Research and Publications - Department of Health Science

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Prevalence and Intensity of Infections of Ascaris lumbricoides and Trichuris trichiura and Associated Socio-demographic Variables in Four Rural Honduran Communities
(Fundação Oswaldo Cruz, 2001-04) Smith, H.M.; DeKaminsky, R.G.; Niwas, S.; Soto, R.J.; Jolly, P.E.
Between January and March 1998, a cross-sectional survey was carried out in four rural communi ties in Honduras, Central America. We examined the prevalence and intensity of Ascaris lumbricoides and Trichuris trichiura infections among 240 fecal specimens, and the association between selected socio-demographic variables and infection for 62 households. The overall prevalence of A. lumbricoides and T. trichiura was 45% (95% CI 39.0-51.9) and 38% (95% CI 31.8-44.4) respectively. The most intense infections for Ascaris and Trichuris were found in children aged 2-12 years old. By univariate analysis variables associated with infections of A. lumbricoides were: number of children 2-5 years old (p=0.001), level of formal education of respondents (p=0.01), reported site of defecation of children in households (p=0.02), households with children who had a recent history of diarrhea (p=0.002), and the location of households (p=0.03). Variables associated with both A. lumbricoides and T. trichiura infec tion included: number of children 6-14 years old (p=0.01, p=0.04, respectively), ownership of a latrine (p=0.04, p=0.03, respectively) and coinfection with either helminth (p=0.001, p=0.001, respectively). By multivariate analysis the number of children 2-5 years living in the household, (p=0.01, odds ratio (OR)=22.2), children with a recent history of diarrhea (p=0.0, OR=39.8), and infection of household members with T. trichiura (p=0.02, OR=16.0) were associated with A. lumbricoides infection. The number of children 6-14 years old in the household was associated with both A. lumbricoides and T. trichiura infection (p=0.04, p=0.01, OR=19.2, OR=5.2, respectively).
Effective media communication of disasters: Pressing problems and recommendations
(BMC, 2007) Lowrey, Wilson; Evans, Williams; Gower, Karla K.; Robinson, Jennifer A.; Ginter, Peter M.; McCormick, Lisa C.; Abdolrasulnia, Maziar; University of Alabama Birmingham; University of Alabama Tuscaloosa; University of Florida
Background: Public health officials and journalists play a crucial role in disseminating information regarding natural disasters, terrorism and other human-initiated disasters. However, research suggests that journalists are unprepared to cover terrorism and many types of natural disasters, in part because of lack sufficient expertise in science and medicine and training. The objective of this research was to identify solutions to problems facing journalists and public health public information officer (PIOs) of communicating with the public during natural and human-initiated disasters. Methods: To assist in identifying the most pressing problems regarding media response to health-related risks such as terrorism and large-scale natural disasters, 26 expert advisors were convened, including leaders representing journalists and public information officers, state health officials, experts in terrorism and emergency preparedness, and experts in health, risk, and science communication. The advisory group participated in prearranged interviews and were asked to identify and review bioterrorism educational resources provided to journalist. All advisory group members were then invited to attend a day long meeting January 29, 2004 to review the findings and reach consensus. Results: The most pressing problems were found to be a lack of coordination between PIO's and journalists, lack of resources for appropriately evaluating information and disseminating it efficiently, and a difference in perception of PIO's and journalist towards each others role during emergency situations. The advisory board developed a list of 15 recommendations that may enhance communication plans between PIO's, journalist and the public. The solutions were meant to be feasible in terms of costs and practical in terms of the professional and organizational realities in which journalists and PIO's work. Conclusion: It is clear that PIO's and journalists play crucial roles in shaping public response to terrorism and other disasters. The findings from this formative research suggest that perspectives and organizational processes often limit effective communication between these groups; though practical solutions such as participation of journalists in drills, scenario exercises, sharing of informational resources, and raising awareness at professional trade meetings may enhance the timely dissemination of accurate and appropriate information.
Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis
(BMC, 2010) Burgos, Paula I.; Causey, Zenoria L.; Tamhane, Ashutosh; Kelley, James M.; Brown, Elizabeth E.; Hughes, Laura B.; Danila, Maria I.; van Everdingen, Amalia; Conn, Doyt L.; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard D., Jr.; Moreland, Larry W.; van der Heijde, Desiree M.; Alarcon, Graciela S.; Bridges, S. Louis, Jr.; University of Alabama Tuscaloosa; Pontificia Universidad Catolica de Chile; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Emory University; University of North Carolina; University of North Carolina Chapel Hill; Medical University of South Carolina; Washington University (WUSTL)
Introduction: To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods: Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results: Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)(adj) = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions: We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations.
Aging Prisoners' Treatment Selection: Does Prospect Theory Enhance Understanding of End-of-Life Medical Decisions?
(Oxford University Press, 2011) Phillips, Laura L.; Allen, Rebecca S.; Harris, Grant M.; Presnell, Andrew H.; DeCoster, Jamie; Cavanaugh, Ronald; University of Alabama Tuscaloosa
Purpose: With the rapid growth in the older inmate population and the economic impact of end-of-life treatments within the cash-strapped prison system, consideration should be given to inmate treatment preferences. We examined end-of-life treatment preferences and days of desired life for several health scenarios among male inmates incarcerated primarily for murder. Design and Methods: Inmates over the age of 45 who passed a cognitive screening completed face-to-face interviews (N = 94; mean age = 57.7; SD = 10.68). Results: We found a 3-way interaction indicating that the effect of parole expectation on desire for life-sustaining treatment varied by race/ethnicity and treatment. Minority inmates desired cardiopulmonary resuscitation or feeding tubes only if they believed that they would be paroled. The model predicting desire for palliative care was not significant. Future days of desired life were related to prospective health condition, fear of death, negative affect, and trust in prison health care. Caucasian inmates expressed a desire for more days of life out of prison, whereas minority inmates did not differ in days of desired life either in or out of prison. Minorities wanted more days of life than Caucasians but only if they believed that they would be paroled. Implications: End-of-life care for the burgeoning inmate population is costly, and active life-sustaining treatments may not be desired under certain conditions. Specifically, expectation of parole but not current functional ability interacts with future illness condition in explaining inmates' desire for active treatment or days of desired life in the future.
A Qualitative Analysis of a Randomized Controlled Trial Comparing a Cognitive-Behavioral Treatment With Education
(Churchill Livingstone, 2011) Day, Melissa A.; Thorn, Beverly E.; Kapoor, Shweta; University of Alabama Tuscaloosa
Cognitive behavioral therapy (CBT) is a widely accepted psychosocial treatment for chronic pain. However, the efficacy of CBT has not been investigated within a rural setting. Furthermore, few studies have utilized first-person accounts to qualitatively investigate the key treatment elements and processes of change underlying the well-documented quantitative improvements associated with CBT. To address these gaps, we conducted a randomized controlled trial (RCT) investigating the efficacy of group CBT compared to an active education condition (EDU) within a rural, low-literacy population. Posttreatment semistructured interviews of 28 CBT and 24 EDU treatment completers were qualitatively analyzed. Emerging themes were collated to depict a set of finalized thematic maps to visually represent the patterns inherent in the data. Patterns were separated into procedural elements and presumed change processes of treatment. Key themes, subthemes, and example extracts for CBT and EDU are presented; unique and shared aspects pertaining to the thematic maps are discussed. Results indicate that while both groups benefited from the program, the CBT group described more breadth and depth of change as compared to the EDU group. Importantly, this study identified key treatment elements and explored possible processes of change from the patients' perspective. Perspective: This qualitative article describes patient-identified key procedural elements and change process factors associated with psychosocial approaches for chronic pain management. Results may guide further adaptations to existing treatment protocols for use within unique, under-served chronic pain populations. Continued development of patient-centered approaches may help reduce health, treatment, and ethnicity disparities. (C) 2011 by the American Pain Society
Sleep Disturbance and Risk Behaviors among Inner-City African-American Adolescents
(Springer, 2011) Umlauf, Mary Grace; Bolland, John M.; Lian, Brad E.; University of Alabama Tuscaloosa
Adolescents tend to experience more problems with sleep loss as a natural consequence of puberty, whereas teens from impoverished urban areas are likely to witness neighborhood violence and/or engage in risk behaviors that may affect sleep. Data from the Mobile Youth Survey, a longitudinal study of impoverished inner-city African-American adolescents (1998-2005; N = 20,716; age range = 9.75-19.25 years), were used to compare paired years of annual surveys elicited by questions about how sleep was affected when bad things happen to friends or family. Using a cross-lagged panel multivariate approach comparing reports for two sequential years and controlling for age/gender plus exposure to traumatic stress and violence, prior sleep disturbance was associated with carrying a knife/gun, brandishing a knife/gun, using a knife/gun, quick temperedness, warmth toward mother, worry, and belief in the neighborhood street code in the latter year. Conversely, seeing someone cut, stabbed, or shot, using alcohol, worry, and internalized anger were associated with sleep disturbance in a latter year. Although a limited measure of sleep disturbance was used, these findings support further research to examine sleep disturbance and risk behaviors among low-income adolescents.
