A cross-syndrome comparison of sleep-dependent learning on a cognitive procedural task

Sleep plays a key role in the consolidation of newly acquired information and skills into long term memory. Children with Down syndrome (DS) and Williams syndrome (WS) frequently experience sleep problems, abnormal sleep architecture and difficulties with learning; thus, we predicted that children from these clinical populations would demonstrate impairments in sleep-dependent memory consolidation relative to children with typical development (TD) on a cognitive procedural task: The Tower of Hanoi. Children with DS (n = 17), WS (n = 22) and TD (n = 34) completed the Tower of Hanoi task. They were trained on the task either in the morning or evening, then completed it again following counterbalanced retention intervals of daytime wake and night time sleep. Children with TD and with WS benefitted from sleep for enhanced memory consolidation and improved their performance on the task by reducing the number of moves taken to completion, and by making fewer rule violations. We did not find any large effects of sleep on learning in children with DS, suggesting that these children are not only delayed, but atypical in their learning strategies. Importantly, our findings have implications for educational strategies for all children, specifically considering circadian influences on new learning and the role of children’s night time sleep as an aid to learning.<br/

Exploring Military Veteran Students’ Pathways in Engineering Education

Military Veteran Students’ Pathways in Engineering Education (Year 1: Award# 1428646)Military veterans hold tremendous promise for expanding and diversifying the engineeringworkforce. Given the diverse backgrounds of veterans, their increasing numbers, and thegrowing national demand for engineering professionals, the timing is ideal to study theconditions under which student veterans pursue engineering education and the factors that offerthem the greatest support for success. Increasing the participation of veterans in engineeringoffers the possibility of enhancing engineering’s diversity in many needed dimensions since,compared to civilian students, veterans are more likely to be older, first-generation collegestudents, disabled, African American, or Latino. Yet, little is known regarding the educationalpathways and experiences of student veterans into engineering. This project therefore aims toaddress gaps in the literature on student veterans in engineering through a comparative casestudy across four institutions: University of San Diego, North Carolina State University, PurdueUniversity, and Clemson University. The following research questions are addressed:1. Why do veterans pursue a Bachelor’s degree in engineering?2. How do military experiences shape student veterans’ educational experiences?3. What are the experiences of student veterans in engineering education?4. How do institutions support veterans in engineering education?The research plan incorporates content analysis of academic policies that student veteransencounter, interviews with key informants on each campus, focus group interviews with studentveterans, and in-depth student interviews to elicit rich narratives. The theoretical frameworkbuilds on Tinto’s student integration model and Schlossberg’s adult transition theory. Data willbe analyzed with the lens of intersectionality to elucidate differences stemming from theintersection of military status with race, gender, ability, sexual orientation, and socioeconomicstatus. Findings will provide context and information for various applications, such as:development of new strategies to support student veterans\u27 success, identification of overlookedareas to promote student veterans\u27 participation in engineering, and generation of criticalinformation for development of larger-scale studies for investigating student veterans inengineering. Thus, this study has potential for broad systemic impact by diversifying pathways toand through engineering programs, and in capitalizing on the informal and real-worldexperiences of engineering student veterans

Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study

Abstract Background While the United States has the largest number of children with type 1 diabetes mellitus, less is known regarding adult-onset disease. The present study utilizes nationwide data to compare the incidence of type 1 diabetes in youth (0–19 years) to that of adults (20–64 years). Methods In this longitudinal study, the Clinformatics® Data Mart Database was used, which contains information from 61 million commercially insured Americans (years 2001–2015). Incidence rates and exact Poisson 95% confidence intervals were calculated by age group, sex, census division, and year of diagnosis. Changes in rates over time were assessed by negative binomial regression. Results Overall, there were 32,476 individuals who developed type 1 diabetes in the cohort. The incidence rate was greatest in youth aged 10–14 years (45.5 cases/100,000 person-years); however, because adulthood spans over a longer period than childhood, there was a greater number of new cases in adults than in youth (n = 19,174 adults; n = 13,302 youth). Predominance in males was evident by age 10 and persisted throughout adulthood. The male to female incidence rate ratio was 1.32 (95% CI 1.30–1.35). The incidence rate of type 1 diabetes in youth increased by 1.9% annually from 2001 to 2015 (95% CI 1.1–2.7%; P < 0.001), but there was variation across regions. The greatest increases were in the East South Central (3.8%/year; 95% CI 2.0–5.6%; P < 0.001) and Mountain divisions (3.1%/year; 95% CI 1.6–4.6%; P < 0.001). There were also increases in the East North Central (2.7%/year; P = 0.010), South Atlantic (2.4%/year; P < 0.001), and West North Central divisions (2.4%/year; P < 0.001). In adults, however, the incidence decreased from 2001 to 2015 (−1.3%/year; 95% CI −2.3% to −0.4%; P = 0.007). Greater percentages of cases were diagnosed in January, July, and August for both youth and adults. The number of new cases of type 1 diabetes (ages 0–64 years) in the United States is estimated at 64,000 annually (27,000 cases in youth and 37,000 cases in adults). Conclusions There are more new cases of type 1 diabetes occurring annually in the United States than previously recognized. The increase in incidence rates in youth, but not adults, suggests that the precipitating factors of youth-onset disease may differ from those of adult-onset disease.https://deepblue.lib.umich.edu/bitstream/2027.42/139053/1/12916_2017_Article_958.pd

Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to regulate inflammasome activation

BACKGROUND: Asbestos exposure is related to various diseases including asbestosis and malignant mesothelioma (MM). Among the pathogenic mechanisms proposed by which asbestos can cause diseases involving epithelial and mesothelial cells, the most widely accepted one is the generation of reactive oxygen species and/or depletion of antioxidants like glutathione. It has also been demonstrated that asbestos can induce inflammation, perhaps due to activation of inflammasomes. METHODS: The oxidation state of thioredoxin was analyzed by redox Western blot analysis and ROS generation was assessed spectrophotometrically as a read-out of solubilized formazan produced by the reduction of nitrotetrazolium blue (NTB) by superoxide. Quantitative real time PCR was used to assess changes in gene transcription. RESULTS: Here we demonstrate that crocidolite asbestos fibers oxidize the pool of the antioxidant, Thioredoxin-1 (Trx1), which results in release of Thioredoxin Interacting Protein (TXNIP) and subsequent activation of inflammasomes in human mesothelial cells. Exposure to crocidolite asbestos resulted in the depletion of reduced Trx1 in human peritoneal mesothelial (LP9/hTERT) cells. Pretreatment with the antioxidant dehydroascorbic acid (a reactive oxygen species (ROS) scavenger) reduced the level of crocidolite asbestos-induced Trx1 oxidation as well as the depletion of reduced Trx1. Increasing Trx1 expression levels using a Trx1 over-expression vector, reduced the extent of Trx1 oxidation and generation of ROS by crocidolite asbestos, and increased cell survival. In addition, knockdown of TXNIP expression by siRNA attenuated crocidolite asbestos-induced activation of the inflammasome. CONCLUSION: Our novel findings suggest that extensive Trx1 oxidation and TXNIP dissociation may be one of the mechanisms by which crocidolite asbestos activates the inflammasome and helps in development of MM

‘You can’t start a car when there’s no petrol left’: a qualitative study of patient, family and clinician perspectives on implantable cardioverter defibrillator deactivation

Objective: To explore the attitudes towards implantable cardioverter defibrillator (ICD) deactivation and initiation of deactivation discussions among patients, relatives and clinicians. Design: A multiphase qualitative study consisting of in situ hospital ICD clinic observations, and semistructured interviews of clinicians, patients and relatives. Data were analysed using a constant comparative approach. Setting: One tertiary and two district general hospitals in England. Participants: We completed 38 observations of hospital consultations prior to ICD implantation, and 80 interviews with patients, family members and clinicians between 2013 and 2015. Patients were recruited from preimplantation to postdeactivation. Clinicians included cardiologists, cardiac physiologists, heart failure nurses and palliative care professionals. Results: Four key themes were identified from the data: the current status of deactivation discussions; patients’ perceptions of deactivation; who should take responsibility for deactivation discussions and decisions; and timing of deactivation discussions. We found that although patients and doctors recognised the importance of advance care planning, including ICD deactivation at an early stage in the patient journey, this was often not reflected in practice. The most appropriate clinician to take the lead was thought to be dependent on the context, but could include any appropriately trained member of the healthcare team. It was suggested that deactivation should be raised preimplantation and regularly reviewed. Identification of trigger points postimplantation for deactivation discussions may help ensure that these are timely and inappropriate shocks are avoided. Conclusions: There is a need for early, ongoing and evolving discussion between ICD recipients and clinicians regarding the eventual need for ICD deactivation. The most appropriate clinician to instigate deactivation discussions is likely to vary between patients and models of care. Reminders at key trigger points, and routine discussion of deactivation at implantation and during advance care planning could prevent distressing experiences for both the patient and their family at the end of life

Association of the degree of adiposity and duration of obesity with measures of cardiac structure and function: The CARDIA study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109634/1/oby20865.pd

Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism

peer-reviewedAutism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+ Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.The APC Microbiome Institute is a research institute funded by Science Foundation Ireland (SFI) through the Irish Government's National Development Plan. J.F·C, T.G.D, C.S., S.A.J. and C.G.M.G. are supported by SFI (Grant Nos. SFI/12/RC/2273). S.A.J is also funded by SFI-EU 16/ERA-HDHL/3358. J.F·C, C.S. and T.G.D have research support from Mead Johnson, Cremo, 4D Pharma, Suntory Wellness, and Nutricia. J.F.C, C.S., T.G.D and G.C. have spoken at meetings sponsored by food and pharmaceutical companies