26 research outputs found

    MODELING SLEEP AND WAKE BOUTS IN DROSOPHILA MELANOGASTER

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    Adequate sleep restores vital processes required for health and well-being; but the function and regulation of sleep is not well understood. Unfortunately, a definition of adequate sleep is unclear. On an hours-long timescale, consolidated and cycling sleep results in better health and performance outcomes. At shorter timescales, older studies report conflicting results regarding the relationship between sleep and wake bout durations. One approach to this problem has been to simply analyze the distribution of bout durations. While informative, this method eliminates the time relationship between bouts, which may be important. Here, we develop a model that describes the relationship between sleep and wake bout durations using the model organism, Drosophila melanogaster, which exhibits behavioral and molecular homology to human sleep. We present an exploratory analysis of the data to gain a better understanding of the sleep bout duration distribution by considering a broader range of potential distributions than considered in previous studies. We use the results of the distribution analysis to develop a model for sleep bout durations in the fly based upon their past sleep and wake history and find that this relationship should not be ignored

    Glioma-derived exosomes drive the differentiation of neural stem cells to astrocytes

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    Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, colony stimulating factor and interleukin 6 of the STAT3 family and Hes family bHLH transcription factor 1 also increased by 2.3, 10, 4.7 and 2.9 fold, respectively. We further examined the effects of these exosomes on rat fetal neural stem cell (rNSC) differentiation using the secreted exosomes from U87 glioma cells or exosomes from U87 cells that were stimulated with interleukin 1β (IL-1β). The rNSCs, extracted from rat brains at embryonic day 14 (E14), underwent a culture protocol that normally leads to predominant (∼90%) differentiation to ODCs. However, in the presence of the exosomes from untreated or IL-1β-treated U87 cells, significantly more cells differentiated into astrocytes, especially in the presence of exosomes obtained from the IL-1β-challenged glioma cells. Moreover, glioma-derived exosomes appeared to inhibit rNSC differentiation into ODCs or astrocytes as indicated by a significantly increased population of unlabeled cells. A portion of the resulting astrocytes coexpressed both CD133 and glial fibrillary acidic protein (GFAP) suggesting that exosomes from U87 cells could promote astrocytic differentiation of NSCs with features expected from a transformed cell. Our data clearly demonstrated that exosomes secreted by human glioma cells provide a strong driving force for rat neural stem cells to differentiate into astrocytes, uncovering potential pathways and therapeutic targets that might control this aggressive tumor type

    Formulation and evaluation of orally disintegrating clopidogrel tablets

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    ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs) that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC). DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability

    African American Mothers Talk to Their Preadolescents About Honesty and Lying

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    Objectives: While existing work points to the ways parenting behaviors and specific value socialization approaches influence children's internalization of moral values (Baumrind, Child Development 43, 261-267, 1972; Hoffman, Empathy and moral development: Implications for caring and justice, 2001; Grusec & Davidov, Child Development, 81, 687-709, 2010), little work has considered the experiences of African American and lower-income families. The current study capitalized on the availability of 53 video-recorded mother-preadolescent conversations about their disagreements from the Early Head Start Research and Evaluation Project (Vogel et al., Early head start children in grade 5: Long-term follow-up of the early head start research and evaluation study sample. OPRE Report # 2011-8, 2010). Methods: Using inductive analysis, we assessed mothers' affective tone, communication styles, and message content during the discussion of problems involving honesty and lying. Results: Mothers tended to display warm yet firm affect, incorporate both autonomy-supportive and dominant-directive communication styles, assert that lying is never acceptable, and explain why lying is problematic. Conclusions: Mothers' affect, communication styles, and message content reflected a no-nonsense approach to transmitting values about honesty to their children. To our knowledge, the current study is the first qualitative observational investigation of low-income African American mothers' conversations regarding honesty with their children. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

    COVID-19 Presenting as Acute Limb Ischaemia

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    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that developed in late 2019 and early 2020 has caused thousands of deaths and has had an enormous impact on our health systems and economies. Coronavirus disease 2019 (COVID-19) complications include disseminated coagulation and thrombosis, but, to the best of our knowledge, the literature to date on these manifestations has been limited. Herein, we report an unusual presentation in a 43-year-old man with a medical history of diabetes and hypertension who presented with dyspnoea and acute pain in his right leg and was found to have acute limb ischaemia and diabetic ketoacidosis. Our case adds to the literature regarding arterial thrombosis in COVID-19

