; Albrecht, Sven; Shaikh, Soraya

2004-01-01

Introduction This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care. Methods A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance ≥ 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6–9 μg/kg per hour), with propofol administered if required, to achieve a target Sedation–Agitation Scale score of 2–4, with no or mild pain. Results There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use. Conclusion Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours. PMID:14975051

Pharmacokinetics and anesthetic and cardiopulmonary effects of propofol in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).

PubMed

Hawkins, Michelle G; Wright, Bonnie D; Pascoe, Peter J; Kass, Philip H; Maxwell, Lara K; Tell, Lisa A

2003-06-01

To determine induction doses, anesthetic constant rate infusions (CRI), and cardiopulmonary effects of propofol in red-tailed hawks and great horned owls and propofol pharmacokinetics in the owls during CRI. 6 red-tailed hawks and 6 great horned owls. The CRI dose necessary for a loss of withdrawal reflex was determined via specific stimuli. Anesthesia was induced by IV administration of propofol (1 mg/kg/min) and maintained by CRI at the predetermined dose for 30 minutes. Heart and respiratory rates, arterial blood pressures, and blood gas tensions were obtained in awake birds and at various times after induction. End-tidal CO2 (ETCO2) concentration and esophageal temperature were obtained after induction. Propofol plasma concentrations were obtained after induction and after completion of the CRI in the owls. Recovery times were recorded. Mean +/- SD doses for induction and CRI were 4.48 +/- 1.09 mg/kg and 0.48 +/- 0.06 mg/kg/min, respectively, for hawks and 3.36 +/- 0.71 mg/kg and 0.56 +/- 0.15 mg/kg/min, respectively, for owls. Significant increases in PaCO2, HCO3, and ETCO2 in hawks and owls and significant decreases in arterial pH in hawks were detected. A 2-compartment model best described the owl pharmacodynamic data. Recovery times after infusion were prolonged and varied widely. Central nervous system excitatory signs were observed during recovery. Effects on blood pressure were minimal, but effective ventilation was reduced, suggesting the need for careful monitoring during anesthesia. Prolonged recovery periods with moderate-to-severe excitatory CNS signs may occur in these species at these doses.

Colour Evaluation, Bioactive Compound Content, Phenolic Acid Profiles and in Vitro Biological Activity of Passerina del Frusinate White Wines: Influence of Pre-Fermentative Skin Contact Times.

PubMed

Carbone, Katya; Fiordiponti, Luciano

2016-07-22

Passerina del Frusinate is an autochthonous wine grape variety, which grows in the Lazio region that is currently being evaluated by local wine producers. In this study, colour properties (CIELab coordinates), bioactive compounds (total polyphenols and flavan-3-ols), HPLC-DAD phenolic acid profiles and in vitro biological activity of monovarietal Passerina del Frusinate white wines and the effect of different maceration times (0, 18 and 24 h) were evaluated based on these parameters. Results highlighted statistically significant differences for almost all analysed parameters due to a strong influence of the pre-fermentative skin contact time. The flavan content of macerated wines was six times higher than that of the control, while total polyphenols were 1.5 times higher. According to their phytochemical content, macerated wines showed the highest antiradical capacity tested by means of DPPH(•) and ABTS(+•) assays. Besides, prolonged maceration resulted in a reduction of CIELab coordinates as well as of the content of phenolic substances and antiradical capacity. Among the phenolic acids analysed, the most abundant were vanillic acid and caffeic acid; the latter proved to be the most susceptible to degradation as a result of prolonged maceration. Passerina del Frusinate appears as a phenol-rich white wine with a strong antioxidant potential similar to that of red wines.

Effects on respiratory homeostasis of prolonged, continuous hyperoxia at 1.5 to 3.0 ATA in man in Predictive Studies V

NASA Technical Reports Server (NTRS)

Gelfand, R.; Clark, J. M.; Lambertsen, C. J.; Pisarello, J. B.

1987-01-01

Prolonged exposures of men to continuous hyperoxia at 3.0, 2.5, 2.0, and 1.5 ATA were conducted to define CNS oxygen tolerance and to investigate the effects of prolonged hyperoxia on CNS and other organ functions. Altered respiratory homeostasis was evident during exposures of men to 2.5 and 3.0 ATA O2 as nonprogressive increment in ventilation and reciprocal decrement in PET(CO2). These changes were progressive during exposure at 1.5 ATA O2. Mean values of respiratory reactivity at CO2 were somewhat increased following prolonged hyperoxia at 1.5 and 2.5 ATA, compared to preexposure mean values. Hypoxic ventilatory response was unchanged or enhanced after oxygen exposures at 1.5 and 2.5 ATA. Observed respiratory and body temperature changes were not of sufficient magnitude to impair function.

Drained coastal peatlands: A potential nitrogen source to marine ecosystems under prolonged drought and heavy storm events-A microcosm experiment.

PubMed

Wang, Hongjun; Richardson, Curtis J; Ho, Mengchi; Flanagan, Neal

2016-10-01

Over the past several decades there has been a massive increase in coastal eutrophication, which is often caused by increased runoff input of nitrogen from landscape alterations. Peatlands, covering 3% of land area, have stored about 12-21% of global soil organic nitrogen (12-20Pg N) around rivers, lakes and coasts over millennia and are now often drained and farmed. Their huge nitrogen pools may be released by intensified climate driven hydrologic events-prolonged droughts followed by heavy storms-and later transported to marine ecosystems. In this study, we collected peat monoliths from drained, natural, and restored coastal peatlands in the Southeastern U.S., and conducted a microcosm experiment simulating coupled prolonged-drought and storm events to (1) test whether storms could trigger a pulse of nitrogen export from drought-stressed peatlands and (2) assess how differentially hydrologic managements through shifting plant communities affect nitrogen export by combining an experiment of nitrogen release from litter. During the drought phase, we observed a significant temporal variation in net nitrogen mineralization rate (NMR). NMR spiked in the third month and then decreased rapidly. This pattern indicates that drought duration significantly affects nitrogen mineralization in peat. NMR in the drained site reached up to 490±110kgha(-1)year(-1), about 5 times higher than in the restored site. After the 14-month drought phase, we simulated a heavy storm by bringing peat monoliths to saturation. In the discharge waters, concentrations of total dissolved nitrogen in the monoliths from the drained site (72.7±16.3mgL(-1)) was about ten times as high as from the restored site. Our results indicate that previously drained peatlands under prolonged drought are a potent source of nitrogen export. Moreover, drought-induced plant community shifts to herbaceous plants substantially raise nitrogen release with lasting effects by altering litter quality in peatlands. Copyright © 2016 Elsevier B.V. All rights reserved.

Neosaxitoxin in Rat Sciatic Block: Improved Therapeutic Index Using Combinations with Bupivacaine, with and without Epinephrine.

PubMed

Templin, Jay S; Wylie, Matthew C; Kim, Joseph D; Kurgansky, Katherine E; Gorski, Grzegorz; Kheir, John; Zurakowski, David; Corfas, Gabriel; Berde, Charles

2015-10-01

Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker undergoing clinical trials as a prolonged-duration local anesthetic. Rat sciatic block and intravenous infusion models were used to assess efficacy and local and systemic toxicities for NeoSTX in saline (NeoSTX-Saline), bupivacaine (Bup), and their combination (NeoSTX-Bup). Exploratory studies evaluated the effects of addition of epinephrine to NeoSTX-Bup (NeoSTX-Bup-Epi). Rats received percutaneous sciatic blocks with escalating doses of NeoSTX-Saline or NeoSTX-Bup. Sensory-nocifensive block was assessed using modified hotplate and Von Frey filaments. Motor-proprioceptive function was assessed by extensor postural thrust. Nerves were examined histologically after 7 days and scored on the Estebe-Myers scale. Median lethal dose was estimated for NeoSTX-Saline and in combinations. Accidental intravenous overdose was simulated in isoflurane-anesthetized, spontaneously breathing rats receiving NeoSTX-Saline (n = 6), Bup (n = 7), or NeoSTX-Bup (n = 13), with respiratory, hemodynamic, and electrocardiographic endpoints. Additional groups received blocks with NeoSTX-Bup-Epi (n = 80). Investigators were blinded for behavioral and histologic studies. NeoSTX-Bup produced more prolonged sensory and motor block compared with NeoSTX-Saline or Bup. NeoSTX-Bup-Epi further prolonged median time to near-complete recovery for 3 μg/kg NeoSTX-Bup (hotplate: 48 vs. 6 h, P < 0.001). With sciatic injections, addition of Bup did not worsen the systemic toxicity (median lethal dose) compared with NeoSTX-Saline. Intravenous NeoSTX-Saline infusion had significantly longer times to apnea, first arrhythmia, and asystole compared with Bup (P < 0.001 for each). Histologic injury scores overall were low for all groups, with median scores of 0 (interquartile range, 0 to 0) on a 5-point scale. NeoSTX-Bup and NeoSTX-Bup-Epi hold promise for prolonged-duration local anesthesia.

