Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy

AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.     

Research Review: Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype

This review critically examines the research findings which characterize the cognitive, behavioral, and neuroanatomical features of Williams syndrome (WS). This article analyzes 178 published studies in the WS literature covering the following areas: 1) General intelligence, 2) Language skills, 3) Visuospatial and face processing skills, 4) Behavior patterns and hypersociability, 5) Musical abilities, and 6) Brain structure and function. We identify methodological issues relating to small sample size, use and type of control groups, and multiple measures of task performance. Previously described 'peaks' within the cognitive profile are closely examined to assess their veracity. This review highlights the need for methodologically sound studies that utilize multiple comparison groups, developmental trajectories, and longitudinal analyses to examine the WS phenotype, as well as those that link brain structure and function to the cognitive and behavioral phenotype of WS individuals.     

A Survey of the Nature and Perceived Impact of Quality Improvement Activities in Pain Management

We surveyed members of the American Pain Society (APS) to determine if they were engaged in quality assurance or improvement (QA/I) activities. If so, we queried them about the characteristics of these activities and their perceptions of whether their data appear to show improvements, decrements, or no change in pain outcomes. Of the 222 respondents from at least 180 institutions, 201 (91%) reported that their institutions had a continuous improvement program. One hundred forty-three respondents reported having data on at least one of six pain outcomes at two points in time. The majority reported that their data revealed improvements in outcomes. A large number, however, had not collected data on important outcomes, such as pain intensity and patient functioning. Many APS members are collecting longitudinal data, and interpreting the data as revealing improvements in outcomes. There is a need for rigorously controlled assessment of the effects of QA/I programs on pain outcomes.     

Using motor milestones as a multistep process to screen preterm infants for cerebral palsy

Pediatricians often informally use motor milestones to screen infant motor development, and one advantage is that they can be used during sequential office visits, as a multistep screening process. In this study we evaluated six motor milestones (roll prone to supine, roll supine to prone, sit with support, sit without support, crawl and cruise) as a multi-step process in screening for cerebral palsy in 173 high-risk preterm infants (<33 weeks gestational age) who had been followed with sequential developmental assessments for at least 18 months. At the 18 to 24 month evaluation, 31 (18%) had cerebral palsy. We found that using the motor milestones as serial screening tests for cerebral palsy was more effective in terms of positive predictive value than any individual milestone alone. Limited community resources can be more efficiently used if preterm infants with delays in more than four motor milestones are referred for further evaluation and early intervention services.     

Are resident work-hour limitations beneficial to the trauma profession?

In July 2003, work-hour restrictions were implemented by the Accreditation Council for Graduate Medical Education (ACGME) to limit resident duty hours. Attending surgeon work-hours have not been similarly reduced, and many trauma services have added emergency general surgery responsibilities. We hypothesized that trauma attending/resident work-hour disparity may disincentivize residents from selecting trauma careers and that trauma directors would view ACGME regulations negatively. We conducted a 6-month study of resident and in-house trauma attending self-reported hours at a level I trauma center and sent a questionnaire to 172 national level I trauma directors (TDs) regarding work-hours restrictions. TD survey response rate was 48 per cent; 100 per cent of 15 residents and 6 trauma faculty completed work-hour logs. Attending mean hours (87.1/ wk), monthly calls (5), and shifts > 30 hours exceeded that of all resident groups. Case volume was similar. Residents viewed their lifestyle more favorably than the lifestyle of the trauma attending (Likert score 3.6 +/- 0.5 vs Likert score 2.5 +/- 0.8, P = 0.0003). Seventy-one per cent cited attending work hours and lifestyle as a reason not to pursue a trauma career. Nationally, 80 per cent of trauma surgeons cover emergency general surgery; 40 per cent work greater than 80 hours weekly, compared with < 1 per cent of surgical trainees (P < 0.0001). Most TDs feel that residents do not spend more time reading (89%) or operating (96%); 68 per cent feel patient care has suffered as a result of duty-hours restrictions. Seventy-one per cent feel residents will not select trauma surgery as a career as a result of changes in duty hours. Perceived trauma attending/ resident work-hour disparity may disincentive trainees from trauma career selection. TDs view resident duty-hour restrictions negatively.     

Brief Report: Evaluating the Effectiveness of Music to Obtain More Accurate Blood Pressure Readings in Children with Williams Syndrome

Journal of Autism and Developmental Disorders - This study examined if listening to music will improve the accuracy of blood pressure (BP) readings in children with Williams syndrome (WS)....     

