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Joy in the Journey!

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Austin Foster
Austin Foster

Life By M. Piper

If then you have been raised with Christ, seek the things that are above, where Christ is, seated at the right hand of God. Set your mind on things that are above, not on things that are on earth. For you have died, and your life is hidden with Christ in God. When Christ who is your life appears, then you also will appear with him in glory.

Life by M. Piper

In 2019, Piper wrote, starred in and made her directorial debut with the "anti-romcom" Rare Beasts,[44] before appearing alongside Sally Hawkins, Alice Lowe, and David Thewlis in Eternal Beauty, directed by Craig Roberts.[45] The following year, in August 2020, Piper co-created and starred in the critically acclaimed Sky Atlantic series I Hate Suzie. The series was also co-created and written by Secret Diary of a Call Girl creator Lucy Prebble. Piper portrays the titular Suzie Pickles, a former child screen star whose life and career are turned upside down by a compromising phone hack. Critics noted her own experience of having been a prodigious young singer-turned-actress who becomes famous at a young age will no doubt have informed her new role as Pickles. The Guardian gave it a five-star review, describing Piper's character as "nude, lewd and joyously off the rails" in "this scabrously funny drama".[46] In March 2021, it was announced that Piper would appear in the film adaptation of a children's book called Catherine Called Birdy.[47]

Background: Due to multiple and interacting factors, Latino children are disproportionately at risk for overweight and obesity in the United States. Childhood obesity increases the risk for adverse physical and psychosocial outcomes throughout the lifespan. Intensive behavioral interventions recommended in primary care settings may not conform to current practices, and the most vulnerable populations are often unable to access these services. Community Health Workers (CHWs) offer a promising approach to bridging the gap between vulnerable communities and culturally competent services. La Vida Buena (The Good Life) is an 8-week family-focused intervention for Latino children 5-8 years old and their parents or caregivers who are patients at a Federally-Qualified Community Health Center (FQHC). It is a culturally and linguistically appropriate curriculum, facilitated by CHWs, that targets family behaviors to foster a healthy lifestyle in order to prevent and mitigate childhood overweight and obesity.

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Although most behavioural research in the past was done with rodent models, zebrafish are an upcoming animal model due to their prolific breeding, which results in a large number of offspring for experimental purposes in a relatively short duration (34). Other advantages of zebrafish as compared to rodents in terms of an animal model are their longer lifespan and robust phenotypes, as they display apparent and easily quantifiable behavioural endpoints (35). The variety of behavioural and molecular tools available for use with zebrafish makes them outstanding models for helping to investigate neuromolecular mechanisms. Zebrafish can provide a comparatively quick indication of possible functional efficacy. In addition, this diurnal vertebrate has several fundamental similarities to humans (36). All these characteristics make zebrafish a better animal model for behavioural research. Due to their cost effectiveness, reliability and scalability, this study opted for zebrafish as an animal model over rodents. In the context of this experiment, zebrafish are also emerging as a promising model organism for experimental studies of sleep and its related disorders as its pineal gland and retina contains circadian oscillators that drive the rhythms for synthesizing melatonin (37) and regulating sleep in a similar fashion as in humans (38).

Effect of early life DEX treatment on the locomotion parameters, brain melatonin levels and nfkb mRNA expression level of adult zebrafish. (A) Effect of early life DEX treatment (2 and 20 mg/l) in adult zebrafish; total distance travelled, (B) % time spent in the upper zone of tank, (C) level of brain melatonin and (D) nfkb mRNA expression level. The data were analyzed by one way ANOVA followed by dunnett post-hoc test, and was represented as the mean SEM, n=8. *P

Effect of melatonin and PB on zebrafish sleep-like behaviour. Effect of melatonin (10 mg/kg; positive control) and PB (10 and 30 mg/Kg) on early life DEX treated (2 and 20 mg/ml) adult zebrafish on sleep-like behaviour, which is characterized by (A) total distance travelled, (B) % time spent in the upper zone of the tank (place preference) and (C) inactive duration (quiescent phase). The data were analyzed by one way ANOVA followed by dunnett post-hoc test, and was represented as the mean SEM, n=8. *P