Regional effects of streptozotocin-induced diabetes on shortening and calcium transport in epicardial and endocardial myocytes from rat left ventricle.

PubMed

Smail, Manal M A; Qureshi, Muhammad A; Shmygol, Anatoliy; Oz, Murat; Singh, Jaipaul; Sydorenko, Vadym; Arabi, Alya; Howarth, Frank C; Al Kury, Lina

2016-11-01

In the heart, the left ventricle pumps blood at higher pressure than the right ventricle. Within the left ventricle, the electromechanical properties of ventricular cardiac myocytes vary transmurally and this may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. Diabetes is also associated with alterations in hemodynamic function. The aim of this study was to investigate shortening and Ca 2+ transport in epicardial (EPI) and endocardial (ENDO) left ventricular myocytes in the streptozotocin (STZ)-induced diabetic rat. Shortening, intracellular Ca 2+ and L-type Ca 2+ current (I Ca,L ) were measured by video detection, fura-2 microfluorimetry, and whole-cell patch clamp techniques, respectively. Time to peak (TPK) shortening was prolonged to similar extents in ENDO and EPI myocytes from STZ-treated rats compared to ENDO and EPI myocytes from controls. Time to half (THALF) relaxation of shortening was prolonged in ENDO myocytes from STZ-treated rats compared to ENDO controls. TPK Ca 2+ transient was prolonged in ENDO myocytes from STZ-treated rats compared to ENDO controls. THALF decay of the Ca 2+ transient was prolonged in ENDO myocytes from STZ-treated rats compared to ENDO controls. Sarcoplasmic reticulum (SR) fractional release of Ca 2+ was reduced in EPI myocytes from STZ-treated rats compared to EPI controls. I C a,L activation, inactivation, and recovery from inactivation were not significantly altered in EPI and ENDO myocytes from STZ-treated rats or controls. Regional differences in Ca 2+ transport may partly underlie differences in ventricular myocyte shortening across the wall of the healthy and the STZ-treated rat left ventricle. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

The effectiveness of apneic oxygenation during tracheal intubation in various clinical settings: a narrative review.

PubMed

Wong, David T; Yee, Amanda J; Leong, Siaw May; Chung, Frances

2017-04-01

During the process of tracheal intubation, patients are apneic or hypoventilating and are at risk of becoming hypoxemic. This risk is especially high in patients with acute or chronic respiratory failure and accompanying compromised respiratory reserve. To address this concern, apneic oxygenation can be administered during tracheal intubation to aid in maintaining arterial oxygen saturation. The objective of this narrative review is to examine the utilization of apneic oxygenation within the operating room, intensive care unit (ICU), emergency department, and pre-hospital settings and to determine its efficacy compared with controls. For this narrative review, we obtained pertinent articles using MEDLINE ® (1946 to April 2016), EMBASE™ (1974 to April 2016), Google Scholar, and manual searches. Apneic oxygenation was administered using various techniques, including the use of nasal prongs, nasopharyngeal or endotracheal catheters, or laryngoscopes. First, all 12 operating room studies showed that apneic oxygenation significantly prolonged the duration to, and incidence of, desaturation. Second, two of the five ICU studies showed a significantly smaller decline in oxygen saturation with apneic oxygenation, with three studies showing no statistically significant difference vs controls. Lastly, two emergency department or pre-hospital studies showed that the use of apneic oxygenation resulted in a significantly lower incidence of desaturation and smaller declines in oxygen saturation. Sixteen of the 19 studies showed that apneic oxygenation prolongs safe apneic time and reduces the incidence of arterial oxygen desaturation. Overall, studies in this review show that apneic oxygenation prolongs the time to oxygen desaturation during tracheal intubation. Nevertheless, the majority of the studies were small in size, and they neither measured nor were adequately powered to detect adverse respiratory events or other serious rare complications. Prolonged apneic oxygenation (with its consequent hypercarbia) can have risks and should be avoided in patients with conditions such as increased intracranial pressure, metabolic acidosis, hyperkalemia, and pulmonary hypertension.

Which is your choice for prolonging the analgesic duration of single-shot interscalene brachial blocks for arthroscopic shoulder surgery? intravenous dexamethasone 5 mg vs. perineural dexamethasone 5 mg randomized, controlled, clinical trial.

PubMed

Chun, Eun Hee; Kim, Youn Jin; Woo, Jae Hee

2016-06-01

The aim of this study was to compare the effect of intravenous (I.V.) dexamethasone with that of perineural dexamethasone on the prolongation of analgesic duration of single-shot interscalene brachial plexus blocks (SISB) in patients undergoing arthroscopic shoulder surgery. We performed a prospective, randomized, double-blind, placebo-controlled study. Patients undergoing elective arthroscopic shoulder surgery with ultrasound-guided SISB were enrolled and randomized into 2 groups. A total volume of 12 mL of the study drug was prepared with a final concentration of 0.5% ropivacaine. In the I.V. group, patients received SISB using ropivacaine 5 mg mL with normal saline (control) with dexamethasone 5 mg I.V. injection. In the perineural group, patients received SISB using ropivacaine 5 mg mL with dexamethasone 5 mg, with normal saline 1 mL I.V. injection. The primary outcome was the time to the first analgesic request, defined as the time between the end of the operation and the first request of analgesics by the patient. The secondary outcomes included patient satisfaction scores, side effects, and neurological symptoms. Patients were randomly assigned to 1 of the 2 groups using a computer-generated randomization table. An anesthesiologist blinded to the group assignments prepared the solutions for injection. The patients and the investigator participating in the study were also blinded to the group assignments. One hundred patients were randomized. Data were analyzed for 99 patients. One case in the I.V. group was converted to open surgery and was therefore not included in the study. Perineural dexamethasone significantly prolonged analgesic duration (median, standard error: 1080 minutes, 117.5 minutes) compared with I.V. dexamethasone (810 minutes, 48.1 minutes) (P = 0.02). There were no significant differences in side effects, neurological symptoms, or changes in blood glucose values between the 2 groups. Our results show that perineural dexamethasone 5 mg is more effective than I.V. dexamethasone 5 mg with regard to analgesic duration of SISB for arthroscopic shoulder surgery.

Protective Effect of Different Anti-Rabies Virus VHH Constructs against Rabies Disease in Mice

PubMed Central

Terryn, Sanne; Francart, Aurélie; Lamoral, Sophie; Hultberg, Anna; Rommelaere, Heidi; Wittelsberger, Angela; Callewaert, Filip; Stohr, Thomas; Meerschaert, Kris; Ottevaere, Ingrid; Stortelers, Catelijne; Vanlandschoot, Peter; Kalai, Michael; Van Gucht, Steven

2014-01-01

Rabies virus causes lethal brain infection in about 61000 people per year. Each year, tens of thousands of people receive anti-rabies prophylaxis with plasma-derived immunoglobulins and vaccine soon after exposure. Anti-rabies immunoglobulins are however expensive and have limited availability. VHH are the smallest antigen-binding functional fragments of camelid heavy chain antibodies, also called Nanobodies. The therapeutic potential of anti-rabies VHH was examined in a mouse model using intranasal challenge with a lethal dose of rabies virus. Anti-rabies VHH were administered directly into the brain or systemically, by intraperitoneal injection, 24 hours after virus challenge. Anti-rabies VHH were able to significantly prolong survival or even completely rescue mice from disease. The therapeutic effect depended on the dose, affinity and brain and plasma half-life of the VHH construct. Increasing the affinity by combining two VHH with a glycine-serine linker into bivalent or biparatopic constructs, increased the neutralizing potency to the picomolar range. Upon direct intracerebral administration, a dose as low as 33 µg of the biparatopic Rab-E8/H7 was still able to establish an anti-rabies effect. The effect of systemic treatment was significantly improved by increasing the half-life of Rab-E8/H7 through linkage with a third VHH targeted against albumin. Intraperitoneal treatment with 1.5 mg (2505 IU, 1 ml) of anti-albumin Rab-E8/H7 prolonged the median survival time from 9 to 15 days and completely rescued 43% of mice. For comparison, intraperitoneal treatment with the highest available dose of human anti-rabies immunoglobulins (65 mg, 111 IU, 1 ml) only prolonged survival by 2 days, without rescue. Overall, the therapeutic benefit seemed well correlated with the time of brain exposure and the plasma half-life of the used VHH construct. These results, together with the ease-of-production and superior thermal stability, render anti-rabies VHH into valuable candidates for development of alternative post exposure treatment drugs against rabies. PMID:25347556

Sprint training shortens prolonged action potential duration in postinfarction rat myocyte: mechanisms.