A web-based diabetes intervention for physician: a cluster-randomized effectiveness trial
(Oxford University Press, 2011) Estrada, Carlos A.; Safford, Monika M.; Salanitro, Amanda H.; Houston, Thomas K.; Curry, William; Williams, Jessica H.; Ovalle, Fernando; Kim, Yongin; Foster, Pamela; Allison, Jeroan J.; US Department of Veterans Affairs; Veterans Health Administration (VHA); Veterans Affairs Medical Center - Birmingham; University of Alabama Birmingham; VA Tennessee Valley Healthcare System; Geriatric Research Education & Clinical Center; Vanderbilt University; University of Alabama Tuscaloosa; University of Massachusetts Worcester
To determine the effectiveness of a provider-based education and implementation intervention for improving diabetes control. Cluster-randomized trial with baseline and follow-up cross sections of diabetes patients in each participating physicians practice. Eleven US Southeastern states, 200608. Two hundred and five rural primary care physicians. Multi-component interactive intervention including Web-based continuing medical education, performance feedback and quality improvement tools. oAcceptable control' [hemoglobin A1c 9, blood pressure (BP) 140/90 mmHg, low-density lipoprotein cholesterol (LDL) 130 mg/dl] and ooptimal control' (A1c 7, BP 130/80 mmHg, LDL 100 mg/dl). Of 364 physicians attempting to register, 205 were randomized to the intervention (n 102) or control arms (n 103). Baseline and follow-up data were provided by 95 physicians (2127 patients). The proportion of patients with A1c 9 was similar at baseline and follow-up in both the control [adjusted odds ratio (AOR): 0.94; 95 confidence interval (CI): 0.61, 1.47] and intervention arms [AOR: 1.16 (95 CI: 0.80, 1.69)]; BP 140/90 mmHg and LDL 130 mg/dl were also similar at both measurement points (P 0.66, P 0.46; respectively). We observed no significant effect on diabetes control attributable to the intervention for any of the primary outcome measures. Intervention physicians engaged with the Website over a median of 64.7 weeks [interquartile range (IQR): 45.481.8) for a median total of 37 min (IQR: 1666). A wide-reach, low-intensity, Web-based interactive multi-component intervention did not improve control of glucose, BP or lipids for patients with diabetes of physicians practicing in the rural Southeastern US.
