Variations in Genes Related to Sleep Patterns in Children With Autism Spectrum Disorder.

BACKGROUND: Sleep disturbance is a frequent comorbidity in children with autism spectrum disorder (ASD), affecting an estimated 40-80% of cases. Previous reports have shown relationships between several circadian rhythm-related genes and sleep problems in ASD. The purpose of the present study was to relate variation in and around melatonin synthesis and suprachiasmatic nucleus genes to sleep problems in a large sample of children with ASD. METHOD: This secondary analysis used existing genotypic and phenotypic data for 2,065 children, aged 4-18 years, from the Simons Simplex Collection (SSC). Sleep problems were measured with the SSC Sleep Interview. Expression quantitative trait loci and single nucleotide polymorphisms in 25 circadian genes were chosen primarily for their impact on expression levels of target genes in the brain. Associations between variants and composite sleep problems, nighttime problems, daytime problems, and sleep duration problems were calculated using logistic regression analysis. Age, sex, nonverbal IQ, ASD severity, gastrointestinal distress, seizures, and ancestry were included as covariates. Transmission disequilibrium tests were performed to test for overtransmission of alleles in the same variants. RESULTS: No significant associations or transmission disequilibrium were found between gene variants and sleep problems in this sample of children with ASD. CONCLUSION: Variation in expression of investigated genes in the melatonin synthesis and suprachiasmatic nucleus pathways did not have notable impacts on sleep problems in this large sample of children with ASD. Future research could explore translational and posttranslational effects of these genes or the effects of genes in other sleep-homeostasis pathways on sleep patterns.

Human Leukocyte Antigen Shared Epitope and Inflammation, Cardiovascular Disease, Cancer, and Mortality Among Postmenopausal Women in the Women's Health Initiative Rheumatoid Arthritis Study.

Specific alleles of the human leukocyte antigen (HLA)-DRB1 gene (HLA-DRB1) encode a "shared epitope" (SE) associated with rheumatoid arthritis (RA), especially more severe cyclic-citrullinated peptide antibody-positive (anti-CCP+) RA. We evaluated associations of number of SE alleles (0, 1, or 2) with total and cardiovascular disease (CVD) mortality and incident coronary heart disease (CHD), CVD, and cancer over a mean 8.9 (standard deviation, 3.5) years of follow-up, stratifying by baseline anti-CCP status (positive (+) vs. negative (-)). A longitudinal study, the Women's Health Initiative RA Study (1993-2010), sampled postmenopausal women who reported RA at baseline (1993-1998) or follow-up in the Women's Health Initiative, classified as anti-CCP+ RA (n = 556) or anti-CCP- non-RA (n = 1,070). Among anti-CCP+ RA women, SE alleles were not related to age-adjusted risks of CHD, CVD, or cancer or to total or CVD mortality. Among anti-CCP- non-RA women, age-adjusted hazard ratios for 1 and 2 SE alleles versus 0 SE alleles were 0.41 (95% confidence interval (CI): 0.34, 0.50) and 0.44 (95% CI: 0.27, 0.72), respectively, for CVD; 0.43 (95% CI: 0.37, 0.53) and 0.30 (95% CI: 0.16, 0.64), respectively, for CHD; and 0.62 (95% CI: 0.53, 0.73) and 0.52 (95% CI: 0.33, 0.83), respectively, for cancer. Associations persisted after adjustment for CVD risk factors, joint pain, rheumatoid factor positivity, and inflammatory markers (white blood cell count or cytokine level). In future studies, investigators should evaluate SE associations among anti-CCP- adults without RA and potential mechanisms.

Experiences of Parish Nurses in Providing Diabetes Education and Preconception Counseling to Women With Diabetes.