PubMed

Zhang, X Q; Zhang, L Q; Palmer, B M; Ng, Y C; Musch, T I; Moore, R L; Cheung, J Y

2001-05-01

Two electrophysiological manifestations of myocardial infarction (MI)-induced myocyte hypertrophy are prolongation of action potential duration (APD) and reduction of transient outward current (I(to)) density. Because high-intensity sprint training (HIST) ameliorated myocyte hypertrophy and improved myocyte Ca(2+) homeostasis and contractility after MI, the present study evaluated whether 6-8 wk of HIST would shorten the prolonged APD and improve the depressed I(to) in post-MI myocytes. There were no differences in resting membrane potential and action potential amplitude (APA) measured in myocytes isolated from sham-sedentary (Sed), MI-Sed, and MI-HIST groups. Times required for repolarization to 50 and 90% APA were significantly (P < 0.001) prolonged in MI-Sed myocytes. HIST reduced times required for repolarization to 50 and 90% APA to values observed in Sham-Sed myocytes. The fast and slow components of I(to) were significantly (P < 0.0001) reduced in MI-Sed myocytes. HIST significantly (P < 0.001) enhanced the fast and slow components of I(to) in MI myocytes, although not to levels observed in Sham-Sed myocytes. There were no significant differences in steady-state I(to) inactivation and activation parameters among Sham-Sed, MI-Sed, and MI-HIST myocytes. Likewise, recovery from time-dependent inactivation was also similar among the three groups. We suggest that normalization of APD after MI by HIST may be mediated by restoration of I(to) toward normal levels.

Course of Weaning from Prolonged Mechanical Ventilation after Cardiac Surgery

PubMed Central

Herlihy, James P.; Koch, Stephen M.; Jackson, Robert; Nora, Hope

2006-01-01

In order to determine the temporal pattern of weaning from mechanical ventilation for patients undergoing prolonged mechanical ventilation after cardiac surgery, we performed a retrospective review of 21 patients' weaning courses at our long-term acute care hospital. Using multiple regression analysis of an estimate of individual patients' percentage of mechanical ventilator support per day (%MVSD), we determined that 14 of 21 patients (67%) showed a statistically significant quadratic or cubic relationship between time and %MVSD. These patients showed little or no improvement in their ventilator dependence until a point in time when, abruptly, they began to make rapid progress (a “wean turning point”), after which they progressed to discontinuation of mechanical ventilation in a relatively short period of time. The other 7 patients appeared to have a similar weaning pattern, although the data were not statistically significant. Most patients in the study group weaned from the ventilator through a specific temporal pattern that is newly described herein. Data analysis suggested that the mechanism for the development of a wean turning point was improvement of pulmonary mechanics rather than improvement in gas exchange or respiratory load. Although these observations need to be confirmed by a prospective trial, they may have implications for weaning cardiac surgery patients from prolonged mechanical ventilation, and possibly for weaning a broader group of patients who require prolonged mechanical ventilation. PMID:16878611

Development of bupivacaine decorated reduced graphene oxide and its local anesthetic effect-In vivo study.

PubMed

Zhang, Zhi; Zhang, Xin; Li, Aixiang; Ma, Chuangen

2018-03-01

The present works aims to develop bupivacaine modified reduced graphene oxide (BPV/RGO), and comparative evaluation of their anesthetic effect with free bupivacaine (BPV). The prepared BPV/RGO was studied by using various spectroscopic and microscopic characterization studies. In vitro drug release from BPV/RGO was studied using HPLC analysis. The cytotoxicity of BPV/RGO was studied against fibroblast (3T3) cells. In vivo evaluation of anesthetic effects was performed on animal models. BPV/RGO showed a prolonged in vitro release and lower cytotoxicity when compared to free BPV. Also, BPV/RGO showed a significantly prolonged analgesic effect when compared to free BPV. Further, the prepared BPV/RGO drug delivery system demonstrated to function as gifted to overcome the drawbacks of free BPV and other available drug delivery systems by prolonging the anesthetic effect with poor cytotoxicity. Copyright © 2018. Published by Elsevier B.V.

Study of Sedative-Hypnotic Effects of Aloe vera L. Aqueous Extract through Behavioral Evaluations and EEG Recording in Rats

PubMed Central

Abdollahnejad, Fatemeh; Mosaddegh, Mahmoud; Nasoohi, Sanaz; Mirnajafi-Zadeh, Javad; Kamalinejad, Mohammad; Faizi, Mehrdad

2016-01-01

In this study, we investigated the sedative and hypnotic effects of the aqueous extract of Aloe vera on rats. In order to evaluate the overall hypnotic effects of the Aloe vera extract, open field and loss of righting reflex tests were primarily used. The sedative and hypnotic effects of the extract were then confirmed by detection of remarkable raise in the total sleeping time through analysis of electroencephalographic (EEG) recordings of animals. Analysis of the EEG recordings showed that there is concomitant change in Rapid Eye Movement (REM) and None Rapid Eye Movement (NREM) sleep in parallel with the prolonged total sleeping time. Results of the current research show that the extract has sedative-hypnotic effects on both functional and electrical activities of the brain. PMID:27610170

Reading Time as Evidence for Mental Models in Understanding Physics

NASA Astrophysics Data System (ADS)

Brookes, David T.; Mestre, José; Stine-Morrow, Elizabeth A. L.

2007-11-01

We present results of a reading study that show the usefulness of probing physics students' cognitive processing by measuring reading time. According to contemporary discourse theory, when people read a text, a network of associated inferences is activated to create a mental model. If the reader encounters an idea in the text that conflicts with existing knowledge, the construction of a coherent mental model is disrupted and reading times are prolonged, as measured using a simple self-paced reading paradigm. We used this effect to study how "non-Newtonian" and "Newtonian" students create mental models of conceptual systems in physics as they read texts related to the ideas of Newton's third law, energy, and momentum. We found significant effects of prior knowledge state on patterns of reading time, suggesting that students attempt to actively integrate physics texts with their existing knowledge.

Extensive deep vein thrombosis following prolonged gaming ('gamer's thrombosis'): a case report.

PubMed

Chang, Hsien-Cheng Leon; Burbridge, Hayley; Wong, Conroy

2013-10-08

The average time spent playing video games is increasing. Prolonged immobility associated with gaming may therefore be an important risk factor for venous thromboembolism. We report a case of deep vein thrombosis associated with prolonged playing of PlayStation® games. A 31-year-old Caucasian man, an exterior painter, presented with a three-day history of left leg pain and swelling after playing PlayStation® games for almost eight hours a day for four consecutive days. Doppler ultrasound of the left leg confirmed extensive left leg deep venous thrombosis requiring thrombolysis and anticoagulation. Video gaming should be considered a risk factor for venous thromboembolism. Further studies are needed to estimate the degree of risk associated with prolonged periods of playing video games, and education for preventing venous thrombosis should be provided to gamers.

Reversal of muscle atrophy by Zhimu and Huangbai herb pair via activation of IGF-1/Akt and autophagy signal in cancer cachexia.

PubMed

Zhuang, Pengwei; Zhang, Jinbao; Wang, Yan; Zhang, Mixia; Song, Lili; Lu, Zhiqiang; Zhang, Lu; Zhang, Fengqi; Wang, Jing; Zhang, Yanjun; Wei, Hongjun; Li, Hongyan

2016-03-01

Muscle atrophy is the prominent clinical feature of cancer-induced cachexia. Zhimu and Huangbai herb pair (ZBHP) has been used since ancient China times and have been phytochemically investigated for constituents that might cause anti-cancer, diabetes, and their complication. In this study, the effects and mechanisms of ZBHP on reversal of muscle atrophy were explored. C57BL/6 mice implanted with colon-26 adenocarcinoma were chosen to develop cancer cachexia for evaluating the effects of ZBHP on reversal of muscle atrophy. The body weight, survival time, inflammatory cytokines, and pathological changes of muscle were monitored. In addition, IGF-1/Akt and autophagy pathway members were analyzed to interpret the mechanism of drug response. The function and morphology of skeletal muscle in cachexia model were significantly disturbed, and the survival time was shortened. Consistently, inflammatory cytokines and muscle atrophy-related atrogin-1, MuRF1, and FOXO3 were significantly increased, and IGF-1/Akt and autophagy signal pathways were depressed. Treatment with ZBHP significantly alleviated tumor-free body weight reduction and cachexia-induced changes in cytokines and prolonged survival. ZBHP treatment not only inhibited the muscle atrophy-related genes but also activated the IGF-1/Akt and autophagy signal pathways to facilitate the protein synthesis. The results revealed that ZBHP treatment could inhibit the muscle atrophy induced by cancer cachexia and prolong the survival time, and ZBHP may be of value as a pharmacological alternative in treatment of cancer cachexia.