Effect of PB on sleep-related genes in early life DEX treated adult zebrafish. Effect of PB (10 and 30 mg/kg) on early life DEX treated (2 and 20 mg/ml) adult zebrafish on sleep related gene; (A) aanat1 mRNA expression level, (B) aanat2 mRNA expression level, (C) MT1 mRNA expression level, (D) MT2 mRNA expression level and (E) stress related gene nfkb mRNA expression level. The data were analyzed by one way ANOVA followed by dunnett post-hoc test, and was represented as the mean SEM, n=8. **P

In addition to this, our data shows increased zebrafish locomotor activity and decreased time spent in the upper zone of the tank, which is characteristic of anxiety like behaviour as seen in previous zebrafish studies (4). Some other studies have also demonstrated that the DEX can disrupt the glucocorticoid receptor signaling pathway and alter the neuroendocrine system, which impacts behaviour such as hyper activity in adulthood (3,23), that can interfere with sleep behaviour. Furthermore, nfkb mRNA expression is significantly higher in DEX treated fish in comparison to normal fish, which suggests that early life stress has an impact on the expression of stress-activated proteins, which can further influence normal sleep regulation as sleep is a resting state with anti-oxidative properties (48).

Nowadays, sleep disorders are becoming a general societal problem in all age groups of people. Studies suggest that sleep problems have a negative impact on health and cognitive performance (49). Stress is the most powerful contributor to poor sleep and exposure to stress during childhood has been suggested to be a crucial factor for the development of sleep disorders in adulthood (5). Currently, many substances are available for the treatment of sleep disorders, but they have some sort of side effects such as daytime sleepiness (50). The interest of researchers in medicinal plants as a natural source of many active components has noticeably increased in the past 20 years as drugs against various pharmacological targets are developed. Nowadays, natural products are in great demand due to their prevalent biological properties and for the discovery of many types of effective bioactive compounds in natural products (33). In the present study, PB has enhanced sleep like behaviour (decrease in total distance travelled, increased time spent in the upper zone and in a quiescent state), which is similar to melatonin treated group which we have used as a positive control in the study. Additionally, PB was found to significantly suppress nfkb mRNA expression in early life stressed fish, similar to that seen in the melatonin treated group. This suggets that PB has similar anti-oxidative properties and potentially it can help to reduce oxidative stress induced by early life stress.

Moreover, it is well established that the effect of melatonin on sleep is mediated by melatonin receptors (9). In the present study, PB significantly increased the MT2 mRNA expression in the DEX treated fish, which is similar to melatonin treated group which we have used as a positive control. Increased expression of MT2 mRNA suggests that it facilitates the expression of melatonin to maintain an optimum level throughout the dark h to expedite physiological activities. Pandi-Perumal et al (53) has suggested that melatonin exerts its physiological actions by interacting with melatonin receptors. On the other hand, there was no significant change in MT1 mRNA expression. Further investigations are necessary to examine whether MT1 exhibits different expression patterns in the zebrafish brain which might explain the discrepancies observed between both types of receptors. Alternatively, the results could be explained by the high level of exogenous melatonin in the positive control group. This would trigger the same negative feedback mechanisms that result in a reduced level of annat2 and hence melatonin production as previously discussed. In addition, melatonin undergoes biexponential decay in blood plasma, with a first distribution half-life of 2 min and a second metabolic half-life of 20 min due to melatonin catabolism by the liver (54). It is possible that these correction mechanisms results in an overshoot, causing melatonin levels to fall below their normal concentration at ZT16 when the zebrafish were removed for gene expression analysis, four h after treatment. As the level of melatonin falls below normal, MT2 expression is upregulated to compensate for this, but not MT1 as melatonin has a higher affinity for MT1 as compared to MT2 (55). The PB extract at a dose of 30 mg/kg also shows a similar effect on the melatonin related genes, lending credence to the idea that it can be used to improve sleep disruption as a result of a deficiency in melatonin. 041b061a72


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