OBJECTIVE: To explore the role and experiences of the parish nurse in providing diabetes education and preconception counseling to women with diabetes. DESIGN: Mixed-methods concurrent embedded design. SETTING: Focus groups of community-based parish nurses accessed from a regional database (Pennsylvania, Florida, Ohio, New York, Arizona, and Minnesota). PARTICIPANTS: Forty-eight parish nurses recruited from the Parish Nurse and Health Ministry Program database in Western Pennsylvania. METHODS: The primary method was focus groups using face-to-face, teleconference, and videoconferencing formats. A secondary method used a quantitative descriptive design with three self-report measures (demographic, preconception counseling self-efficacy, and preconception counseling knowledge). Qualitative content analysis techniques were conducted and combined with descriptive analysis. RESULTS: Forty-eight parish nurses participated in 1 of 11 focus groups. Eight qualitative themes emerged: Awareness, Experience, Formal Training, Usefulness, Willingness, Confidence, "Wise Women," and Preconception Counseling Tool for Patients. Participants provided recommendations for training and resources to increase their knowledge and skills. Parish nurses' knowledge scores were low (mean = 66%, range = 40%-100%) with only moderate levels of self-efficacy (mean = 99, range = 27-164). Self-efficacy had a significantly positive association with knowledge (r = .29, p = .05). CONCLUSION: Quantitative results were consistent with participants' qualitative statements. Parish nurses were unaware of preconception counseling and lacked knowledge and teaching self-efficacy as it related to preconception counseling and diabetes education. Understanding parish nurses' experiences with women with diabetes and identifying their needs to provide education and preconception counseling will help tailor training interventions that could affect maternal and fetal outcomes.

Primer in Genetics and Genomics, Article 1: DNA, Genes, and Chromosomes.

Precision medicine refers to the practice of determining a patient's unique genetic, biomarker, and other characteristics for the purpose of improving his or her clinical outcomes. Not all patients with the same clinical diagnosis respond equally to identical treatment regimens. By examining patients at the molecular level, health-care providers will be better able to apply the most effective therapies that each individual requires. To understand precision medicine, nurses must have a solid understanding of genomics and proteomics. The purpose of this article is to (1) provide a historical review of what and how we have learned about the genome, particularly in the past century, (2) explain the processes whereby genetic information in cellular DNA is transcribed to messenger RNA and translated to protein, and (3) introduce genetic and epigenetic mechanisms that regulate gene expression.

Health beliefs among individuals at increased familial risk for type 2 diabetes: implications for prevention.

AIM: To evaluate perceived risk, control, worry, and severity about diabetes, coronary heart disease (CHD) and stroke among individuals at increased familial risk of diabetes. METHODS: Data analyses were based on the Family Healthware™ Impact Trial. Baseline health beliefs were compared across three groups: (1) no family history of diabetes, CHD or stroke (n=836), (2) family history of diabetes alone (n=267), and (3) family history of diabetes and CHD and/or stroke (n=978). RESULTS: After adjusting for age, gender, race, education and BMI, scores for perceived risk for diabetes (p<0.0001), CHD (p<0.0001) and stroke (p<0.0001) were lowest in Group 1 and highest in Group 3. Similar results were observed about worry for diabetes (p<0.0001), CHD (p<0.0001) and stroke (p<0.0001). Perceptions of control or severity for diabetes, CHD or stroke did not vary across the three groups. CONCLUSIONS: Among individuals at increased familial risk for diabetes, having family members affected with CHD and/or stroke significantly influenced perceived risk and worry. Tailored lifestyle interventions for this group that assess health beliefs and emphasize approaches for preventing diabetes, as well as its vascular complications, may be an effective strategy for reducing the global burden of these serious but related chronic disorders.

Variants of the adenosine A(2A) receptor gene are protective against proliferative diabetic retinopathy in patients with type 1 diabetes.