[Hemostatic and analgesic effect of Gonghuan Zhixue Tablet on mice].

PubMed

Fu, Ling-Mei; You, Zhao-Ling; Lei, Lei; Wen, Le-Xi; Chen, Huan-Ming

2004-03-01

To explore the hemostatic and analgesic effect of Gonghuan Zhixue Tablet (GHZXT) on mice and to produce experimental evidence for exploiting new drug for endometrorrhagia caused by Cu-intrauterine contraceptive device (Cu-IUD). Compared with 6-aminocaproic acid and notoginseng, the effects of GHZXT on clotting and bleeding time of mice with capillary method and severed tail were investigated; and compared with aspirin, the analgesic effects of GHZXT on mice were investigated with hot plate and torsive body method. The clotting time of mice was remarkably shortened with a rising of the dosage of GHZXT and the difference between each therapeutic group and distilled water group was remarkable. As compared with distilled water group, the bleeding time of each dosage group of GHZXT was obviously shortened; and each dosage of GHZXT could prolong the time of pain reaction to hot plate and decrease the degree of torsive body of the mice. Pharmacological experiment has proved that GHZXT has evident hemostatic and analgesic function.

Sedentary patterns, physical activity and health-related physical fitness in youth: a cross-sectional study.

PubMed

Júdice, Pedro B; Silva, Analiza M; Berria, Juliane; Petroski, Edio L; Ekelund, Ulf; Sardinha, Luís B

2017-03-04

Strong evidence indicates that moderate-vigorous physical activity (MVPA) is positively associated with fitness in youth, independent of total sedentary-time. Sedentary-time appears negatively associated with fitness only when it replaces MVPA. However, whether different sedentary-patterns affect health-related fitness is unknown. The associations between MVPA and sedentary-patterns with physical fitness were examined in 2698 youths (1262 boys) aged 13.4 ± 2.28 years. Sedentary-time (counts · minute -1  < 100) and PA were objectively measured by accelerometry. Each break (≥100 counts · min -1  < 2295) in sedentary-time and the frequency of daily bouts in non-prolonged (<30 min) and prolonged (≥30 min) sedentary-time were determined. The FITNESSGRAM® test battery was used to assess fitness. A standardized fitness composite-score (z-score) was calculated by summing the individual z-scores of the five tests adjusted to age and sex. Positive associations between MVPA and fitness were observed in both boys (β = 0.013, 95% CI: 0.005; 0.021) and girls (β = 0.014, 95% CI: 0.006; 0.022), independent of sedentary-patterns. Modest associations were found for the breaks in sedentary-time with fitness (β = 0.026, 95% CI: 0.009; 0.042), independent of total sedentary-time and MVPA in boys. In girls, non-prolonged sedentary bouts were positively associated with fitness (β = 0.014, 95% CI: 0.003; 0.024), independent of total sedentary-time and MVPA. These results reinforce that, independent of the time and patterns of sedentary behavior, MVPA is consistently associated with fitness in youth. Modest and inconsistent associations were found for sedentary behaviors. Breaking-up sedentary-time in boys and non-prolonged sedentary bouts in girls were positively associated with fitness, independent of total sedentary-time and MVPA. In order to enhance youth's fitness, public health recommendations should primarily target MVPA, still, suggestion to reduce and break-up sedentary-time may also be considered.

Choice reaction time to visual motion during prolonged rotary motion in airline pilots

NASA Technical Reports Server (NTRS)

Stewart, J. D.; Clark, B.

1975-01-01

Thirteen airline pilots were studied to determine the effect of preceding rotary accelerations on the choice reaction time to the horizontal acceleration of a vertical line on a cathode-ray tube. On each trial, one of three levels of rotary and visual acceleration was presented with the rotary stimulus preceding the visual by one of seven periods. The two accelerations were always equal and were presented in the same or opposite directions. The reaction time was found to increase with increases in the time the rotary acceleration preceded the visual acceleration, and to decrease with increased levels of visual and rotary acceleration. The reaction time was found to be shorter when the accelerations were in the same direction than when they were in opposite directions. These results suggest that these findings are a special case of a general effect that the authors have termed 'gyrovisual modulation'.

Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine.

PubMed

Kaube, H; Herzog, J; Käufer, T; Dichgans, M; Diener, H C

2000-07-12

Migraine aura is probably caused by cortical-spreading depression. No treatment for acute and severe migraine aura has been described previously. The effect of ketamine (25 mg intranasally) was studied in 11 patients with severe, disabling auras resulting from familial hemiplegic migraine. In five patients ketamine reproducibly reduced the severity and duration of the neurologic deficits, whereas in the remaining six patients no beneficial effect was seen. Ketamine offers, for the first time, a possible treatment option for severe and prolonged aura.

Evaluation and prediction of long term space environmental effects on non-metallic materials

NASA Technical Reports Server (NTRS)

Shepic, J. A.

1980-01-01

The effects of prolonged spacecraft materials were determined and the results compared with predicted behavior. The adhesion and dielectric properties of poly-thermaleze and therm-amid magnet wire insulation were studied. The tensile properties of Lexan, polyurethane, polyethelyne, lucite, and nylon were studied well as the flexure and tensile characteristic of Adlock 851, a phenolic laminate. The volume resistivity of Cho-seal, a conductive elastomer was also a examined. Tables show the time exposed at thermal vacuum, and the high, low, and average MPA and KSI.

Nanomedicine in GI

PubMed Central

Laroui, Hamed; Wilson, David S.; Dalmasso, Guillaume; Salaita, Khalid; Murthy, Niren; Sitaraman, Shanthi V.

2011-01-01

Recent advances in nanotechnology offer new hope for disease detection, prevention, and treatment. Nanomedicine is a rapidly evolving field wherein targeted therapeutic approaches using nanotechnology based on the pathophysiology of gastrointestinal diseases are being developed. Nanoparticle vectors capable of delivering drugs specifically and exclusively to regions of the gastrointestinal tract affected by disease for a prolonged period of time are likely to significantly reduce the side effects of existing otherwise effective treatments. This review aims at integrating various applications of the most recently developed nanomaterials that have tremendous potential for the detection and treatment of gastrointestinal diseases. PMID:21148398

In situ forming implants for the delivery of metronidazole to periodontal pockets: formulation and drug release studies.

PubMed

Kilicarslan, Muge; Koerber, Martin; Bodmeier, Roland

2014-05-01

This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.

Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release.

PubMed

Yuan, Peng; Southon, Peter D; Liu, Zongwen; Kepert, Cameron J

2012-09-21

The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release.

Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line.

PubMed

Freiburghaus, C; Janicke, B; Lindmark-Månsson, H; Oredsson, S M; Paulsson, M A

2009-06-01

Food components modify the risk of cancer at a large number of sites but the mechanism of action is unknown. In the present investigation, we studied the effect of the peptide lactoferricin derived from bovine milk lactoferrin on human colon cancer CaCo-2 cells. The cells were either untreated or treated with 2.0, 0.2, or 0.02 microM lactoferricin. Cell cycle kinetics were investigated with a bromodeoxyuridine DNA flow cytometric method. The results show that lactoferricin treatment slightly but significantly prolonged the S phase of the cell cycle. Lactoferricin treatment lowered the level of cyclin E1, a protein involved in the regulation of genes required for G(1)/S transition and consequently for efficient S phase progression. The slight prolongation of the S phase resulted in a reduction of cell proliferation, which became more apparent after a long treatment time.

Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation.

PubMed

Tennankore, Karthik K; Kim, S Joseph; Alwayn, Ian P J; Kiberd, Bryce A

2016-03-01

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Comparison of the Local Tolerability to 5 Long-acting Drug Nanosuspensions with Different Stabilizing Excipients, Following a Single Intramuscular Administration in the Rat.

PubMed

Chamanza, Ronnie; Darville, Nicolas; van Heerden, Marjolein; De Jonghe, Sandra

2018-01-01

To investigate the effects of common nanosuspension-stabilizing excipients on the nature and temporal evolution of histopathological changes at intramuscular (i.m.) administration sites, 5 groups of 39 male rats per group received a single injection of 1 of the 5 analogous crystalline drug nanosuspensions containing 200 mg/ml of an antiviral compound with particle sizes of ±200 nm and identical vehicle compositions, except for the type of nanosuspension stabilizer. The investigated stabilizers were poloxamer 338, poloxamer 407, d-α-tocopherol polyethylene glycol 1,000-succinate (TPGS), polysorbate 80, and polysorbate 80 combined with egg phosphatidylglycerol. Histopathology and immunohistochemistry revealed progressive inflammatory changes at the i.m. administration sites and the draining lymph nodes that differed according to the time point of sacrifice and the type of stabilizer. Although the overall time course of inflammatory changes was similar across the groups, differences in the nature, severity, and timing of the inflammatory response were observed between animals injected with poloxamer- or TPGS-containing nanosuspensions and those injected with formulations containing polysorbate 80. A more severe and prolonged active inflammatory phase, the presence of multinucleate giant cells, prolonged macrophage infiltration of the formulation depot, and more persistent histiocytic infiltrates in the lymph nodes were observed in the polysorbate 80-containing nanosuspension groups. Such vehicle-mediated effects could influence the overall tolerability profile of long-acting nanosuspensions.

