scholarly journals The importance of individual variation for the interpretation of behavioural studies: ethanol effects vary with basal activity level in zebrafish larvae

Author(s):  
Raissa Davis ◽  
Floris Luchtenburg ◽  
Michael Richardson ◽  
Marcel Schaaf ◽  
Christian Tudorache ◽  
...  

AbstractStandardization and reduction of variation is key to behavioural screening of animal models in toxicological and pharmacological studies. However, individual variation in behavioural and physiological phenotypes remains in each laboratory population and can undermine the understanding of toxicological and pharmaceutical effects and their underlying mechanisms. Here, we used zebrafish (ABTL-strain) larvae to explore individual consistency in activity level and emergence time, across subsequent days of early development (6–8 dpf). We also explored the correlation between these two behavioural parameters. We found inter-individual consistency over time in activity level and emergence time, but we did not find a consistent correlation between these parameters. Subsequently, we investigated the impact of variation in activity level on the effect of a 1% ethanol treatment, suitable for our proof-of-concept case study about whether impact from pharmacological treatments might be affected by inter-individual variation in basal locomotion. The inter-individual consistency over time in activity level did not persist in this test. This was due to the velocity change from before to after exposure, which turned out to be a dynamic individual trait related to basal activity level: low-activity individuals raised their swimming velocity, while high-activity individuals slowed down, yielding diametrically opposite response patterns to ethanol exposure. We therefore argue that inter-individual consistency in basal activity level, already from 6 dpf, is an important factor to take into account and provides a practical measure to improve the power of statistical analyses and the scope for data interpretation from behavioural screening studies.

2020 ◽  
Author(s):  
Caroline Vrana-Diaz ◽  
Priya Balasubramanian ◽  
Nathalie Kayadjanian ◽  
Jessica Bohonowych ◽  
Theresa V. Strong

Abstract Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder in which hyperphagia (excessive appetite) is a hallmark feature. Understanding how weight changes over time in this population is important for capturing the contemporary natural history of the disorder as well as assessing the impact of new treatments for hyperphagia. Therefore, we aimed to determine the feasibility of a remote assessment of weight change over time in PWS. Methods: We developed a text message-based, prospective cohort study of adolescents and adults with PWS to assess changes in weight and body mass index (BMI) over a six-month period. Weight was collected weekly, while changes in height, living situation, access to food, activity level, and medication were collected at three-month intervals. Results: One hundred and sixty-five participants enrolled in the study, with a mean age of 19.7 years (range 12 - 48). There was considerable variability in weight across participants (range: 76.8 – 207.7 kg). Thirty-three percent of the participants were normal weight, while 15% were overweight and 52% were obese. Overall, the weight of the study participants increased over the study period (mean weight change +2.35%), while BMI was relatively stable, albeit high (mean BMI of 31.4 at baseline, mean BMI percent change + 1.42%). Changes in living situation, activity, food access, and medication had limited impact on weight and BMI changes. Multivariable analysis found that time, sex, age, and percentage of life on growth hormone (GH) therapy were statistically significant fixed effects. Participants submitted more than 95% of possible weight data points across the 26 weeks of the study. Conclusions: This remote, observational study of weight change in PWS showed small increases in weight and BMI over a six-month period. Participants were highly compliant with this text message-based study, suggesting that mobile technology-based data collection was manageable for the participants. We anticipate that the results of this study will inform clinical trials for hyperphagia/obesity related therapies in PWS and provide a basis for understanding the efficacy of new therapies for hyperphagia in the real-world setting.


2020 ◽  
Author(s):  
Caroline Vrana-Diaz ◽  
Priya Balasubramanian ◽  
Nathalie Kayadjanian ◽  
Jessica Bohonowych ◽  
Theresa V. Strong

Abstract Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder in which hyperphagia (excessive appetite) is a hallmark feature. Understanding how weight changes over time in this population is important for capturing the contemporary natural history of the disorder as well as assessing the impact of new treatments for hyperphagia.Methods: We developed a text message-based, prospective cohort study of adolescents and adults with PWS to assess changes in weight and body mass index (BMI) over a six-month period. Weight was collected weekly, while changes in height, living situation, access to food, activity level, and medication were collected at three-month intervals.Results: One hundred and sixty-five participants enrolled in the study, with a mean age of 19.7 years (range 12 - 48). There was considerable variability in weight across participants (range: 76.8 – 207.7 kg). Thirty-three percent of the participants were normal weight, while 15% were overweight and 52% were obese. Overall, the weight of the study participants increased over the study period (mean weight change +2.35%), while BMI was relatively stable, albeit high (mean BMI of 31.4 at baseline, mean BMI percent change + 1.42%). Changes in living situation, activity, food access, and medication had limited impact on weight and BMI changes. Multivariable analysis found that time, sex, age, and percentage of life on growth hormone (GH) therapy were statistically significant fixed effects.Conclusions: This remote, observational study of weight change in PWS showed small increases in weight and BMI over a six-month period. Participants were highly compliant with this text message-based study, suggesting that mobile technology-based data collection was manageable for the participants. We anticipate that the results of this study will inform clinical trials for hyperphagia/obesity related therapies in PWS and provide a basis for understanding the efficacy of new therapies for hyperphagia in the real-world setting.