AIMS: The adenosine A(2A) receptor (ADORA(2A)) may ameliorate deleterious physiologic effects associated with tissue injury in individuals with diabetes. We explored associations between variants of the ADORA(2A) gene and proliferative diabetic retinopathy (PDR) in a cohort of patients with type 1 diabetes (T1D). METHODS: The participants were from the Pittsburgh Epidemiology of Diabetes Complications prospective study of childhood-onset T1D. Stereoscopic photographs of the retinal fundus taken at baseline, then biennially, for 10 years were used to define PDR according to the modified Airlie House system. Two tagging single nucleotide polymorphisms (tSNPs; rs2236624-C/T and rs4822489-G/T) in the ADORA(2A) gene were selected using the HapMap (haplotype map) reference database. RESULTS: A significant association was observed between SNP rs2236624 and PDR in the recessive genetic model. Participants homozygous for the T allele displayed a decreased risk of developing prevalent PDR (odds ratio, OR = 0.36; p = 0.04) and incident PDR (hazard ratio = 0.156; p = 0.009), and for all cases of PDR combined (OR = 0.23; p = 0.001). The protective effect of T allele homozygosity remained after adjusting for covariates. Similarly, for SNP rs4822489, an association between PDR and T allele homozygosity was observed following covariate adjustment (OR = 0.55; 95% CI: 0.31-0.92; p = 0.04). CONCLUSION: Genetic variants of ADORA(2A) offer statistically significant protection against PDR development in patients with T1D.

Microarray technology applied to the complex disorder of preeclampsia.

Preeclampsia is a life-threatening perinatal complication with unknown etiology. Microarray technology has characterized global gene expression in complex disorders such as preeclampsia. Nursing research and future practice may incorporate findings from microarray analyses to identify susceptibility to and prevent disease, to diagnose early, and to design and monitor personalized therapies. This overview of microarray technology, with emphasis on how it can inform genomics of preeclampsia, may provide concepts to improve future maternal-neonatal nursing care.

Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than nondiabetic women.

OBJECTIVE: To determine whether middle-aged premenopausal women with type 1 diabetes had more self-reported fractures and lower bone mineral density (BMD) compared with nondiabetic women. RESEARCH DESIGN AND METHODS: Participants were premenopausal women aged 35-55 years with type 1 diabetes (n = 67; 32.2 +/- 5.3 years duration) and without diabetes (n = 237). Total hip, femoral neck, whole-body, and spine BMD were measured by dual X-ray absorptiometry. Calcaneal broadband ultrasound attenuation (BUA) was assessed with quantitative ultrasound. RESULTS: Women with type 1 diabetes were more likely to report a fracture after age 20 years compared with nondiabetic women (33.3 vs. 22.6%; age-adjusted odds ratio 1.89 [95% CI 1.02-3.49]). Type 1 diabetes was associated with lower total hip BMD (0.890 vs. 0.961 g/cm2; P < 0.001), femoral neck BMD (0.797 vs. 0.847 g/cm2; P = 0.001), whole-body BMD (1.132 vs. 1.165 g/cm2; P < 0.01), and lower calcaneal BUA (71.6 vs. 84.9 dB/MHz; P < 0.001) after multivariate adjustment. BMD was 3-8% lower in type 1 diabetic compared with control women and calcaneal BUA was 15% lower. Spine BMD and biomarkers of bone remodeling were not significantly different between groups. In the type 1 diabetic women, reduced monofilament detection and blindness were both associated with lower BMD. CONCLUSIONS: Lower BMD in premenopausal women with type 1 diabetes may substantially increase their risk of developing osteoporosis after menopause. Type 1 diabetic women should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause.

Developing research competence to support evidence-based practice.

