A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder

Background: Melanopsin, a non-visual photopigment, may play a role in aberrant responses to low winter light levels in Seasonal Affective Disorder (SAD). We hypothesize that functional sequence variation in the melanopsin gene could contribute to increasing the light needed for normal functioning during winter in SAD. Methods: Associations between alleles, genotypes, and haplotypes of melanopsin in SAD participants (n = 130) were performed relative to controls with no history of psychopathology (n = 90). Results: SAD participants had a higher frequency of the homozygous minor genotype (T/T) for the missense variant rs2675703 (P10L) than controls, compared to the combined frequencies of C/C and C/T. Individuals with the T/T genotype were 5.6 times more likely to be in the SAD group than the control group, and all 7 (5%) of individuals with the T/T genotype at P10L were in the SAD group. Limitations: The study examined only one molecular component of the non-visual light input pathway, and recruitment methods for the comparison groups differed. Conclusion: These findings support the hypothesis that melanopsin variants may predispose some individuals to SAD. Characterizing the genetic basis for deficits in the non-visual light input pathway has the potential to define mechanisms underlying the pathological response to light in SAD, which may improve treatment. © 2008 Elsevier B.V

Parents with Low Literacy Report Higher Quality of Well-Child Care

Introduction: The growing literature on improving pediatric quality of care has highlighted the gaps in quality by socioeconomic status. Literacy may be an important factor within the relationship between socioeconomic status and quality healthcare. As young children depend on their parents for healthcare services, we hypothesized that low parental literacy would be associated with poor well-child healthcare. Methods Our design was a cross-sectional survey using face-to-face interviews of caregivers of 1-4 year old children in a pediatric resident clinic in the Southeast. We used the Rapid Estimate of Adult Literacy in Medicine to assess parental literacy and four subscales relevant to either provider-parent relationships or content of discussions in the well-child visit from the Promoting Healthy Development Survey to assess the quality of the well-child appointment. Results The mean age of the 150 respondents was 30 years, 56% were African American, 68% received Medicaid, and 86% graduated high school. Thirty-four percent of the respondents scored below a 9th grade reading level (low literacy). Parents with low-literacy were more likely than those with normal or high literacy to report family centered care (55% versus 27%, p=0.001 ), and helpfulness and confidence (84% versus 56%, p<0.001 ). There was no difference, by literacy level, in the mean percent of family well-being topics discussed or the mean percent of anticipatory guidance topics for which the parents had their informational needs met. Discussion The low-literacy respondents reported higher quality than the normal/high literacy group regarding relationships and there was no difference in quality by literacy level regarding content of discussions. Potential mechanisms for the difference between low and high literacy groups include that parents with low-literacy may have lower expectations regarding relationships with their healthcare provider or pediatric residents may be more effective at relationship building with low-literacy families.Master of Public Healt

Primary Care Physicians’ Experience and Confidence with Genetic Testing and Perceived Barriers to Genomic Medicine

Purpose: Genetic testing is progressing towards use of patients’ genomes for personalized medicine. Primary care physicians (PCPs) may use genetic tests to screen and assess risk. However, PCPs’ current preparedness for the expanding integration of genetics into practice is uncharacterized. We examined primary care physicians’ perceptions of and experience with genetic testing. Methods: An anonymous survey was mailed to PCPs across three regional health networks querying opinions of, experience with, confidence in, and perceived barriers to genetic testing. Results: The survey response rate was 37.8%. Respondents believed learning about new genetic advances was important to clinical practice (67.0%). A minority (19.0%) had ordered genetic testing in six months, with cancer risk testing the most frequently ordered. Respondents were not confident in the skills required for using genetic testing in practice. Few respondents felt that they had time to counsel about genetic risk (9.5%) or that most patients could comprehend the concept of risk (27.0%). Conclusions: Primary care physicians had a high opinion of using genetic testing in medicine, but reported little experience or confidence incorporating genetic testing into practice. A majority perceived time constraints and patient comprehension as barriers. These data demonstrate a need for genetics educational resources for physicians and patients

Cardiac-restricted IGF-1Ea overexpression reduces the early accumulation of inflammatory myeloid cells and mediates expression of extracellular matrix remodelling genes after myocardial infarction

Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea) propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9), their inhibitors (TIMP-1 and TIMP-2), and collagen types (Col 1α1 and Col 1α3) in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function

Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism

The first computational approach for the rapid generation of genome-scale tissue-specific models from a generic species model.A genome scale model of human liver metabolism, which is comprehensively tested and validated using cross-validation and the ability to carry out complex hepatic metabolic functions.The model's flux predictions are shown to correlate with flux measurements across a variety of hormonal and dietary conditions, and are successfully used to predict biomarker changes in genetic metabolic disorders, both with higher accuracy than the generic human model