Randomized trial of group cognitive behavioral therapy compared with a pain education control for low-literacy rural people with chronic pain
(Lippincott Williams & Wilkins, 2011) Thorn, Beverly E.; Day, Melissa A.; Burns, John; Kuhajda, Melissa C.; Gaskins, Susan W.; Sweeney, Kelly; McConley, Regina; Ward, L. Charles; Cabbil, Chalanda; University of Alabama Tuscaloosa; Rush University
Chronic pain is a common and costly experience. Cognitive behavioral therapies (CBT) are efficacious for an array of chronic pain conditions. However, the literature is based primarily on urban (white) samples. It is unknown whether CBT works in low-socioeconomic status (SES) minority and nonminority groups. To address this question, we conducted a randomized controlled trial within a low-SES, rural chronic pain population. Specifically, we examined the feasibility, tolerability, acceptability, and efficacy of group CBT compared with a group education intervention (EDU). We hypothesized that although both interventions would elicit short-and long-term improvement across pain-related outcomes, the cognitively-focused CBT protocol would uniquely influence pain catastrophizing. Mixed design analyses of variance were conducted on the sample of eligible participants who did not commence treatment (N = 26), the intention-totreat sample (ITT; N = 83), and the completer sample (N = 61). Factors associated with treatment completion were examined. Results indicated significantly more drop-outs occurred in CBT. ITT analyses showed that participants in both conditions reported significant improvement across pain-related outcomes, and a nonsignificant trend was found for depressed mood to improve more in CBT than EDU. Results of the completer analyses produced a similar pattern of findings; however, CBT produced greater gains on cognitive and affect variables than EDU. Treatment gains were maintained at 6-month follow-up (N = 54). Clinical significance of the findings and the number of treatment responders is reported. Overall, these findings indicate that CBT and EDU are viable treatment options in low-SES minority and nonminority groups. Further research should target disseminating and sustaining psychosocial treatment options within underserved populations. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
Sleep duration change across breast cancer survivorship: associations with symptoms and health-related quality of life
(Springer, 2011) Alfano, Catherine M.; Lichstein, Kenneth L.; Vander Wal, Gregory S.; Smith, Ashley Wilder; Reeve, Bryce B.; McTiernan, Anne; Bernstein, Leslie; Baumgartner, Kathy B.; Ballard-Barbash, Rachel; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Alabama Tuscaloosa; University of North Carolina; University of North Carolina Chapel Hill; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; City of Hope; University of Louisville
Sleep duration among breast cancer survivors correlates with fatigue, depression, and health-related quality of life (HRQOL); however, this has not been studied longitudinally. This study investigated patterns of sleep duration change across the early breast cancer survivorship period, their demographic and clinical predictors, and their relationships with subsequent cancer-related symptoms and HRQOL. Breast cancer survivors (n = 572), were assessed 6 months post-diagnosis (current sleep & retrospective reports of pre-diagnosis sleep), 30 months post-diagnosis (sleep), and 39 months post-diagnosis (symptoms, HRQOL). Sleep duration change was determined by examining sleep at each time point in relation to published norms. Analysis of variance and logistic regression models tested demographic and clinical differences between the sleep change groups; linear regression models tested differences in symptoms and HRQOL. Half of the survivors reported no sleep duration change over time; however, 25% reported sleep changes indicating a temporary (5.6%), late-occurring (14%), or sustained (5.9%) change. Survivors reporting sustained or temporary sleep changes were more likely to have been treated with chemotherapy (OR = 2.62, P < 0.001) or gained weight after diagnosis (OR = 1.82, P = 0.04) than those with no sleep change. Sustained sleep changes were related to greater subsequent severity, affective, and sensory aspects of fatigue (beta s = 2.0, 2.3, 1.8; all P < 0.0001) and lower vitality (beta = -10.8, P = 0.005). Survivors treated with chemotherapy and those who gain weight after diagnosis may have increased risk for sustained sleep duration changes, which may increase their fatigue. These results point to the need for routine assessment of sleep as part of survivorship care.
Personality disorder features and insomnia status amongst hypnotic-dependent adults
(Elsevier, 2012) Ruiter, Megan E.; Lichstein, Kenneth L.; Nau, Sidney D.; Geyer, James D.; University of Alabama Birmingham; University of Alabama Tuscaloosa; University of Memphis
Objective: To determine the prevalence of personality disorders and their relation to insomnia parameters among persons with chronic insomnia with hypnotic dependence. Methods: Eighty-four adults with chronic insomnia with hypnotic dependence completed the SCID-II personality questionnaire, two-weeks of sleep diaries, polysomnography, and measures of insomnia severity, impact, fatigue severity, depression, anxiety, and quality of life. Frequencies, between-subjects t-tests and hierarchical regression models were conducted. Results: Cluster C personality disorders were most prevalent (50%). Obsessive-Compulsive personality disorder (OCPD) was most common (n = 39). These individuals compared to participants with no personality disorders did not differ in objective and subjective sleep parameters. Yet, they had poorer insomnia-related daytime functioning. OCPD and Avoidant personality disorders features were associated with poorer daytime functioning. OCPD features were related to greater fatigue severity, and overestimation of time awake was trending. Schizotypal and Schizoid features were positively associated with insomnia severity. Dependent personality disorder features were related to underestimating time awake. Conclusions: Cluster C personality disorders were highly prevalent in patients with chronic insomnia with hypnotic dependence. Features of Cluster C and A personality disorders were variously associated with poorer insomnia-related daytime functioning, fatigue, and estimation of nightly wake-time. Future interventions may need to address these personality features. (C) 2012 Elsevier B.V. All rights reserved.