This article describes one step in the process that was undertaken to prepare for the introduction of evidence-based practice (EBP) into the curriculum across the Bachelor of Science in Nursing, Master of Science in Nursing, and Doctor of Philosophy programs, as well as the programs that were under development, Clinical Nurse Leader and Doctor of Nursing Practice, at the University of Pittsburgh School of Nursing. Expected research competencies were identified for each level or academic year within each program. Based on these competencies, recommendations on how to modify the curriculum into one that would support students' acquisition and development of the skills necessary to be successful in matriculating through an EBP curriculum were developed. Evaluation mechanisms for the achievement of these competencies vary across the academic programs and will include performance on capstone projects, comprehensive examinations, and program milestones for doctoral students. The establishment of evidence-based competencies provided a foundation for the development of new teaching approaches and the curricular revisions across the three academic programs. Thus, the University of Pittsburgh model of educating for EBP is based on a sequential layering of research competencies throughout the curriculum.

Epidemics of type 1 diabetes in China.

OBJECTIVE: The aim of this study was to search for the seasonal and geographic variations in epidemics of type 1 diabetes in China. RESEARCH DESIGN AND METHODS: Incidence data from 22 type 1 diabetes registration centers across China were analyzed. A Poisson regression model with a sine wave function was applied to evaluate the seasonal trends. A scan statistic was used to examine the occurrence of an epidemic. RESULTS: There was a significant cyclic trend of incidence of type 1 diabetes in China. The northern area had a higher incidence rate than the southern area. Epidemics were discovered in Dalian and Shenyang from late 1992 to late 1993. CONCLUSIONS: There was a strong association of climate and incidence of type 1 diabetes in China, whereby the incidence was higher in the colder areas and in the winter months. Evidence of epidemics existed in two centers in 1992--1993. It is critical to identify the epidemics early and determine the causes of epidemics.

Infant diet and type 1 diabetes in China.

Infant milk and food introduction may be linked to type 1 diabetes risk in high incidence populations. Dietary data through age 12 months was collected for 247 type 1 diabetic cases and 443 controls in China, a low incidence population, to determine if milk and solid food intake differed. Age range at introduction to milk and formulas was similar in cases and controls but solid food introduction more often occurred before age 3 months in cases. Logistic regression analyses showed soy milk formula consumption at 4-6 (OR = 2.0; 95% CI: 1.1-3.4) and 7-12 months of age (OR = 1.5; 95% CI: 1.0-2.1) was associated with a twofold higher risk of type 1 diabetes, while steamed bread consumption (4-6 months, OR = 0.44; 95% CI: 0.28-0.68; 7-12 months, OR = 0.48; 95% CI: 0.34-0.69) and higher SES (4-6 months, OR = 0.55; 95% CI: 0.39-0.78; 7-12 months, OR = 0.57; 95% CI: 0.40-0.83) were negatively associated. Drinking cow's milk at 7-12 months (OR = 0.60; 95% CI: 0.43-0.85) was negatively associated with type 1 diabetes while consuming vegetables at 4-6 months (OR = 1.5; 95% CI: 1.0-2.2) was positively associated. Results suggest that infant milk and solid food intake are associated with type 1 diabetes in China. Prospective studies may determine how these dietary factors impact disease etiology, particularly for at-risk-populations.

Genetics and type 1 diabetes: online resources for diabetes educators.

PURPOSE: Genetic education Internet sites and peer-reviewed medical literature were reviewed and critiqued to develop tables summarizing online resources for diabetes health professionals. METHODS: Using Internet search engines, each Web site identified for this project met the following criteria: (1) accurate and valid site content based on widely accepted genetic texts, (2) credibility of the organization that maintained the Web site, (3) ease of navigation, and (4) provision of continuing education credits. PubMed was used to find journal articles using similar criteria. RESULTS: There were 33 Web sites on genetic education for diabetes health professionals that met the inclusion criteria. The literature search identified 36 articles regarding the importance of genetic education for nurses and other health professionals, as well as information regarding genetics and diabetes. CONCLUSIONS: Valid and credible information on genetics and type 1 diabetes is available for diabetes health professionals on the Internet and in the medical literature.

Genetics and type 1 diabetes: online resources for patients.