    Modeling Sleep and Wake Bouts in Drosophila Melanogaster

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    Adequate sleep restores vital processes required for health and well-being; but the function and regulation of sleep is not well understood. Unfortunately, a definition of adequate sleep is unclear. On an hours-long timescale, consolidated and cycling sleep results in better health and performance outcomes. At shorter timescales, older studies report conflicting results regarding the relationship between sleep and wake bout durations. One approach to this problem has been to simply analyze the distribution of bout durations. While informative, this method eliminates the time relationship between bouts, which may be important. Here, we develop a model that describes the relationship between sleep and wake bout durations using the model organism, Drosophila melanogaster, which exhibits behavioral and molecular homology to human sleep. We present an exploratory analysis of the data to gain a better understanding of the sleep bout duration distribution by considering a broader range of potential distributions than considered in previous studies. We use the results of the distribution analysis to develop a model for sleep bout durations in the fly based upon their past sleep and wake history and find that this relationship should not be ignored

    Sibling Influences on Adolescent Alcohol Use During the Spring 2020 COVID-19 Pandemic Shutdown

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    Objective: To examine the bidirectional associations between adolescent siblings\u27 alcohol use before and during the onset of the COVID-19 pandemic in Spring 2020 and whether youths\u27 stress about missed social connections (i.e., social disruption stress) moderated these associations. Method: The sample consisted of 682 families (2,046 participants) with two adolescent siblings (older siblings: Mage = 15.67 years, 51% female; younger siblings: Mage = 13.14 years, 48% female) and one parent (Mage = 45.15 years; 85% female) from five Midwestern U.S. states. Siblings reported on their own drinking and social disruption stress before and during the onset of the pandemic via online surveys. Results: Accounting for younger siblings\u27 earlier drinking and other confounders, older siblings\u27 prepandemic drinking predicted a greater likelihood of younger siblings\u27 drinking during the Spring 2020 pandemic shutdown. This assocation was not moderated by younger siblings\u27 social disruption stress. The association between younger siblings\u27 prepandemic drinking and older siblings\u27 drinking during the shutdown was moderated by older siblings\u27 social disruption stress. Specifically, younger siblings\u27 earlier drinking was more strongly related to older siblings\u27 drinking during the shutdown if older siblings reported more social disruption stress. Conclusions: Siblings are important socialization agents of alcohol use during adolescence. Sibling interventions may be particularly salient during times of stress and isolation when youths\u27 social interactions with peers may be limited

    Associations Between Older Siblings\u27 Substance Use and Younger Siblings\u27 Substance Use Intentions: Indirect Effects Via Substance Use Expectations

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    Objective We examined the direct and indirect effects of older siblings\u27 substance use behaviors (I.e., cannabis and e-cigarettes) on younger siblings\u27 later substance use intentions via their substance use expectations. Material and methods Data were collected from 682 families (N=2,046) with two adolescent siblings (older siblings: M age = 15.67 years, 51% female; younger siblings: M age = 13.14years, 48% female) and one parent (M age = 45.15 yeras; 85% female). Participants completed annual online surveys at two occasions. Older siblings reported on their cannabis and e-cigarette use frequencies (Time 1) and younger siblings reported on their substance use expectations (Time 1) and Intentions (Time 1 and 2); parents reported on adolescents\u27 sociodemographic characteristics and their own substance use (Time 2). Results Structural equation modeling results suggested that older siblings\u27 cannabis and e-cigarette use was indirectly related to younger siblings\u27 later intentions to use these substances through their positive expectations about substances, after accounting for younger siblings\u27 earlier intentions to use substances and control variables including parents\u27 and friends\u27 use. There were no significant direct relations between older siblings\u27 cannabis or e-cigarette use and younger siblings\u27 intentions to use them. Conclusions Findings indicate that older siblings are critical and unique socialization agents of younger siblings\u27 expectations and intentions to use substances. Intervention and prevention programs that target adolescents\u27 substance use should consider the ways in which siblings shape each other\u27s substance use
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