Cathepsin G-Dependent Modulation of Platelet Thrombus Formation In Vivo by Blood Neutrophils

PubMed Central

Faraday, Nauder; Schunke, Kathryn; Saleem, Sofiyan; Fu, Juan; Wang, Bing; Zhang, Jian; Morrell, Craig; Dore, Sylvain

2013-01-01

Neutrophils are consistently associated with arterial thrombotic morbidity in human clinical studies but the causal basis for this association is unclear. We tested the hypothesis that neutrophils modulate platelet activation and thrombus formation in vivo in a cathepsin G-dependent manner. Neutrophils enhanced aggregation of human platelets in vitro in dose-dependent fashion and this effect was diminished by pharmacologic inhibition of cathepsin G activity and knockdown of cathepsin G expression. Tail bleeding time in the mouse was prolonged by a cathepsin G inhibitor and in cathepsin G knockout mice, and formation of neutrophil-platelet conjugates in blood that was shed from transected tails was reduced in the absence of cathepsin G. Bleeding time was highly correlated with blood neutrophil count in wildtype but not cathepsin G deficient mice. In the presence of elevated blood neutrophil counts, the anti-thrombotic effect of cathepsin G inhibition was greater than that of aspirin and additive to it when administered in combination. Both pharmacologic inhibition of cathepsin G and its congenital absence prolonged the time for platelet thrombus to form in ferric chloride-injured mouse mesenteric arterioles. In a vaso-occlusive model of ischemic stroke, inhibition of cathepsin G and its congenital absence improved cerebral blood flow, reduced histologic brain injury, and improved neurobehavioral outcome. These experiments demonstrate that neutrophil cathepsin G is a physiologic modulator of platelet thrombus formation in vivo and has potential as a target for novel anti-thrombotic therapies. PMID:23940756

Effects of simulated weightlessness on regional blood flow specifically during cardiovascular stress

NASA Technical Reports Server (NTRS)

Harrison, D. C.

1986-01-01

Significant changes in the cardiovasular system of humans and animals have been observed following exposure to prolonged periods of weightlessness during space flight. Although adaption to weightlessness is relatively uncomplicated, marked changes in cardiovascular deconditioning become evident upon return to normal gravity, including orthostatic hypotension and tachycardia. Some evidence that myocardial degeneration occurs has been demonstrated in animals who have been immobilized for two months. Also, evidence of possible loss of myocardial mass following manned space flight has been obtained by means of echocardiographic studies. These findings have serious implications in light of the increasing frequency and duration of Space Shuttle missions and the prospect of extended space station missions in the future. A number of both military and civilian investigators, including middle-aged scientists, will probably encounter prolonged periods of weightlessness. It has been imperative, therefore, to determine the effects of prolonged weightlessness on cardiovascular deconditioning and whether such effects are cumulative or reversible. The research project conducted under NASA Cooperative Agreement NCC 2-126 was undertaken to determine the effects of prolonged simulated weightlessness on regional blood flow. Research results are reported in the three appended publications.

The effects of prolonged running on foot posture: a repeated measures study of half marathon runners using the foot posture index and navicular height

PubMed Central

2013-01-01

Background Different foot postures are associated with alterations in foot function, kinetics and the subsequent occurrence of injury. Little is known about changes in foot posture following prolonged weightbearing exercise. This study aimed to identify changes in foot posture after running a half marathon. Methods Foot posture was measured using the Foot Posture Index (FPI-6) and navicular height in thirty volunteer participants before and after running a half marathon. FPI-6 scores were converted to Rasch logit values and means compared for these and navicular height using an ANOVA. Results There was a 5 mm drop in navicular height in both feet when measured after the half marathon (P < 0.05). The FPI-6 showed a side x time interaction with an increase in score indicating a more ‘pronated’ position in the left foot of + 2 [Rasch value + 1.7] but no change in the right foot (+ 0.4 [+ 0.76]) following the half marathon. Conclusion The apparent differences between the FPI-6 and navicular height on the right foot may be because the FPI-6 takes soft tissue contour changes into consideration whilst the navicular height focuses on skeletal changes. The changes in foot posture towards a more pronated position may have implications for foot function, and therefore risk of injury; shoe fit and comfort and also the effect of therapeutic orthoses worn during prolonged running. PMID:23705863

The Effect of Optokinetic Stimulation on Perceptual and Postural Symptoms in Visual Vestibular Mismatch Patients.

PubMed

Van Ombergen, Angelique; Lubeck, Astrid J; Van Rompaey, Vincent; Maes, Leen K; Stins, John F; Van de Heyning, Paul H; Wuyts, Floris L; Bos, Jelte E

2016-01-01

Vestibular patients occasionally report aggravation or triggering of their symptoms by visual stimuli, which is called visual vestibular mismatch (VVM). These patients therefore experience discomfort, disorientation, dizziness and postural unsteadiness. Firstly, we aimed to get a better insight in the underlying mechanism of VVM by examining perceptual and postural symptoms. Secondly, we wanted to investigate whether roll-motion is a necessary trait to evoke these symptoms or whether a complex but stationary visual pattern equally provokes them. Nine VVM patients and healthy matched control group were examined by exposing both groups to a stationary stimulus as well as an optokinetic stimulus rotating around the naso-occipital axis for a prolonged period of time. Subjective visual vertical (SVV) measurements, posturography and relevant questionnaires were assessed. No significant differences between both groups were found for SVV measurements. Patients always swayed more and reported more symptoms than healthy controls. Prolonged exposure to roll-motion caused in patients and controls an increase in postural sway and symptoms. However, only VVM patients reported significantly more symptoms after prolonged exposure to the optokinetic stimulus compared to scores after exposure to a stationary stimulus. VVM patients differ from healthy controls in postural and subjective symptoms and motion is a crucial factor in provoking these symptoms. A possible explanation could be a central visual-vestibular integration deficit, which has implications for diagnostics and clinical rehabilitation purposes. Future research should focus on the underlying central mechanism of VVM and the effectiveness of optokinetic stimulation in resolving it.

Comparable Effects of High-Intensity Interval Training and Prolonged Continuous Exercise Training on Abdominal Visceral Fat Reduction in Obese Young Women.

PubMed

Zhang, Haifeng; Tong, Tom K; Qiu, Weifeng; Zhang, Xu; Zhou, Shi; Liu, Yang; He, Yuxiu

2017-01-01

This study compared the effect of prolonged moderate-intensity continuous training (MICT) on reducing abdominal visceral fat in obese young women with that of work-equivalent (300 kJ/training session) high-intensity interval training (HIIT). Forty-three participants received either HIIT ( n = 15), MICT ( n = 15), or no training (CON, n = 13) for 12 weeks. The abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) of the participants were measured through computed tomography scans preintervention and postintervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Following HIIT and MICT, comparable reductions in AVFA (-9.1, -9.2 cm 2 ), ASFA (-35, -28.3 cm 2 ), and combined AVFA and ASFA (-44.7, -37.5 cm 2 , p > 0.05) were observed. Similarly, reductions in fat percentage (-2.5%, -2.4%), total fat mass (-2.8, -2.8 kg), and fat mass of the android (-0.3, -0.3 kg), gynoid (-0.5, -0.7 kg), and trunk (-1.6, -1.2 kg, p > 0.05) regions did not differ between HIIT and MICT. No variable changed in CON. In conclusion, MICT consisting of prolonged sessions has no quantitative advantage, compared with that resulting from HIIT, in abdominal visceral fat reduction. HIIT appears to be the predominant strategy for controlling obesity because of its time efficiency.

DELETERIOUS EFFECTS OF HIGH FAT DIETS ON SURVIVAL TIME OF X-IRRADIATED MICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ershoff, B.H.

1961-02-01

The effects of multiple sublethal doses of total body x-irradiation were determined on survival time of male mice fed either a purified fat-free ration or a similar diet supplemented with 2, 10, 20, or 30% cottonseed oil, marganine fat, or butter fat. The effects obtnined were dependent on the amount and source of dietary fat. At levels of 2 or 10% of the diet, cottonseed oil and margarine fat increased survival time over that on the fat-free ration. When these fats were fed at higher levels (i.e., 20 or 30% of the diet), however, survival time was decreased below thatmore » obtained at the lower levels of supplementation. In contrast to the results obtained with the cottonseed oil or margarine fat supplements, butter fat at levels of 2 or 10% of the diet did not prolong survival over that on the fat-free ration; nor did it decrease survival time when fed at higher levels in the diet. (auth)« less

Impact of acute versus prolonged exercise and dehydration on kidney function and injury.