PURPOSE: This Web-based review was undertaken to compile online resources for diabetes educators on genetics--specifically, the genetics of type 1 diabetes--and to provide helpful and accurate information for the public. METHODS: Keyword searches were performed to identify Web sites for genetics education for the lay public and for sites specifically geared toward children/young adults. Web sites were critiqued based on credibility (source, currency, relevance/utility), content (accuracy), and design (accessibility, logical organization). Additional keyword searches were conducted to find sites describing the genetics of type 1 diabetes, which were evaluated for content validity. RESULTS: The Web sites selected for general genetics education contain accessible, credible, and accurate information about basic genetics in an easy-to-follow format with both text and visual aides. Although these sites adequately educate the public about genetics, only diabetes-specific Web sites discussed the relationship between genetics and risk for type 1 diabetes associated with high-risk HLA alleles. CONCLUSIONS: In this genomic age, it is important for healthcare professionals to provide genetics information. Educational tools that specifically address the genetics of type 1 diabetes are urgently needed to fill the current information gaps on the Internet.

Incidence of ESRD and survival after renal replacement therapy in patients with type 1 diabetes: a report from the Allegheny County Registry.

BACKGROUND: Little information is available regarding the long-term incidence of end-stage renal disease (ESRD) and survival after the introduction of renal replacement therapy (RRT) in patients with type 1 diabetes. METHODS: We studied 1,075 patients with type 1 diabetes (onset age < 18 years) diagnosed between 1965 and 1979, who comprise the Allegheny County population-based registry. Onset of ESRD was defined as the introduction of RRT (dialysis or transplantation). RESULTS: Of 1,075 registrants, the living status of 975 patients (90.7%) and complication status of 798 patients (74.2%) were ascertained as of January 1, 1999. During the observation period, 104 patients (13.0%) developed ESRD, for an incidence rate of 521/100,000 person-years (95% confidence interval, 424 to 629). The cumulative incidence of ESRD was 11.3% at 25 years of diabetes. A significant decline was observed in 20-year cumulative incidence rates of ESRD for patients diagnosed between 1965 and 1969, 1970 and 1974, and 1975 and 1979 (9.1%, 4.7%, and 3.6%, respectively; P = 0.006). Of 104 patients with ESRD, 29 patients (28%) received dialysis alone, 44 patients (42%) received dialysis followed by kidney transplantation, 26 patients (25%) underwent successful transplantation alone, and 5 patients (5%) underwent a failed kidney transplantation followed by dialysis therapy. The cumulative survival rate 10 years after the introduction of RRT was 51.2%. The cumulative survival rate of dialysis therapy followed by kidney transplantation was significantly greater than that of dialysis therapy alone (P < 0.001). No difference was detected in survival between pancreas-kidney transplant recipients and kidney-alone transplant recipients (P = 0.7). CONCLUSION: The incidence of ESRD observed in this cohort has declined, probably reflecting the better glycemic and blood pressure control available since the early 1980s.

Menstrual cycle differences between women with type 1 diabetes and women without diabetes.

OBJECTIVE: To evaluate menstrual cycle histories among women with type 1 diabetes, their sisters, and unrelated control subjects without diabetes across all reproductive ages. RESEARCH DESIGN AND METHODS: Menstrual and reproductive histories were obtained by questionnaire from 143 women with type 1 diabetes, 186 sisters without diabetes, and 158 unrelated control subjects without diabetes participating in the Familial Autoimmune and Diabetes study. RESULTS: Women with type 1 diabetes had more menstrual problems (long cycles, long menstruation, and heavy menstruation) before age 30 years than sisters and control subjects. These differences were all statistically significant, except for heavy menstruation at age <20 years. No differences were observed after age 30 years. Women with type 1 diabetes experienced later menarche, earlier natural menopause, fewer pregnancies, and more stillbirths than women without diabetes. Multiple regression analyses revealed that type 1 diabetes caused an approximate twofold increased risk of any menstrual problem before age 30 years. These were primarily related to long cycles and long menstruation in women aged <20 and 20-29 years, as well as with heavy menstruation from 20 to 29 years. Oral contraceptives were protective for any menstrual problem and heavy menstruation from 30 to 39 years of age. With history of pregnancy from 20 to 40 years of age, any menstrual problem and long menstruation were more likely. CONCLUSIONS: The results suggest that type 1 diabetes is an independent risk factor for menstrual disturbances in young adults. Future studies may determine whether addressing menstrual disturbances improves quality of life and health for these women.

