CHRNA5 and CHRNA3 variants and level of neuroticism in young adult Mexican American men and women

A lifetime history of alcohol dependence has been associated with elevations in neuroticism in Mexican American young adults. The identification of genetic markers associated with neuroticism and their influence on the development of alcohol use disorders (AUD) may contribute to our understanding of the relationship between personality traits and the increased risk of AUD in Mexican Americans. The purpose of this study was to investigate associations between neuroticism and 13 single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine (nAChR) α5-subunit (CHRNA5) and α3-subunit (CHRNA3) genes in young adult Mexican American men and women. Participants were four hundred sixty-five young adult Mexican American men and women who are literate in English and are residing legally in San Diego County. Each participant gave a blood sample and completed a structured diagnostic interview. Neuroticism was assessed using the Maudsley Personality Inventory. The minor alleles of four CHRNA5 polymorphisms (rs588765, rs601079, rs680244 and rs555018) and three CHRNA3 polymorphisms (rs578776, rs6495307 and rs3743078) showed associations with neuroticism. Several of these SNPs also displayed nominal associations with DSM-IV alcohol and nicotine dependence, but tests of mediation suggested that these relations could be partially explained by the presence of co-occurring neuroticism. These findings suggest that genetic variations in nicotinic receptor genes may influence the development of neuroticism, which in turn is involved in the development of AUDs and nicotine dependence in Mexican American young adults

A Barrier to Exclusive Breastfeeding for Wic Enrollees: Limited Use of Exclusive Breastfeeding Food Package for Mothers

Background: In the first 2 weeks of life, most breastfeeding mother–infant dyads in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) receive infant formula from WIC, instead of a larger food package designed for exclusively breastfeeding mothers. This study was designed to explore reasons for high rates of formula supplementation of breastfeeding newborns enrolled in WIC and the limited use of the WIC expanded food package. Methods: We conducted in-depth interviews with 29 mothers who either partially or exclusively breastfed for at least 2 months. Interviews were transcribed verbatim, analyzed, coded, and organized into 10 themes. Results: Participants view the WIC program in a contradictory manner. They see it as highly supportive of breastfeeding, but also as a promoter of infant formula. The expanded food package for mothers is not valued, but free supplemental formula is highly valued. Misinformation about breastfeeding pervades the healthcare system, and exclusive breastfeeding is not promoted as an important health goal. Lack of access to breast pumps, the unacceptability of pumping in the workplace, and difficulties with nursing in public all contribute to formula supplementation. Conclusions: The healthcare system, the WIC program, and demands of daily life all contribute to low rates of exclusive breastfeeding in the WIC program. The available expanded food package for mothers who are exclusively breastfeeding is both disliked and underutilized, while free supplemental formula is rarely discouraged

Global Environmental Change: What Can Health Care Providers and the Environmental Health Community Do About It Now?

The debate about whether global environmental change is real is now over; in its wake is the realization that it is happening more rapidly than predicted. These changes constitute a profound challenge to human health, both as a direct threat and as a promoter of other risks. We call on health care providers to inform themselves about these issues and to become agents of change in their communities. It is our responsibility as clinicians to educate patients and their communities on the connections between regressive policies, unsustainable behaviors, global environmental changes, and threats to health and security. We call on professional organizations to assist in educating their members about these issues, in helping clinicians practice behavior change with their patients, and in adding their voices to this issue in our statehouses and Congress. We call for the development of carbon- and other environmental-labeling of consumer products so individuals can make informed choices; we also call for the rapid implementation of policies that provide tangible economic incentives for choosing environmentally sustainable products and services. We urge the environmental health community to take up the challenge of developing a global environmental health index that will incorporate human health into available “planetary health” metrics and that can be used as a policy tool to evaluate the impact of interventions and document spatial and temporal shifts in the healthfulness of local areas. Finally, we urge our political, business, public health, and academic leaders to heed these environmental warnings and quickly develop regulatory and policy solutions so that the health of populations and the integrity of their environments will be ensured for future generations

Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis.

Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility

Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a Native American community sample

Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism

Factor XII and Upar Upregulate Neutrophil Functions to Influence Wound Healing

Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12–/–) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor–mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474). Downstream of pAkt2S474, FXII stimulation of neutrophils upregulated surface expression of αMβ2 integrin, increased intracellular calcium, and promoted extracellular DNA release. The sum of these activities contributed to neutrophil cell adhesion, migration, and release of neutrophil extracellular traps in a process called NETosis. Decreased neutrophil signaling in F12–/– mice resulted in less inflammation and faster wound healing. Targeting hepatic F12 with siRNA did not affect neutrophil migration, whereas WT BM transplanted into F12–/– hosts was sufficient to correct the neutrophil migration defect in F12–/– mice and restore wound inflammation. Importantly, these activities were a zymogen FXII function and independent of FXIIa and contact activation, highlighting that FXII has a sophisticated role in vivo that has not been previously appreciated

Psychometric properties of the Chinese quality of life instrument (HK version) in Chinese and Western medicine primary care settings

Background: The Chinese Quality of Life Measure (ChQOL) had only been validated on a small number of selected subjects in Hong Kong and had never been tested in the Western medicine (WM) primary care setting. Aims: and objectives To test the psychometrics properties of ChQOL(HK version) in both TCM and WM general outpatient clinics. Methods: Three samples of Chinese adult patients [(1) 569 consulting TCM clinics for episodic illnesses; (2) 524 consulting WM clinics for episodic illnesses; (3) 205 consulting WM clinics for chronic disease follow-up] in Hong Kong were invited to complete the ChQOL(HK version) and the SF-36 Health Survey during their consultations and 2 weeks after consultations. The scaling assumptions, factor structure, convergent construct validity, reliability, responsiveness, and discriminatory power of the ChQOL were evaluated. Results: Majority of items satisfied the scaling assumptions. A two instead of 3-factor structure was found with physical form and emotion facets loading on one factor. Convergent construct validity was confirmed with moderate correlations with SF-36 scores. Internal consistency and test-retest reliability were satisfactory. The ChQOL(HK version) was able to detect significant improvements 2 weeks after consultations, and it was able to discriminate between groups with different illness severity, age, and sex. Conclusion The ChQOL(HK version) was shown to have satisfactory validity, reliability, discriminatory power, and responsiveness in both TCM and Western medicine primary care settings. The validity of the 3-domain scaling structure needs further evaluation. © The Author(s) 2011.published_or_final_versionSpringer Open Choice, 21 Feb 201

The Rat Genome Database (RGD): developments towards a phenome database

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms

Needs and preferences for psychological interventions of people with motor neuron disease

Background: There is a lack of knowledge about what factors may impede or facilitate engagement in psychological interventions in people with motor neuron disease (pwMND) and how such interventions can be adapted to best meet the needs of this population. Objectives: To explore the needs and preferences of pwMND with respect to psychological interventions, and how best to adapt such interventions for pwMND. Methods: A series of semi-structured interviews (n = 22) and workshops (n = 3) were conducted with pwMND (n = 15), informal caregivers of pwMND (n = 10), and MND healthcare professionals (n = 12). These explored preferences and concerns that would need to be considered when delivering a psychological intervention for pwMND. Three areas were explored: (i) perceived factors that may hinder or facilitate pwMND engaging with psychological interventions; (ii) ways in which such interventions could be adapted to meet the individual needs of pwMND; and (iii) views regarding the main psychological issues that would need to be addressed. Workshops and interviews were audio recorded and transcribed and thematic analysis was used to inductively derive themes. Findings: Data could be classified within four overarching themes: unfamiliar territory; a series of losses; variability and difficulty meeting individual needs; and informal support. Conclusions: Flexibility, tailoring interventions to the individual needs of pwMND, and encouraging autonomy are key attributes for psychological interventions with pwMND. Psychological interventions such as Acceptance and Commitment Therapy (ACT) could be acceptable for pwMND if adapted to their specific needs