PubMed

Bongers, Coen C W G; Alsady, Mohammad; Nijenhuis, Tom; Tulp, Anouk D M; Eijsvogels, Thijs M H; Deen, Peter M T; Hopman, Maria T E

2018-06-01

Exercise and dehydration may be associated with a compromised kidney function and potential signs of kidney injury. However, the kidney responses to exercise of different durations and hypohydration levels are not yet known. Therefore, we aimed to compare the effects of acute versus prolonged exercise and dehydration on estimated glomerular filtration rate (eGFR) and kidney injury biomarkers in healthy male adults. A total of 35 subjects (23 ± 3 years) were included and invited for two study visits. Visit 1 consisted of a maximal cycling test. On Visit 2, subjects performed a submaximal exercise test at 80% of maximal heart rate until 3% hypohydration. Blood and urine samples were taken at baseline, after 30 min of exercise (acute effects; low level of hypohydration) and after 150 min of exercise or when 3% hypohydration was achieved (prolonged effects, high level of hypohydration). Urinary outcome parameters were corrected for urinary cystatin C, creatinine, and osmolality. Subjects dehydrated on average 0.6 ± 0.3% and 2.9 ± 0.7% after acute and prolonged exercise, respectively (P < 0.001). The eGFR cystatin C did not differ between baseline and acute exercise (118 ± 11 vs. 116 ± 12 mL/min/1.73 m 2 , P = 0.12), whereas eGFR cystatin C was significantly lower after prolonged exercise (103 ± 16 mL/min/1.73 m 2 , P < 0.001). We found no difference in osmolality corrected uKIM1 concentrations after acute and prolonged exercise (P > 0.05), and elevated osmolality corrected uNGAL concentrations after acute and prolonged exercise (all P-values < 0.05). In conclusion, acute exercise did barely impact on eGFR cystatin C and kidney injury biomarkers, whereas prolonged exercise is associated with a decline in eGFR cystatin C and increased biomarkers for kidney injury. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Work capability during isolation.

PubMed

Gushin, V I; Efimov, V A; Smirnova, T M

1996-01-01

The aim of this study was to investigate the effects of prolonged isolation on the higher psychic functions, like working memory, attention concentration, and intellect (problem solving and decision making), and on sensory-motor skills and stress resistance. Previous Soviet simulation studies and the ISEMSI isolation experiment have indicated that prolonged isolation can affect higher psychic functions. A set of psychological tests in the form of a computer game was presented each workday to the chamber crew and to the ground crew serving as a control group. In analyzing the data it was taken into account that performance can be affected not only by the influence of isolation, but also by a learning process and by subject motivation. In addition, a distinction was made between absolute score and stability (range) of the score. Analysis of the chamber crew's work capability as a function of time showed the occurrence of three distinct periods of adaptation: (1) a period of acute adaptation in week 1, (2) a period of stable adaptation during weeks 3-6, and (3) a period of "final effort" in weeks 8-9. While in general the effect of isolation on the absolute scores was minor, larger ranges for the scores in "working memory," "attention concentration," and "calculation under time deficit" tests are an indication of increased instability, probably due to stress resistance. The 4 female subjects of the combined groups scored significantly higher than the 5 males in "attention concentration/distribution," "spatial orientation," "intuition in visual search," and "logical decision making under time deficit." Males presented higher scores in "calculation under time deficit" and working memory, and higher stability in "attention concentration" and "calculation under time deficit."

Ventricular dysfunction in type 1 myotonic dystrophy: electrical, mechanical, or both?

PubMed

Lindqvist, P; Mörner, S; Olofsson, B O; Backman, C; Lundblad, D; Forsberg, H; Henein, M Y

2010-09-03

Myotonic dystrophy type 1 (DM1) is a systemic disease which affects the heart and may be a cause of sudden death. Conduction disturbances are the major cardiac abnormalities seen in this condition. We sought to assess electrical and mechanical cardiac functions to identify abnormalities that might explain sudden cardiac death in DM1. Thirty six patients with DM1 and 16 controls were studied using echocardiography including myocardial Doppler. ECG recordings were also obtained. Left ventricular (LV) dimensions were maintained but systolic function was reduced (p<0.001), including stroke volume (p<0.05). LV segmental myocardial isovolumic contraction time was prolonged (p<0.001) and correlated with PR interval (p<0.001). Isovolumic relaxation time was prolonged (p<0.05) and filling time was reduced (p<0.001). LV cavity was significantly asynchronous demonstrated by prolonged total isovolumic time (t-IVT) (p<0.001), high Tei index (p<0.001) and low ejection index (p<0.001). Right ventricular (RV) strain was reduced (p<0.001) as were its systolic and diastolic velocities (p<0.05 for both). 22/36 patients had prolonged LV t-IVT>12.3 s/min (upper 95% normal CI), 13 of whom had PR≥200 ms, 11 had QRS duration>120 ms (5 had combined abnormality) and the remaining 5 had neither. Over the 3 years follow up 10 patients had events, 6 of them cardiac. t-IVT was prolonged in 5/6 patients, PR interval in 4 and QRS duration in one. In DM1 patients, LV conventional measurements are modestly impaired but cardiac time relations suggest marked asynchronous cavity function. Although our findings were primarily explained on the basis of long PR interval or broad QRS duration a minority presented an evidence for myocardial cause of asynchrony rather than electrical. Early identification of such abnormalities may guide towards a need for additional electrical resynchronization therapy which may improve survival in a way similar to what has been shown in heart failure trials. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Dexmedetomidine as an adjuvant to 0.5% ropivacaine in ultrasound-guided axillary brachial plexus block.

PubMed

Koraki, E; Stachtari, C; Kapsokalyvas, I; Stergiouda, Z; Katsanevaki, A; Trikoupi, A

2018-06-01

The aim of this study was to elucidate the effect of dexmedetomidine added to ropivacaine on the onset and duration of sensory and motor block and duration of analgesia of ultrasound-guided axillary brachial plexus block. Thirty-seven ASA physical status I-II patients with elective forearm and hand surgery under ultrasound-guided axillary brachial plexus block were randomly divided into 2 groups. Patients in ropivacaine-dexmedetomidine group (group RD, n = 19) received 15 mL of 0.5% ropivacaine with 100 μg (1 mL) dexmedetomidine, and patients in ropivacaine group (group R, n = 18) received 15 mL of 0.5% ropivacaine with 1 mL of normal saline. Onset time and duration of sensory and motor block and duration of analgesia were assessed. Duration of sensory block (U-value = 35, P < .001), duration of motor block (P = .001) and duration of analgesia (P < .001) were extended in group RD compared to group R. Onset time of sensory block in group RD was significantly faster than in group R (U-value = 65.5, P = .001). Onset time of motor block showed no significant difference between the 2 groups (U-value = 116.5, P = .096). Adverse reactions were reported only in group RD (bradycardia in 2 and hypotension in 3 patients). Our study indicated that dexmedetomidine 100 μg as adjuvant on ultrasound-guided axillary plexus block significantly prolonged the duration of sensory block and analgesia, as well as accelerated the time to onset of sensory block. These results should be weighed against the increased risks of motor block prolongation, transient bradycardia and hypotension and allow for attentive optimism, only if prolonged clinical trials provide a definitive answer. © 2017 John Wiley & Sons Ltd.

A study of ventricular contractility and other parameters possibly related to vasodepressor syncope

NASA Technical Reports Server (NTRS)

Hyatt, K. H.; Sullivan, R. W.; Spears, W. R.; Vetter, W. R.

1973-01-01

The effects of diminished orthostatic and exercise tolerance resulting from prolonged bedrest were studied by noninvasion methods to determine if alterations in myocardial contractility were induced by bedrest. These methods were apexcardiography, systolic time intervals, and echocardiography. It is concluded that bedrest causes detrimental alterations in the contractile state of the myocardium which accounts for the decreases in maximal oxygen uptaken during exercise after bedrest. Tabulated test data are included.

Halogen effect for improving high temperature oxidation resistance of Ti-50Al by anodization

NASA Astrophysics Data System (ADS)

Mo, Min-Hua; Wu, Lian-Kui; Cao, Hua-Zhen; Lin, Jun-Pin; Zheng, Guo-Qu

2017-06-01

The high temperature oxidation resistance of Ti-50Al was significantly improved via halogen effect which was achieved by anodizing in an ethylene glycol solution containing with fluorine ion. The anodized Ti-50Al with holes and micro-cracks could be self-repaired during oxidation at 1000 °C. The thickness of the oxide scale increases with the prolonging of oxidation time. On the basis of halogen effect for improving the high temperature oxidation resistance of Ti-50Al by anodization, only fluorine addition into the electrolyte can effectively improve the high temperature oxidation resistance of Ti-50Al.