Local Legal Infrastructure and Population Health
(American Public Health Association, 2012) Costich, Julia F.; Patton, Dana J.; University of Kentucky; University of Alabama Tuscaloosa
Objectives. We explored the association between the legal infrastructure of local public health, as expressed in the exercise of local fiscal and legislative authority, and local population health outcomes. Methods. Our unit of analysis was public health jurisdictions with at least 100 000 residents. The dependent variable was jurisdiction premature mortality rates obtained from the Mobilize Action Toward Community Health (MATCH) database. Our primary independent variables represented local public health's legal infrastructure: home rule status, board of health power, county government structure, and type of public health delivery system. Several control variables were included. We used a regression model to test the relationship between the varieties of local public health legal infrastructure identified and population health status. Results. The analyses suggested that public health legal infrastructure, particularly reformed county government, had a significant effect on population health status as a mediator of social determinants of health. Conclusions. Because states shape the legal infrastructure of local public health through power-sharing arrangements, our findings suggested recommendations for state legislation that positions local public health systems for optimal impact. Much more research is needed to elucidate the complex relationships among law, social capital, and population health status. (Am J Public Health. 2012;102:1936-1941. doi:10.2105/AJPH.2012.300656)
Identifying Activity Levels and Steps of People With Stroke Using a Novel Shoe-Based Sensor
(Lippincott Williams & Wilkins, 2012) Fulk, George D.; Edgar, S. Ryan; Bierwirth, Rebecca; Hart, Phil; Lopez-Meyer, Paulo; Sazonov, Edward; Clarkson University; University of Alabama Tuscaloosa
Background/Purpose: Advances in sensor technologies provide a method to accurately assess activity levels of people with stroke in their community. This information could be used to determine the effectiveness of rehabilitation interventions as well as provide behavior-enhancing feedback. The purpose of this study was to assess the accuracy of a novel shoe-based sensor system (SmartShoe) to identify different functional postures and steps in people with stroke. The SmartShoe system consists of five force-sensitive resistors built into a flexible insole and an accelerometer on the back of the shoe. Pressure and acceleration data are sent via Bluetooth to a smart phone. Methods: Participants with stroke wore the SmartShoe while they performed activities of daily living (ADLs) in sitting, standing, and walking positions. Data from four participants were used to develop a multilayer perceptron artificial neural network (ANN) to identify sitting, standing, and walking. A signal-processing algorithm used data from the pressure sensors to estimate the number of steps taken while walking. The accuracy, precision, and recall of the ANN for identifying the three functional postures were calculated with data from a different set of participants. Agreement between steps identified by SmartShoe and actual steps taken was analyzed by the Bland Altman method. Results: The SmartShoewas able to accurately identify sitting, standing, and walking. Accuracy, precision, and recall were all greater than 95%. The mean difference between steps identified by SmartShoe and actual steps was less than one step. Discussion: The SmartShoe was able to accurately identify different functional postures, using a unique combination of pressure and acceleration data, of people with stroke as they performed different ADLs. There was a strong level of agreement between actual steps taken and steps identified by the SmartShoe. Further study is needed to determine whether the SmartShoe could be used to provide valid information on activity levels of people with stroke while they go about their daily lives in their home and community.
Predictors of Primary Care Physicians' Self-reported Intention to Conduct Suicide Risk Assessments
(Springer, 2012) Hooper, Lisa M.; Epstein, Steven A.; Weinfurt, Kevin P.; DeCoster, Jamie; Qu, Lixin; Hannah, Natalie J.; University of Alabama Tuscaloosa; Georgetown University; Duke University; University of Virginia
Primary care physicians play a significant role in depression care, suicide assessment, and suicide prevention. However, little is known about what factors relate to and predict quality of depression care (assessment, diagnosis, and treatment), including suicide assessment. The authors explored the extent to which select patient and physician factors increase the probability of one element of quality of care: namely, intention to conduct suicide assessment. Data were collected from 404 randomly selected primary care physicians after their interaction with CD-ROM vignettes of actors portraying major depression with moderate levels of severity. The authors examined which patient factors and physician factors increase the likelihood of physicians' intention to conduct a suicide assessment. Data from the study revealed that physician-participants inquired about suicide 36% of the time. A random effects logistic model indicated that several factors were predictive of physicians' intention to conduct a suicide assessment: patient's comorbidity status (odds ratio (OR)=0.61; 95% confidence interval (CI)=0.3701.00), physicians' age (OR=0.67; 95% CI=0.4900.92), physicians' race (OR=1.84; 95% CI=1.0803.13), and how depressed the physician perceived the virtual patient to be (OR=0.58; 95% CI=0.3900.87). A substantial number of primary care physicians in this study indicated they would not assess for suicide, even though most physicians perceived the virtual patient to be depressed or very depressed. Further study is needed to establish factors that may be modified and targeted to increase the likelihood of physicians' providing one element of quality of care-suicide assessment-for depressed patients.
