Mediation effects of diabetes and inflammation on the relationship of obesity to cognitive impairment in African Americans.

BACKGROUND: Whether diabetes and adipokine-driven inflammation explain the association of obesity to cognitive impairment is unknown. METHODS: Structural equation models estimated the total effects of waist circumference on cognitive outcomes among African American participants cross-sectionally (index exam) and longitudinally. Total effects were deconstructed into direct pathways of waist circumference to cognitive impairment and indirect mediation pathways through leptin, soluble tumor necrosis factor receptor 2 (sTNFR2), and diabetes. Waist circumference, leptin, and sTNFR2 were standardized. Cognitive impairment was defined as MMSE <21 or a z-score < -1.5 standard deviation (SD). Incident cognitive impairment was defined among those without cognitive impairment at the index exam as follow-up MMSE<21, z- score < -1.5, MMSE decline >1 point/year, or z-score decline of >0.1 SD/year. RESULTS: Among 1008 participants (70% women, mean age 62.9 years, 14.5% with obesity, 26% with diabetes), 132 (13%) had baseline cognitive impairment. Each SD higher waist circumference was associated with higher odds of cognitive impairment, odds ratio (OR) = 1.63; (95% confidence interval: 1.17, 2.24), with mediating pathways explaining 65% of the total effect (58% from diabetes; 7% from inflammation). At follow-up (mean 6.8 years), 106 of 535 (19.8%) had developed cognitive impairment. Each SD higher waist circumference was associated with higher odds of developing cognitive impairment (OR = 1.87; 95%CI: 1.18, 2.74); the direct effect of waist circumference explained 37% of the total effect and mediating pathways explained 63% (61% from diabetes; 2% from inflammation), although individual pathways were not statistically supported in the smaller sample. CONCLUSION: Diabetes, and to a lesser degree, adiposity-driven inflammation, appear to explain a substantial proportion of abdominal adiposity relationships with cognitive impairment. The impact of preventing and treating obesity on cognitive outcomes merits study.

Comparison of the DNA methylation profiles of human peripheral blood cells and transformed B-lymphocytes.

Epidemiological studies of DNA methylation (DNAm) profiles may hold substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Different cell types are likely to have different DNAm patterns. We investigate the DNAm differences between two types of biospecimens available in many genetic epidemiology studies. We compared DNAm patterns in two different DNA samples from each of 34 participants in the Genetic Epidemiology Network of Arteriopathy study (20 Caucasians and 14 African-Americans). One was extracted from peripheral blood cells (PBC) and the other from transformed B-lymphocytes (TBL). The genome-wide DNAm profiles were compared at over 27,000 genome-wide methylation sites. We found that 26 out of the 34 participants had correlation coefficients higher than 0.9 between methylation profiles of PBC and TBL. Although a high correlation was observed in the DNAm profile between PBC and TBL, we also observed variation across samples from different DNA resources and donors. Using principal component analysis of the DNAm profiles, the two sources of the DNA samples could be accurately predicted. We also identified 3,723 autosomal DNAm sites that had significantly different methylation statuses in PBC compared to TBL (Bonferroni corrected p value <0.05). Both PBC and TBL provide a rich resource for understanding the DNAm profiles in humans participating in epidemiologic studies. While the majority of DNAm findings in PBC and TBL may be consistent, caution must be used when interpreting results because of the possibility of cell type-specific methylation modification.

Health of Gullah families in South Carolina with type 2 diabetes: diabetes self-management analysis from project SuGar.

PURPOSE: The purpose of this study was to describe diabetes self-management practices and service utilization among Gullah families in South Carolina. METHODS: Data were obtained from 1276 persons with type 2 diabetes through interviews using the Family Health History Questionnaire. This was a primary analysis of a project conducted in conjunction with a parent study (Project SuGar) which focused on the molecular aspects of diabetes. Descriptive statistics were used for data analysis. RESULTS: Diabetes self-management behaviors were not consistent with recommendations from the American Diabetes Association. Over half (55.6%) reported exercising, but only 27.7% reported self-glucose monitoring. Service utilization was poor, less than half, (41.1%) reported referral to a diabetic class/diet, 32.8% reported making yearly visits to the ophthalmologist, 22.3% reported visiting the dentist, and only 12.8% reported visiting the podiatrist. CONCLUSIONS: Although some self-management behaviors were identified, Gullah family members remain at risk for preventable diabetes complications. Education must reflect behaviors and beliefs valued by Gullah individuals. Culturally appropriate educational programs may increase use of health care services aimed at decreasing preventable complications of type 2 diabetes in the Gullah population.

A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa.