Duration of breast feeding and bovine serum albumin antibody levels in type 1 diabetes: a case-control study.

OBJECTIVE: To compare the levels of bovine serum albumin (BSA) antibodies and their relationship with duration of breast feeding, age of exposure to cow's milk, and human leukocyte antigen (HLA-DQ) genotype in children with and without type 1 diabetes. METHODS: Serum samples from 143 (0.3-14.7 yr) newly diagnosed children with type 1 diabetes and 107 unrelated control children (0.8-13.5 yr) were evaluated for BSA antibodies. Duration of breast feeding and exposure to cow's milk were recorded on questionnaires. HLA-DQ typing was determined by polymerase chain reaction. RESULTS: One hundred percent of the diabetic children were positive for BSA antibodies compared to 1.9% for healthy controls (p < 0.001). Diabetic children also had higher levels of immunoglobulin G antibodies than unrelated controls (55.1 vs. 17.8 ng/mL, p < 0.0001). Duration of breast feeding (5.4 vs. 7.6 months, p < 0.02), but not age of exposure to cow's milk (8.3 vs. 9.2 months, p = 0.11), differed between cases and controls. There was no difference in antibody titer by duration of breast feeding or age of exposure to cow's milk in the cases or controls. CONCLUSION: Higher levels of antibodies to BSA were found in children recently diagnosed with type 1 diabetes compared to the controls, particularly those with high or moderate HLA-DQ genotypes. The BSA profile, however, does not seem to depend on duration of breast feeding or age of exposure to cow's milk in this population.

HLA-DQ genotypes in classic type 1 diabetes and in latent autoimmune diabetes of the adult.

In 1993-1996, islet autoantibodies, C-peptide, and HLA-DQ genotypes were evaluated in 345 insulin-treated diabetic patients of all ages from the Skaraborg Diabetes Registry 5-6 years after their diagnosis and in 216 control subjects from the Skaraborg County, Sweden, population. The aims of this study were to clarify the importance of age at diagnosis of diabetes for HLA-DQ associations in patients with classic type 1 diabetes and whether patients considered to have latent autoimmune diabetes of the adult differed in their human leukocyte antigen (HLA) associations. An abnormally low fasting C-peptide value was used as the definition of type 1 diabetes, found in 182 of 345 (53%) patients. No major associations between age at diagnosis and HLA susceptibility or protective genotypes were detected in type 1 diabetic patients. Among the 163 patients with preserved beta-cell function, the frequency of HLA protective genotypes was clearly decreased (5% vs. 42%) in the 46 of 163 with islet antibodies compared with the 117 of 163 antibody-negative patients. The authors conclude that there were no major effects of age at diagnosis on HLA-DQ associations in classic type 1 diabetic patients, whereas lack of HLA-DQ protective genotypes was a feature of patients with slow-progressing type 1 diabetes (latent autoimmune diabetes of the adult).

Molecular epidemiology: the impact of molecular biology in epidemiology research

Progress in molecular biology and genetics is changing the practice of medicine and public health through the development of molecular diagnostics and targeted interventions for susceptible individuals. The ethical, legal and social issues that are becoming apparent as these important discoveries are introduced into practice will have an enormous impact on society. The accurate translation of this new genetic information from the laboratory to the community is an urgent need. Molecular epidemiology is at the foundation of this important link, and represents the scientific basis of public health for the 21st Century