Exposure to Green Tea Extract Alters the Incidence of Specific Cyclophosphamide-Induced Malformations
(Wiley, 2012) Logsdon, Amanda L.; Herring, Betty J.; Lockard, Jarrett E.; Miller, Brittany M.; Kim, Hanna; Hood, Ronald D.; Bailey, Melissa M.; University of Alabama Tuscaloosa
BACKGROUND Green tea extract (GTE) has been shown to have antioxidative properties due to its high content of polyphenols and catechin gallates. Previous studies indicated that catechin gallates scavenge free radicals and attenuate the effects of reactive oxygen species. Cyclophosphamide (CP) produces reactive oxidative species, which can have adverse effects on development, causing limb, digit, and cranial abnormalities. The current study was performed to determine if exposure to GTE can decrease teratogenic effects induced by CP in CD-1 mice. METHODS From gestation days (GD) 613, mated CD-1 mice were dosed with 400 or 800 mg/kg/d GTE; 100, 200, 400, or 800 mg/kg/d GTE + CP; CP alone, or the vehicle. GTE was given by gavage. CP (20 mg/kg) was given by intraperitoneal injection on GD 10. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS The highest GTE dose did not effectively attenuate, and in some cases exacerbated the negative effect of CP. GTE alone was also associated with an increased incidence of microblepharia. Conversely, moderate GTE doses (200 and/or 400 mg/kg/d) attenuated the effect of CP on fetal weight and (GTE 200 mg/kg/d) decreased the incidences of certain defects resulting from CP exposure. CONCLUSIONS Exposure of a developing mammal to moderate doses of GTE can modulate the effects of exposure to CP during development, possibly by affecting biotransformation, while a higher GTE dose tended to exacerbate the developmental toxicity of CP. GTE alone appeared to cause an adverse effect on eyelid development. Birth Defects Res (Part B) 95:195-201, 2012. (C) 2012 Wiley Periodicals, Inc.
The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds
(Hindawi, 2012) Inamdar, Arati A.; Chaudhuri, Anathbandhu; O'Donnell, Janis; University of Alabama Tuscaloosa; Rutgers State University New Brunswick; University of Nebraska Medical Center
Epidemiological studies link the herbicide paraquat to increased incidence of Parkinson's disease (PD). We previously reported that Drosophila exposed to paraquat recapitulate PD symptoms, including region-specific degeneration of dopaminergic neurons. Minocycline, a tetracycline derivative, exerts ameliorative effects in neurodegenerative disease models, including Drosophila. We investigated whether our environmental toxin-based PD model could contribute to an understanding of cellular and genetic mechanisms of minocycline action and whether we could assess potential interference with these drug effects in altered genetic backgrounds. Cofeeding of minocycline with paraquat prolonged survival, rescued mobility defects, blocked generation of reactive oxygen species, and extended dopaminergic neuron survival, as has been reported previously for a genetic model of PD in Drosophila. We then extended this study to identify potential interactions of minocycline with genes regulating dopamine homeostasis that might modify protection against paraquat and found that deficits in GTP cyclohydrolase adversely affect minocycline rescue. We further performed genetic studies to identify signaling pathways that are necessary for minocycline protection against paraquat toxicity and found that mutations in the Drosophila genes that encode c-Jun N-terminal kinase (JNK) and Akt/Protein kinase B block minocycline rescue.