PURPOSE: To characterize the course of retinal disease in X-linked progressive retinal atrophy 2 (XLPRA2), a canine model of early onset X-linked retinitis pigmentosa (XLRP) caused by a two-nucleotide microdeletion in RPGR ORF15. METHODS: The retinas of 25 XLPRA2-affected dogs (age range, 2-40.6 weeks) and age-matched control subjects were collected, fixed, and embedded in epoxy resin for morphologic evaluation or in optimal cutting temperature (OCT) medium for TUNEL assay and immunohistochemistry. Cell-specific antibodies were used to examine changes in rods and cones and to evaluate the effects of the primary photoreceptor degeneration on inner retinal cells. RESULTS: Abnormal development of photoreceptors was recognizable as early as 3.9 weeks of age. Outer segment (OS) misalignment was followed by their disorganization and fragmentation. Reduction in length and broadening of rod and cone inner segments (IS) was next observed, followed by the focal loss of rod and cone IS at later time points. The proportion of dying photoreceptors peaked at approximately 6 to 7 weeks of age and was significantly reduced after 12 weeks. In addition to rod and cone opsin mislocalization, there was early rod neurite sprouting, retraction of rod bipolar cell dendrites, and increased Müller cell reactivity. Later in the course of the disease, changes were also noted in horizontal cells and amacrine cells. CONCLUSIONS: XLPRA2 is an early-onset model of XLRP that is morphologically characterized by abnormal photoreceptor maturation followed by progressive rod-cone degeneration and early inner retina remodeling. The results suggest that therapeutic strategies for this retinal degeneration should target not solely photoreceptor cells but also inner retinal neurons.

Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators.

To improve the potency of 2-pralidoxime (2-PAM) for treating organophosphate poisoning, we dimerized 2-PAM and its analogs according to Wilson's pioneering work and the 3D structure of human acetylcholinesterase (hAChE) inactivated by isoflurophate. 1,7-Heptylene-bis-N,N'-syn-2-pyridiniumaldoxime, the most potent of the alkylene-linked dimeric reactivators, was readily synthesized using bistriflate and is 100 times more potent than 2-PAM in reactivating hAChE poisoned by isoflurophate. Experimental and computational studies confirm that 2-PAM in its biologically active form adopts the syn-I configuration. Further, they suggest that the improved performance of dimeric oximes is conferred by two-site binding with one oxime pointing toward the diisopropyl ester at the catalytic site of hAChE and the other anchored at the peripheral site. This type of binding may induce a conformational change in the acyl pocket loop which modulates the catalytic site via a domino effect.

From idea to graduation: the evolution of the first PhD program in a HBCU.

Hampton University has the distinction of being the first Historically Black College or University (HBCU) to fully implement a PhD in Nursing program. This was history making for our campus as the charter was changed to accommodate doctoral education. The PhD in Physics was the first doctoral program on campus, and Nursing was one of three doctoral programs that followed. Hampton University enrolled its first class of four students in the PhD in Nursing program in the fall of 1999. The major goal of the Hampton University PhD program in Nursing is the preparation of nurse scholars and researchers who can advance scientific knowledge and influence the development of effective health care policies and practices. This journey describes steps Hampton University has taken in addressing the demand for doctorally prepared nurses, especially minority nurses. Training more minority nurses impacts all communities, especially medically undeserved communities and minority populations.

Regional and cellular distribution of DREAM in adult rat brain consistent with multiple sensory processing roles.

We used immunohistochemistry to map the recently discovered EF-hand protein, DREAM (downstream regulatory element antagonist modulator), and compare its expression in rat brain with that of other key neural proteins. DREAM immunoreactivity was most intense in cerebellar granular cortex. That expression pattern matches one reported for Kv4.2, an interaction partner of DREAM in regulation of potassium channels. On the other hand, the regional and cellular expression of DREAM in cerebellum was opposite to that of calbindin D(28k). Other loci for DREAM expression included the hippocampus and retrosplenial granular cortex, which share afferent and efferent connections. A notable trend, however, was the consistent appearance of DREAM at primary sites for sensory processing. These included the optic tract, superior colliculus, olfactory bulb, and several thalamic relay centers such as the anterior dorsal, medial geniculate, dorsolateral geniculate, ventral posteromedial and ventral posterolateral nuclei. Altogether, the results are consistent with multiple functions for DREAM, including a potential role in transfer of sensory information.

Coping strategies of family members of hospitalized psychiatric patients.

This exploratory research paper investigated the coping strategies of families of hospitalized psychiatric patients and identified their positive and negative coping strategies. In this paper, the coping strategies of 45 family members were examined using a descriptive, correlational, mixed method research approach. Guided by the Neuman Systems Model and using the Family Crisis Oriented Personal Evaluation Scales and semistructured interviews, this paper found that these family members used more emotion-focused coping strategies than problem-focused coping strategies. The common coping strategies used by family members were communicating with immediate family, acceptance of their situation, passive appraisal, avoidance, and spirituality. The family members also utilized resources and support systems, such as their immediate families, mental health care professionals, and their churches.