Creating a Culture of Mental Health in Filipino Immigrant Communities through Community Partnerships

One out of five children in the United States has a mental, emotional, or behavioral health diagnosis. Behavioral health issues cost America $247 billion per year and those with mental health disorders have poorer health and shorter lives. Evidence-based parenting interventions provided in childhood have proven to be effective in helping parents to prevent disruptive, oppositional and defiant behaviors, anxiety and depressive symptoms, tobacco, alcohol, and drug misuse, aggression, delinquency, and violence. Yet, few parents participate in such programs, especially hard-to-reach, underserved minority and immigrant populations. The Robert Wood Johnson Foundation has identified a culture of health action framework that mobilizes individuals, communities, and organizations in order to examine ways to improve systems of prevention, invest in building the evidence base for such systems, and provide evidence-based information to decision makers. The overarching goal of this effort was to create a culture of mental health among Filipinos, a large, yet understudied immigrant community that is affected by alarming mental health disparities, including high rates of adolescent suicide ideation and attempts. Our impact project focused on increasing the reach of the Incredible Years® because maximizing the participation of high-risk, hard-to-engage populations may be one of the most important ways to increase the population-level impact of evidence-based parenting programs. If the approach succeeded with Filipinos, comparable strategies could be used to effectively reach other underserved populations in the U.S., many of whom are reluctant to seek behavioral health services. In this chapter we discuss 1) the state of the literature on the topic of Filipino adolescent mental health disparities; 2) our wicked problem and the impact project aimed at ameliorating this issue; 3) how our team formed and implemented our impact project; 4) outcomes and results of our efforts; 5) challenges we faced and how they were overcome; 6) the leadership and health equity skills that were most helpful in addressing our problem; and 7) a toolkit that could assist other communities addressing youth mental health and prevention of suicide and depression

Developmental changes in food perception and preference

Food choices are a key determinant of dietary intake, with brain regions, such as the mesolimbic and prefrontal cortex maturing at differential rates into adulthood. More needs to be understood about developmental changes in healthy and unhealthy food perceptions and preference. We investigated how food perceptions and preference vary as a function of age and how food attributes (taste and health) impact age-related changes. One hundred thirty-nine participants (8–23 years, 60 females) completed computerized tasks to rate high-calorie and low-calorie food cues for taste, health, and liking (preference), followed by 100 binary food choices based on each participant’s ratings. Dietary self-control was considered successful when the healthier (vs. tastier) food was chosen. Self-control success ratio was the proportion of success trials over total number of choices. Beta-weights for health (β-health) and taste (β-taste) were calculated as each attribute’s influence on food preference. Adiposity measurements included BMI z-score and waist-to-height ratio (WHtR). High-calorie foods were rated more tasty and less healthy with increasing age. Older participants liked high-calorie foods more (vs. younger participants), and β-taste was associated with age. Significant age-by-WHtR interactions were observed for health and taste ratings of high-calorie foods, β-taste, and marginally for preference of high-calorie foods. Stratifying by WHtR (high, low), we found age-related increases in taste and preference ratings of high-calorie foods in the high WHtR group alone. In contrast, age-related decreases in health ratings of high-calorie foods were significant in the low WHtR group alone. Age and β-taste were significantly associated in the high WHtR group and only marginally significant with low WHtR. Although participants rated low-calorie foods as less tasty and less healthy with increasing age, there was no association between age and preference for low-calorie foods. Participants made faster food choices with increasing age regardless of WHtR, with a significant age-by-WHtR interaction on reaction time (RT). There were no age-related effects in self-control success ratio and β-health. These results suggest that individual differences in age and central adiposity play an important role in preference for high-calorie foods, and a higher importance of food tastiness in food choice may contribute to greater preference for high-calorie foods with increasing age

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Deletion at ITPR1 Underlies Ataxia in Mice and Spinocerebellar Ataxia 15 in Humans

We observed a severe autosomal recessive movement disorder in mice used within our laboratory. We pursued a series of experiments to define the genetic lesion underlying this disorder and to identify a cognate disease in humans with mutation at the same locus. Through linkage and sequence analysis we show here that this disorder is caused by a homozygous in-frame 18-bp deletion in Itpr1 (Itpr1Δ18/Δ18), encoding inositol 1,4,5-triphosphate receptor 1. A previously reported spontaneous Itpr1 mutation in mice causes a phenotype identical to that observed here. In both models in-frame deletion within Itpr1 leads to a decrease in the normally high level of Itpr1 expression in cerebellar Purkinje cells. Spinocerebellar ataxia 15 (SCA15), a human autosomal dominant disorder, maps to the genomic region containing ITPR1; however, to date no causal mutations had been identified. Because ataxia is a prominent feature in Itpr1 mutant mice, we performed a series of experiments to test the hypothesis that mutation at ITPR1 may be the cause of SCA15. We show here that heterozygous deletion of the 5′ part of the ITPR1 gene, encompassing exons 1–10, 1–40, and 1–44 in three studied families, underlies SCA15 in humans