Functional Analysis of VPS41-Mediated Neuroprotection in Caenorhabditis elegans and Mammalian Models of Parkinson's Disease
(Society for Neuroscience, 2012) Harrington, Adam J.; Yacoubian, Talene A.; Slone, Sunny R.; Caldwell, Kim A.; Caldwell, Guy A.; University of Alabama Tuscaloosa; University of Alabama Birmingham
Disruption of the lysosomal system has emerged as a key cellular pathway in the neurotoxicity of alpha-synuclein (alpha-syn) and the progression of Parkinson's disease (PD). A large-scale RNA interference (RNAi) screen using Caenorhabditis elegans identified VPS-41, a multidomain protein involved in lysosomal protein trafficking, as a modifier of alpha-syn accumulation and dopaminergic neuron degeneration (Hamamichi et al., 2008). Previous studies have shown a conserved neuroprotective function of human VPS41 (hVPS41) against PD-relevant toxins in mammalian cells and C. elegans neurons (Ruan et al., 2010). Here, we report that both the AP-3 (heterotetrameric adaptor protein complex) interaction domain and clathrin heavy-chain repeat domain are required for protecting C. elegans dopaminergic neurons from alpha-syn-induced neurodegeneration, as well as to prevent alpha-syn inclusion formation in an H4 human neuroglioma cell model. Using mutant C. elegans and neuron-specific RNAi, we revealed that hVPS41 requires both a functional AP-3 (heterotetrameric adaptor protein complex) and HOPS (homotypic fusion and vacuole protein sorting)-tethering complex to elicit neuroprotection. Interestingly, two nonsynonymous single-nucleotide polymorphisms found within the AP-3 interacting domain of hVPS41 attenuated the neuroprotective property, suggestive of putative susceptibility factors for PD. Furthermore, we observed a decrease in alpha-syn protein level when hVPS41 was overexpressed in human neuroglioma cells. Thus, the neuroprotective capacity of hVPS41 may be a consequence of enhanced clearance of misfolded and aggregated proteins, including toxic alpha-syn species. These data reveal the importance of lysosomal trafficking in maintaining cellular homeostasis in the presence of enhanced alpha-syn expression and toxicity. Our results support hVPS41 as a potential novel therapeutic target for the treatment of synucleinopathies like PD.
Health Disparities Grants Funded by National Institute on Aging: Trends Between 2000 and 2010
(Oxford University Press, 2012) Kim, Giyeon; DeCoster, Jamie; Huang, Chao-Hui; Parmelee, Patricia; University of Alabama Tuscaloosa; University of Virginia
Purpose of the Study: The present study examined the characteristics of health disparities grants funded by National Institute on Aging (NIA) from 2000 to 2010. Objectives were (a) to examine longitudinal trends in health disparities-related grants funded by NIA and (b) to identify moderators of these trends. Design and Methods: Our primary data source was the National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) system. The RePORTER data were merged with data from the Carnegie Classification of Institutions of Higher Education. General linear models were used to examine the longitudinal trends and how these trends were associated with type of grant and institutional characteristics. Results: NIA funded 825 grants on health disparities between 2000 and 2010, expending approximately 330 million dollars. There was an overall linear increase over time in both the total number of grants and amount of funding, with an outlying spike during 2009. These trends were significantly influenced by several moderators including funding mechanism and type of institution. Implications: The findings highlight NIA's current efforts to fund health disparities grants to reduce disparities among older adults. Gerontology researchers may find this information very useful for their future grant submissions.
Report from the First Snake Genomics and Integrative Biology Meeting
(Genomic Standards Consortium, 2012) Castoe, Todd A.; Braun, Edward L.; Bronikowski, Anne M.; Cox, Christian L.; Rabosky, Alison R. Davis; de Koning, A. P. Jason; Dobry, Jason; Fujita, Matthew K.; Giorgianni, Matt W.; Hargreaves, Adam; Henkel, Christiaan V.; Mackessy, Stephen P.; O'Meally, Denis; Rokyta, Darin R.; Secor, Stephen M.; Streicher, Jeffrey W.; Wray, Kenneth P.; Yokoyama, Ken D.; Pollock, David D.; University of Colorado Anschutz Medical Campus; University of Florida; Iowa State University; University of Texas Arlington; University of California Berkeley; Harvard University; University of Wisconsin Madison; Bangor University; Leiden University - Excl LUMC; Leiden University; University of Northern Colorado; University of Canberra; Florida State University; University of Alabama Tuscaloosa
This report summarizes the proceedings of the 1st Snake Genomics and Integrative Biology Meeting held in Vail, CO USA, 5-8 October 2011. The meeting had over twenty registered participants, and was conducted as a single session of presentations. Goals of the meeting included coordination of genomic data collection and fostering collaborative interactions among researchers using snakes as model systems.