Emotional attentional control predicts changes in diurnal cortisol secretion following exposure to a prolonged psychosocial stressor.

PubMed

Lenaert, Bert; Barry, Tom J; Schruers, Koen; Vervliet, Bram; Hermans, Dirk

2016-01-01

Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been associated with several psychological disorders. Hence, the identification of individual difference variables that predict variations in HPA-axis activity represents an important challenge for psychiatric research. We investigated whether self-reported attentional control in emotionally demanding situations prospectively predicted changes in diurnal salivary cortisol secretion following exposure to a prolonged psychosocial stressor. Low ability to voluntarily control attention has previously been associated with anxiety and depressive symptomatology. Attentional control was assessed using the Emotional Attentional Control Scale. In students who were preparing for academic examination, salivary cortisol was assessed before (time 1) and after (time 2) examination. Results showed that lower levels of self-reported emotional attentional control at time 1 (N=90) predicted higher absolute diurnal cortisol secretion and a slower decline in cortisol throughout the day at time 2 (N=71). Difficulty controlling attention during emotional experiences may lead to chronic HPA-axis hyperactivity after prolonged exposure to stress. These results indicate that screening for individual differences may foster prediction of HPA-axis disturbances, paving the way for targeted disorder prevention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fresh Osteochondral Allograft Transplantation: Is Graft Storage Time Associated With Clinical Outcomes and Graft Survivorship?

PubMed

Schmidt, Kenneth J; Tírico, Luís E; McCauley, Julie C; Bugbee, William D

2017-08-01

Regulatory concerns and the popularity of fresh osteochondral allograft (OCA) transplantation have led to a need for prolonged viable storage of osteochondral grafts. Tissue culture media allow a longer storage time but lead to chondrocyte death within the tissue. The long-term clinical consequence of prolonged storage is unknown. Patients transplanted with OCAs with a shorter storage time would have lower failure rates and better clinical outcomes than those transplanted with OCAs with prolonged storage. Cohort study; Level of evidence, 3. A matched-pair study was performed of 75 patients who received early release grafts (mean storage, 6.3 days [range, 1-14 days]) between 1997 and 2002, matched 1:1 by age, diagnosis, and graft size, with 75 patients who received late release grafts (mean storage time, 20.0 days [range, 16-28 days]) from 2002 to 2008. The mean age was 33.5 years, and the median graft size was 6.3 cm 2 . All patients had a minimum 2-year follow-up. Evaluations included pain, satisfaction, function, failures, and reoperations. Outcome measures included the modified Merle d'Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) form, and Knee Society function (KS-F) scale. Clinical failure was defined as revision OCA transplantation or conversion to arthroplasty. Among patients with grafts remaining in situ, the mean follow-up was 11.9 years (range, 2.0-16.8 years) and 7.8 years (range, 2.3-11.1 years) for the early and late release groups, respectively. OCA failure occurred in 25.3% (19/75) of patients in the early release group and 12.0% (9/75) of patients in the late release group ( P = .036). The median time to failure was 3.5 years (range, 1.7-13.8 years) and 2.7 years (range, 0.3-11.1 years) for the early and late release groups, respectively. The 5-year survivorship of OCAs was 85% for the early release group and 90% for the late release group ( P = .321). No differences in postoperative pain and function were noted between the groups. Ninety-one percent of the early release group and 93% of the late release group reported satisfaction with OCA results. The transplantation of OCA tissue with prolonged storage is safe and effective for large osteochondral lesions of the knee and has similar clinical outcomes and satisfaction to the transplantation of early release grafts.

Prevalence of QT interval prolongation in patients admitted to cardiac care units and frequency of subsequent administration of QT interval-prolonging drugs: a prospective, observational study in a large urban academic medical center in the US.

PubMed

Tisdale, James E; Wroblewski, Heather A; Overholser, Brian R; Kingery, Joanna R; Trujillo, Tate N; Kovacs, Richard J

2012-06-01

Cardiac arrest due to torsades de pointes (TdP) is a rare but catastrophic event in hospitals. Patients admitted to cardiac units are at higher risk of drug-induced QT interval prolongation and TdP, due to a preponderance of risk factors. Few data exist regarding the prevalence of QT interval prolongation in patients admitted to cardiac units or the frequency of administering QT interval-prolonging drugs to patients presenting with QT interval prolongation. The aim of this study was to determine the prevalence of Bazett's-corrected QT (QT(c)) interval prolongation upon admission to cardiac units and the proportion of patients presenting with QT(c) interval prolongation who are subsequently administered QT interval-prolonging drugs during hospitalization. This was a prospective, observational study conducted over a 1-year period (October 2008-October 2009) in 1159 consecutive patients admitted to two cardiac units in a large urban academic medical centre located in Indianapolis, IN, USA. Patients were enrolled into the study at the time of admission to the hospital and were followed daily during hospitalization. Exclusion criteria were age <18 years, ECG rhythm of complete ventricular pacing, and patient designation as 'outpatient' in a bed and/or duration of stay <24 hours. Data collected included demographic information, past medical history, daily progress notes, medication administration records, laboratory data, ECGs, telemetry monitoring strips and diagnostic reports. All patients underwent continuous cardiac telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of admission. QT intervals were determined manually from lead II of 12-lead ECGs or from continuous lead II telemetry monitoring strips. QT(c) interval prolongation was defined as ≥470 ms for males and ≥480 ms for females. In both males and females, QT(c) interval >500 ms was considered abnormally high. A medication was classified as QT interval-prolonging if there were published data indicating that the drug causes QT interval prolongation and/or TdP. Study endpoints were (i) prevalence of QT(c) interval prolongation upon admission to the Cardiac Medical Critical Care Unit (CMCCU) or an Advanced Heart Care Unit (AHCU); (ii) proportion of patients admitted to the CMCCU/AHCU with QT(c) interval prolongation who subsequently were administered QT interval-prolonging drugs during hospitalization; (iii) the proportion of these higher-risk patients in whom TdP risk factor monitoring was performed; (iv) proportion of patients with QT(c) interval prolongation who subsequently received QT-prolonging drugs and who experienced further QT(c) interval prolongation. Of 1159 patients enrolled, 259 patients met exclusion criteria, resulting in a final sample size of 900 patients. mean (± SD) age, 65 ± 15 years; female, 47%; Caucasian, 70%. Admitting diagnoses: heart failure (22%), myocardial infarction (16%), atrial fibrillation (9%), sudden cardiac arrest (3%). QT(c) interval prolongation was present in 27.9% of patients on admission; 18.2% had QT(c) interval >500 ms. Of 251 patients admitted with QT(c) interval prolongation, 87 (34.7%) were subsequently administered QT interval-prolonging drugs. Of 166 patients admitted with QT(c) interval >500 ms, 70 (42.2%) were subsequently administered QT interval-prolonging drugs; additional QT(c) interval prolongation ≥60 ms occurred in 57.1% of these patients. QT(c) interval prolongation is common among patients admitted to cardiac units. QT interval-prolonging drugs are commonly prescribed to patients presenting with QT(c) interval prolongation.

Setting the scene: definition of prolonged seizures, acute repetitive seizures, and status epilepticus. Do we know why seizures stop?

PubMed

Cross, J Helen

2014-10-01

Status epilepticus is recognised as an acute emergency requiring urgent intervention. The optimal timing of such an intervention during a prolonged seizure, and the reasons for such, have provided much discussion. For operational purposes, a definition of a prolonged seizure of ≥5 minutes requiring intervention appears justified. However, a definition of status epilepticus of ≥30 minutes should stand, with the proportion of seizures proceeding to this clinical state remaining small. The reasons for this may be inherent to an individual, but an understanding of the mechanisms underlying the predisposition may lead to improved management pathways in the future.

[Causation between occupational prolonged standing time during progestation and pregnancy related complications].