Cancer Awareness Resources to go (C.A.R.T.): A project to increase access to cancer patient education at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Background. Being told one has cancer requires patients to understand their disease and cope with physical and emotional aspects of their illness. Methods. The Cancer Awareness Resources to go (C.A.R.T.) Planning Committee identified the need to provide cancer patients expanded access to educational materials. Results. For those patients who find it helpful to use booklets and medical pamphlets as an information source, having resources readily available on a mobile cart in a busy waiting area allows each person to retrieve the information they want at their time of need. Conclusions. This supports the individualized teaching provided by patients’ doctors, nurses, and other members of the multidisciplinary team.     

Quality of Life of Caregivers of Very Low–Birthweight Infants

ABSTRACT: Background: The health and developmental outcomes of very low–birthweight infants are unpredictable over the first year of life. This uncertainty may have meaningful consequences for parents’ quality of life. The objective of this study was to explore the quality of life of caregivers of these infants. Methods: Primary caregivers of very low–birthweight infants, 12 to 18 months old, who had been cared for in an inner‐city hospital were enrolled in the study. Primary caregivers of full‐term infants of the same age served as a comparison group. During a telephone survey, participants answered questions about their quality of life, mental and physical health, living arrangements, and child’s health. Results: Eighty‐three caregivers of very low–birthweight infants and 84 caregivers of full‐term infants were enrolled in the study. Demographic characteristics of the caregivers were similar between the groups. Forty‐five percent of caregivers of very low–birthweight infants reported that their child had an ongoing medical problem compared with 23 percent of caregivers of full‐term infants. Both groups of caregivers reported significant physical and mental health problems. Caregivers of very low–birthweight infants reported higher quality of life than did caregivers of full‐term infants, but the difference did not reach statistical significance. Conclusions: Although very low–birthweight infants had poorer health and required significantly more health care resources than full‐term infants, caregivers’ quality of life did not differ between the two groups. Caregivers of both groups of infants reported substantial mental and physical health problems but perceived good quality of life. These data will aid parents, physicians, and policy makers as they struggle to make decisions concerning care of high‐risk, costly, very low–birthweight infants. (BIRTH 35:3 September 2008)     

Motoneuron excitability and muscle spasms are regulated by 5-HT2B and 5-HT2C receptor activity

Immediately after spinal cord injury (SCI), a devastating paralysis results from the loss of brain stem and cortical innervation of spinal neurons that control movement, including a loss of serotonergic (5-HT) innervation of motoneurons. Over time, motoneurons recover from denervation and function autonomously, exhibiting large persistent calcium currents (Ca PICs) that both help with functional recovery and contribute to uncontrolled muscle spasms. Here we systematically evaluated which 5-HT receptor subtypes influence PICs and spasms after injury. Spasms were quantified by recording the long-lasting reflexes (LLRs) on ventral roots in response to dorsal root stimulation, in the chronic spinal rat, in vitro. Ca PICs were quantified by intracellular recording in synaptically isolated motoneurons. Application of agonists selective to 5-HT(2B) and 5-HT(2C) receptors (including BW723C86) significantly increased the LLRs and associated Ca PICs, whereas application of agonists to 5-HT(1), 5-HT(2A), 5-HT(3), or 5-HT(4/5/6/7) receptors (e.g., 8-OH-DPAT) did not. The 5-HT(2) receptor agonist-induced increases in LLRs were dose dependent, with doses for 50% effects (EC(50)) highly correlated with published doses for agonist receptor binding (K(i)) at 5-HT(2B) and 5-HT(2C) receptors. Application of selective antagonists to 5-HT(2B) (e.g., RS127445) and 5-HT(2C) (SB242084) receptors inhibited the agonist-induced increase in LLR. However, antagonists that are known to specifically be neutral antagonists at 5-HT(2B/C) receptors (e.g., RS127445) had no effect when given by themselves, indicating that these receptors were not activated by residual 5-HT in the spinal cord. In contrast, inverse agonists (such as SB206553) that block constitutive activity at 5-HT(2B) or 5-HT(2C) receptors markedly reduced the LLRs, indicating the presence of constitutive activity in these receptors. 5-HT(2B) or 5-HT(2C) receptors were confirmed to be on motoneurons by immunolabeling. In summary, 5-HT(2B) and 5-HT(2C) receptors on motoneurons become constitutively active after injury and ultimately contribute to recovery of motoneuron function and emergence of spasms.