Variation in the Corticotropin-Releasing Hormone Receptor 1 (CRHR1) Gene Influences fMRI Signal Responses during Emotional Stimulus Processing
(Society for Neuroscience, 2012) Hsu, David T.; Mickey, Brian J.; Langenecker, Scott A.; Heitzeg, Mary M.; Love, Tiffany M.; Wang, Heng; Kennedy, Susan E.; Pecina, Marta; Shafir, Tal; Hodgkinson, Colin A.; Enoch, Mary-Anne; Goldman, David; Zubieta, Jon-Kar; University of Michigan; University of Alabama Tuscaloosa; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA)
The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1 (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability. The present study explores whether those observations extend to the neuronal processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and a preliminary sample of 16 unmedicated patients with MDD who completed a functional magnetic resonance imaging scan while viewing blocks of positive, negative, and neutral words. In addition, potential mediating factors such as early life stress, sex, personality traits, and negative memory bias were examined. Robust differences in blood oxygenation level-dependent (BOLD) signal were found in healthy controls (A allele carriers > GG-homozygotes) in the right middle temporal/angular gyrus while subjects were viewing negative versus neutral words. Among GG-homozygotes, BOLD signal in the subgenual cingulate was greater in MDD participants (n = 9) compared with controls (n = 33). Conversely, among A-carriers, BOLD signal was smaller in MDD (n = 7) compared with controls (n = 50) in the hypothalamus, bilateral amygdala, and left nucleus accumbens. Early life stress, personality traits, and levels of negative memory bias were associated with brain activity depending on genotype. Results from healthy controls and a preliminary sample of MDD participants show that CRHR1 single nucleotide polymorphism rs110402 moderates neural responses to emotional stimuli, suggesting a potential mechanism of vulnerability for the development of MDD.
Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group
(American Society of Clinical Oncology, 2012) Ebb, David; Meyers, Paul; Grier, Holcombe; Bernstein, Mark; Gorlick, Richard; Lipshultz, Steven E.; Krailo, Mark; Devidas, Meenakshi; Barkauskas, Donald A.; Siegal, Gene P.; Ferguson, William Shay; Letson, George Douglas; Marcus, Karen; Goorin, Allen; Beardsley, Peter; Marina, Neyssa; Harvard University; Massachusetts General Hospital; Dana-Farber Cancer Institute; Memorial Sloan Kettering Cancer Center; Montefiore Medical Center; University of Miami; Children's Oncology Group (COG); University of South Florida; H Lee Moffitt Cancer Center & Research Institute; University of Southern California; Lucile Packard Children's Hospital (LPCH); Stanford University; University of Alabama Tuscaloosa; Saint Louis University; Yale University; Dalhousie University
Purpose Despite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression. Patients and Methods Among 96 evaluable patients with newly diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by immunohistochemistry. All patients received chemotherapy with cisplatin, doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was administered with doxorubicin to minimize the risk of cardiotoxicity from treatment with trastuzumab and anthracycline. Only patients with HER2 overexpression received concurrent therapy with trastuzumab given for 34 consecutive weeks. Results The 30-month event-free and overall survival rates for patients with HER2 overexpression treated with chemotherapy and trastuzumab were 32% and 59%, respectively. For patients without HER2 overexpression, treated with chemotherapy alone, the 30-month event-free and overall survival rates were 32% and 50%, respectively. There was no clinically significant short-term cardiotoxicity in patients treated with trastuzumab and doxorubicin. Conclusion Despite intensive chemotherapy plus trastuzumab for patients with HER2-positive disease, the outcome for all patients was poor, with no significant difference between the HER2-positive and HER2-negative groups. Although our findings suggest that trastuzumab can be safely delivered in combination with anthracycline-based chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain. Definitive assessment of trastuzumab's potential role in treating osteosarcoma would require a randomized study of patients with HER2-positive disease.

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