PubMed

Weng, Ting-ting; Xu, Ye-qing; Yan, Shuang-qin; Pan, Wei-jun; Tao, Fang-biao

2013-06-01

To describe the epidemiological characteristics of profession related long-standing behavior during preconception and progestation, and to probe the relationship between prolonged standing jobs and the common pregnancy related complications among pregnant women, in Ma' anshan city,Anhui province. In this cohort study, subjects who had their first antenatal examination at Ma' anshan Maternal and Child Care Centers were recruited under informed consent, from October 2008 to October 2010. All the information were collected through questionnaires in the first, second and third trimesters respectively. Three questionnaires were filled in by subjects under the guidance of healthcare takers. In the study, the 75(th) percentile of prolonged-standing times were 4.0 h/d and 3.0 h/d respectively in preconception and progestation. The characteristics of pregnant women with low social/economic status, prone to be involved in stand-long occupation. Results in logistic regression analysis, prolonged-standing jobs during preconception was the risk factor of pregnancy-induced hypertension and severe anemia. The adjusted odds ratios were 2.05 (95%CI:1.26-3.31) and 1.38(95%CI:1.03-1.85)respectively. Prolonged standing jobs appeared to be common occupational exposure to and risks of both pregnant woman and their fetus. Exposure to these kinds of jobs during preconception could increase the risk of pregnancy-induced hypertension and severe anemia. In order to promote maternal health programs, all the related occupational risk factors should be valued and avoided during preconception and pregnancy.

Prolonged length of stay in hospitalized internal medicine patients.

PubMed

Barba, Raquel; Marco, Javier; Canora, Jesús; Plaza, Susana; Juncos, Sara Nistal; Hinojosa, Juan; Bailon, Manuel Mendez; Zapatero, Antonio

2015-12-01

Targeting patients with prolonged hospitalizations may represent an effective strategy for reducing average hospital length of stay (LOS). We sought to characterize predictors of prolonged hospitalization among internal medicine patients in an effort to guide future improvement efforts. We conducted a retrospective cohort study using administrative data of internal medicine patients from all hospitals of the Spanish Public Health Service between January 1st, 2005 and December 31st, 2013. Multivariable logistic regression was performed to assess the association between sociodemographic and clinical variables and prolonged LOS, defined as >30days. Of 5,275,139 discharges, 166,470 (3.2%) had a prolonged LOS. Prolonged hospitalizations accounted for 17.4% of total inpatient days and contributed 0.5days to an average LOS of 9.8days during the study period. Prolonged hospitalizations were associated with younger age (odds ratio [OR]: 0.97 per 10-year increase in age, 95% confidence interval [CI]: 0.96-0.98) and male gender (OR 0.88 IC95% 0.87-0.89). Compared to patients without prolonged LOS, prolonged LOS patients were more likely to require a palliative care consult (OR: 2.48, 95% CI: 2.39-2.58), surgery (OR: 6.9 95% CI: 6.8-7.0); and be discharged to a post-acute-care facility (OR: 2.91, 95% CI: 2.86-2.95). Prolonged hospitalizations in a small proportion of patients were an important contributor to overall LOS and particularly affected complex hospital stays who were not discharged home. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Predicting QT prolongation in humans during early drug development using hERG inhibition and an anaesthetized guinea-pig model

PubMed Central

Yao, X; Anderson, D L; Ross, S A; Lang, D G; Desai, B Z; Cooper, D C; Wheelan, P; McIntyre, M S; Bergquist, M L; MacKenzie, K I; Becherer, J D; Hashim, M A

2008-01-01

Background and purpose: Drug-induced prolongation of the QT interval can lead to torsade de pointes, a life-threatening ventricular arrhythmia. Finding appropriate assays from among the plethora of options available to predict reliably this serious adverse effect in humans remains a challenging issue for the discovery and development of drugs. The purpose of the present study was to develop and verify a reliable and relatively simple approach for assessing, during preclinical development, the propensity of drugs to prolong the QT interval in humans. Experimental approach: Sixteen marketed drugs from various pharmacological classes with a known incidence—or lack thereof—of QT prolongation in humans were examined in hERG (human ether a-go-go-related gene) patch-clamp assay and an anaesthetized guinea-pig assay for QT prolongation using specific protocols. Drug concentrations in perfusates from hERG assays and plasma samples from guinea-pigs were determined using liquid chromatography-mass spectrometry. Key results: Various pharmacological agents that inhibit hERG currents prolong the QT interval in anaesthetized guinea-pigs in a manner similar to that seen in humans and at comparable drug exposures. Several compounds not associated with QT prolongation in humans failed to prolong the QT interval in this model. Conclusions and implications: Analysis of hERG inhibitory potency in conjunction with drug exposures and QT interval measurements in anaesthetized guinea-pigs can reliably predict, during preclinical drug development, the risk of human QT prolongation. A strategy is proposed for mitigating the risk of QT prolongation of new chemical entities during early lead optimization. PMID:18587422

Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes.

PubMed

Vinogradova, I A; Bukalev, A V; Zabezhinski, M A; Semenchenko, A V; Khavinson, V Kh; Anisimov, V N

2007-12-01

The effects of Ala-Glu-Asp-Gly peptide (Epithalon) on the life span and development of spontaneous tumors were studied in female rats exposed to standard, natural for North-Western Russia, and constant illumination. The mean life span of animals exposed to constant or natural illumination decreased by 13.5 and 25.5%, the maximum by 9 and 7 months, respectively, and spontaneous tumors developed much more rapidly than in animals living under conditions of the standard light regimen. Epithalon (0.1 microg daily 5 times a week from the age of 4 months) did not change the life span of rats living under conditions of standard day/night regimen, while in rats exposed to the natural and constant light it promoted prolongation of the maximum life span by 95 and 24 days, respectively. Epithalon prolonged the mean life span of the last 10% of rats exposed to natural and constant illumination, treated with Epithalon, by 137 and 43 days, respectively. This peptide exhibited virtually no effect on the development of spontaneous tumors in rats exposed to standard and constant illumination, but significantly inhibited their development in rats exposed to natural light.

Prolonged effect of the stratospheric pathway in linking Barents-Kara Sea sea ice variability to the midlatitude circulation in a simplified model

NASA Astrophysics Data System (ADS)

Zhang, Pengfei; Wu, Yutian; Smith, Karen L.

2018-01-01

To better understand the dynamical mechanism that accounts for the observed lead-lag correlation between the early winter Barents-Kara Sea (BKS) sea ice variability and the later winter midlatitude circulation response, a series of experiments are conducted using a simplified atmospheric general circulation model with a prescribed idealized near-surface heating over the BKS. A prolonged effect is found in the idealized experiments following the near-surface heating and can be explicitly attributed to the stratospheric pathway and the long time scale in the stratosphere. The analysis of the Eliassen-Palm flux shows that, as a result of the imposed heating and linear constructive interference, anomalous upward propagating planetary-scale waves are excited and weaken the stratospheric polar vortex. This stratospheric response persists for approximately 1-2 months accompanied by downward migration to the troposphere and the surface. This downward migration largely amplifies and extends the low-level jet deceleration in the midlatitudes and cold air advection over central Asia. The idealized model experiments also suggest that the BKS region is the most effective in affecting the midlatitude circulation than other regions over the Arctic.

The persisting effect of unemployment on health and social well-being in men early in working life.

PubMed

Wadsworth, M E; Montgomery, S M; Bartley, M J

1999-05-01

In our studies of the effects of unemployment in the early working life of men in a British national birth cohort we have shown elsewhere that this experience was part of a longer term accumulation of social and health disadvantage. This present study asks whether men's unemployment also inflicted potential longterm damage to future socio-economic chances and health. We therefore constructed indicators of socio-economic circumstances and health at 33 years from factors already shown to be associated with health in later life. For the socio-economic indicator we used a combination of income, occupational status and home ownership and described this as socio-economic capital. For the health indicator we combined scores of body mass index, leisure time exercise, frequency of eating fresh fruit and of smoking, and described this as health capital. After controlling for pre-labour market socio-economic and health factors, prolonged unemployment is shown here to reduce significantly both socio-economic and health capital by age 33 years. We conclude that the experience of prolonged unemployment early in the working life of this population of young men looks likely to have a persisting effect on their future health and socio-economic circumstances.

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial.

PubMed

Malamiri, Reza Azizi; Ghaempanah, Mahdieh; Khosroshahi, Nahid; Nikkhah, Ali; Bavarian, Behrouz; Ashrafi, Mahmoud Reza

2012-09-01

Status epilepticus and acute prolonged seizures are the most commonly occurring neurological emergencies in children. Such events have high morbidity and mortality rates along with poor long-term outcomes, depending on their duration and causes. Therefore, such seizures warrant urgent treatment using appropriate doses of anticonvulsants. Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures. Sixty children (30 in each group) with convulsive status epilepticus and acute prolonged seizures were enrolled and randomly assigned to receive either valproate or phenobarbital. The main outcome variable was termination of all convulsive activity within 20 min of starting anticonvulsant infusion. Intravenous rapid loading of valproate was successful in seizure termination in (27/30, 90%) of patients compared to phenobarbital (23/30, 77%) (p = 0.189). Clinically significant adverse effects occurred in 74% patients of the phenobarbital group and 24% patients of the valproate group (p < 0.001). In conclusion, rapid loading of valproate is effective and safe in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children. Intravenous valproate should be considered as a suitable choice for terminating status epilepticus and acute prolonged seizures in children. Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.