A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice

Epstein-Barr virus (EBV), an oncogenic gammaherpesvirus, causes acute infectious mononucleosis (AIM) and is linked to the development of several human malignancies. There is an urgent need for a vaccine that is safe, prevents infection and/or limits disease. Unique among human herpesviruses, glycoprotein (gp)350/220, which initiates EBV attachment to susceptible host cells, is the major ligand on the EBV envelope and is highly conserved. Interaction between gp350/220 and complement receptor type 2 (CR2)/CD21 and/or (CR1)/CD35 on B-cells is required for infection. Potent antibody responses to gp350/220 occur in animal models and humans. Thus, gp350/220 provides an attractive candidate for prophylactic subunit vaccine development. However, in a recent Phase II clinical trial immunization with soluble recombinant gp350 reduced the incidence of AIM, but did not prevent infection. Despite various attempts to produce an EBV vaccine, no vaccine is licensed. Herein we describe a sub-unit vaccine against EBV based on a novel Newcastle disease virus (NDV)-virus-like particle (VLP) platform consisting of EBVgp350/220 ectodomain fused to NDV-fusion (F) protein. The chimeric protein EBVgp350/220-F is incorporated into the membrane of a VLP composed of the NDV matrix and nucleoprotein. The particles resemble native EBV in diameter and shape and bind CD21 and CD35. Immunization of BALB/c mice with EBVgp350/220-F VLPs elicited strong, long-lasting neutralizing antibody responses when assessed in vitro. This chimeric VLP is predicted to provide a superior safety profile as it is efficiently produced in Chinese hamster ovary (CHO) cells using a platform devoid of human nucleic acid and EBV-transforming genes

The Impact of Insulin Pump Therapy on Glycemic Profiles in Patients with Type 2 Diabetes: Data from the OpT2mise Study

Background: The OpT2mise randomized trial was designed to compare the effects of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) on glucose profiles in patients with type 2 diabetes. Research Design and Methods: Patients with glycated hemoglobin (HbA1c) levels of ≥8% (64 mmol/mol) and ≤12% (108 mmol/mol) despite insulin doses of 0.7-1.8 U/kg/day via MDI were randomized to CSII (n=168) or continued MDI (n=163). Changes in glucose profiles were evaluated using continuous glucose monitoring data collected over 6-day periods before and 6 months after randomization. Results: After 6 months, reductions in HbA1c levels were significantly greater with CSII (-1.1±1.2% [-12.0±13.1 mmol/mol]) than with MDI (-0.4±1.1% [-4.4±12.0 mmol/mol]) (P<0.001). Similarly, compared with patients receiving MDI, those receiving CSII showed significantly greater reductions in 24-h mean sensor glucose (SG) (treatment difference, -17.1 mg/dL; P=0.0023), less exposure to SG >180 mg/dL (-12.4%; P=0.0004) and SG >250 mg/dL (-5.5%; P=0.0153), and more time in the SG range of 70-180 mg/dL (12.3%; P=0.0002), with no differences in exposure to SG<70 mg/dL or in glucose variability. Changes in postprandial (4-h) glucose area under the curve >180 mg/dL were significantly greater with CSII than with MDI after breakfast (-775.9±1,441.2 mg/dL/min vs. -160.7±1,074.1 mg/dL/min; P=0.0015) and after dinner (-731.4±1,580.7 mg/dL/min vs. -71.1±1,083.5 mg/dL/min; P=0.0014). Conclusions: In patients with suboptimally controlled type 2 diabetes, CSII significantly improves selected glucometrics, compared with MDI, without increasing the risk of hypoglycemia

Characterization of the VVV Survey RR Lyrae Population across the Southern Galactic Plane

This is an author created, un-copyedited version of an article published in The Astronomical Journal. Under embargo. Embargo end date: 27 March 2018. IOP Publishing is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at doi: https://doi.org/10.3847/1538-3881/aa5be4.Deep near-IR images from the VISTA Variables in the Vía Láctea (VVV) Survey were used to search for RR Lyrae stars in the Southern Galactic plane. A sizable sample of 404 RR Lyrae of type ab stars was identified across a thin slice of the fourth Galactic quadrant (295° < ℓ < 350°, −2°.24 < b < −1°.05). The sample’s distance distribution exhibits a maximum density that occurs at the bulge tangent point, which implies that this primarily Oosterhoff type I population of RRab stars does not trace the bar delineated by their red clump counterparts. The bulge RR Lyrae population does not extend beyond ℓ ∼ 340°, and the sample’s spatial distribution presents evidence of density enhancements and substructure that warrants further investigation. Indeed, the sample may be employed to evaluate Galactic evolution models, and is particularly lucrative since half of the discovered RR Lyrae are within reach of Gaia astrometric observations.Peer reviewedFinal Accepted Versio

Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62552/1/nature06742.pd

The Variant rs1867277 in FOXE1 Gene Confers Thyroid Cancer Susceptibility through the Recruitment of USF1/USF2 Transcription Factors

In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30–1.70; P = 5.9×10−9). Functional assays of rs1867277 (NM_004473.3:c.−283G>A) within the FOXE1 5′ UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/αCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era