Behaviour ◽  
2016 ◽  
Vol 153 (13-14) ◽  
pp. 1745-1762 ◽  
Author(s):  
Bawan Amin ◽  
Hans Slabbekoorn ◽  
Marcel Schaaf ◽  
Christian Tudorache

Individual animals show consistent differences in behavioural responses when coping with environmental challenges. Consistency over time and across context in a behavioural trait is an indication for animal personality. Chronotypes refer to consistent inter-individual differences in diurnal rhythmicity driven by underlying variation in circadian clock processes. Personality traits and chronotype may relate to a single behavioural syndrome, but few studies have investigated such a link explicitly. Here, we explored zebrafish larvae for the presence of consistency in activity levels and timing, and their correlation with and without external cues (Zeitgeber: light–dark cycle versus constant light). We found individual consistency in activity level and timing, and their correlation independent of the presence of Zeitgeber: early-active individuals were less active overall than late-active individuals. Our study suggests a link between personality and chronotype and provides new insights into the early development of individual variation in behavioural tendencies of zebrafish.


Author(s):  
Rafael Orbolato ◽  
Rômulo Araújo Fernandes ◽  
Bruna Camilo Turi ◽  
Monique Yndawe Castanho-Araujo ◽  
Carolina Rodrigues Bortolatto ◽  
...  

Given the importance of physical activity for health promotion and for the prevention of chronic non-communicable diseases, the Unified Health System (SUS) has changed its strategy of action in the last decades, trying to adopt preventive activities, seeking better quality of life of the Brazilian population and reduce costs with treatment of diseases. The aim of this study was to investigate changes in physical activity and sedentary behavior patterns in users of the Brazilian National Unified Health System during 18 months and the impact of sex and time on such variables. One hundred and ninety-eight participants (58 men and 140 women) were evaluated. Physical activity level was assessed using the Baecke questionnaire. Men had higher scores in all physical activity variables compared to women: walking (p-value = 0.013), cycling (p-value = 0.001) and commuting (p-value= 0.007), but not for TV watching (p-value = 0.362). After 18 months, in the overall sample, walking score increased 25.9% (95%CI = 10.6 to 41.1), but not cycling (1.5% [95%CI = -2.7 to 5.7]), commuting (14.4% [95%CI = -0.4 to 29.3]) and TV watching (1.6% [95%CI = -5.7 to 9.1]). Men were usually more active than women in active behaviors, but not in TV watching. However, differences over time were similar between sexes.


Crisis ◽  
2011 ◽  
Vol 32 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Friedrich Martin Wurst ◽  
Isabella Kunz ◽  
Gregory Skipper ◽  
Manfred Wolfersdorf ◽  
Karl H. Beine ◽  
...  

Background: A substantial proportion of therapists experience the loss of a patient to suicide at some point during their professional life. Aims: To assess (1) the impact of a patient’s suicide on therapists distress and well-being over time, (2) which factors contribute to the reaction, and (3) which subgroup might need special interventions in the aftermath of suicide. Methods: A 63-item questionnaire was sent to all 185 Psychiatric Clinics at General Hospitals in Germany. The emotional reaction of therapists to patient’s suicide was measured immediately, after 2 weeks, and after 6 months. Results: Three out of ten therapists suffer from severe distress after a patients’ suicide. The item “overall distress” immediately after the suicide predicts emotional reactions and changes in behavior. The emotional responses immediately after the suicide explained 43.5% of the variance of total distress in a regression analysis. Limitations: The retrospective nature of the study is its primary limitation. Conclusions: Our data suggest that identifying the severely distressed subgroup could be done using a visual analog scale for overall distress. As a consequence, more specific and intensified help could be provided to these professionals.


1986 ◽  
Vol 56 (03) ◽  
pp. 371-375 ◽  
Author(s):  
Peretz Weiss ◽  
Hillel Halkin ◽  
Shlomo Almog

SummaryWithin-individual variation over time in the clearance (Cl) and effect (PT%) of warfarin, was measured in 25 inpatients (group I) studied after standard single or individualized split loading doses and 1-3 times (n = 16) 8-16 weeks later during maintenance. Mean Cl (2.5 α 0.9 ml/min) was similar in both phases but significant changes occurred in 6/16 patients, exceeding those expected from within-individual variation alone (defined by its 95% tolerance limits -24% to +62%). Initial PT% (21 α 5) was unaffected by dosing schedule, total or free plasma warfarin, varying between patients by only 18-24%. Mean initial and maintenance dose-PT% ratios (8.2 mg/d: 21% and 4.1 mg/d: 40%) were similar but significant changes in sensitivity to warfarin occurred in 4/16 patients. In group I and 64 other outpatients on maintenance therapy, between-individual variability was 36-52% for Cl and 49-56% for effect. PT% correlated best (r = 0.56) with free and total plasma warfarin but poorly with dose (r = 0.29), with only 30% of PT% variance explained at best, due to high between patient variability.Warfarin dose prediction whether based on extrapolation from initial effects to the maintenance phase, or on iterative methods not allowing for between- or within-patient variation in warfarin clearance or effect which may occur independently over time, have not improved on empirical therapy. This, due to the elements of biological variability as well as the intricacy of the warfarin - prothrombin complex interaction not captured by any kinetic-dynamic model used for prediction to date.


1997 ◽  
Vol 36 (4II) ◽  
pp. 947-957 ◽  
Author(s):  
Shahrukh Rafi Khan

This paper has a two-fold objective: first, to examine the terms on which Pakistan receives aid and whether its debt situation is sustainable, and second, to examine the impact of aid and debt on economic growth. It is found that there is little encouraging that can be said about how the terms on which Pakistan has received aid over time have changed, and its current debt situation is not sustainable. Also reported is the analysis done elsewhere which shows that aid has a negative (Granger) causal impact on GDP, and aid has a robust negative impact on economic growth after controlling for supplyside shocks. We provide various reasons for this negative association.


2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.


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