Prevalence and risk factors for human immunodefiency virus and hepatitis C virus co-infection among drug users in innercity neighborhoods in Houston, Texas

Background. There are 200,000 HIV/HCV co-infected people in the US and IDUs are at highest risk of exposure. Between 52-92% of HIV infected IDUs are chronically infected with HCV. African Americans and Hispanics bear the largest burden of co-infections. Furthermore HIV/HCV co-infection is associated with high morbidity and mortality if not treated. The present study investigates the demographic, sexual and drug related risk factors for HIV/HCV co-infection among predominantly African American injecting and non-injecting drug users living in two innercity neighborhoods in Houston, Texas. ^ Methods. This secondary analysis used data collected between February 2004 and June 2005 from 1,889 drug users. Three case-comparison analyses were conducted to investigate the risk factors for HIV/HCV co-infection. HIV mono-infection, HCV mono-infection and non-infection were compared to HIV/HCV co-infection to build multivariate logistic regression models. Race/ethnicity and age were forced into each model regardless of significance in the univariate analysis. ^ Results. The overall prevalence of HIV/HCV co-infection was 3.9% while 39.8% of HIV infected drug users were co-infected with HCV and 10.7% of HCV infected drug users were co-infected with HIV. Among HIV infected IDUs the prevalence of HCV was 71.7% and among HIV infected NIDUs the prevalence of HCV was 24%. In the multivariate analysis, HIV/HCV co-infection was associated with injecting drug use when compared to HIV mono-infection, with MSM when compared to HCV mono-infection and with injecting drug use as well as MSM when compared to non-infection. ^ Conclusion. HIV/HCV co-infection was associated with a combination of sexual and risky injecting practices. More data on the prevalence and risk factors for co-infection among minority populations is urgently needed to support the development of targeted interventions and treatment options. Additionally there should be a focus on promoting safer sex and injecting practices among drug users as well as the expansion of routine testing for HIV and HCV infections in this high risk population.^

Follow-up care after a health fair screening in three Houston neighborhoods in 2008

Background. Each year thousands of people participate in mass health screenings for diabetes and hypertension, but little is known about whether or not those who receive higher than normal screening results obtain the recommended follow-up medical care, or what barriers they perceive to doing so. ^ Methods. Study participants were recruited from attendees at three health fairs in low-income neighborhoods in Houston, Texas Potential participants had higher than normal blood pressure (> 90/140 mgHg) or blood glucose readings (100 mm/dL fasting or 140 mm/dL random). Study participants were called at one, two, and three months and asked if they had obtained follow-up medical care; those who had not yet obtained follow-up care were asked to identify barriers. Using a modified Aday-Andersen model of health service access, the independent variables were individual and community characteristics and self-perceived need. The dependent variable was obtaining follow-up care, with barriers to care a secondary outcome. ^ Results. Eighty-two study participants completed the initial questionnaire and 59 participants completed the study protocol. Forty-eight participants (59% under an intent to treat analysis, 81% of those completing the study protocol) obtained follow-up care. Those who completed the initial questionnaire and who reported a regular source of care were significantly more likely to obtain follow-up care. For those who completed the study protocol the relationship between having a regular source of care and obtaining follow-up care approached but did not reach significance. For those who completed the initial questionnaire, self-described health status, when examined as a binary variable (good, very good, excellent, or poor, fair, not sure) was associated with obtaining follow-up care for those who rated their health as poor, fair, or not sure. While the group who completed the study protocol did not reach statistical significance, the same relationship between self-described health status of poor, fair, or not sure and obtaining follow-up care was present. The participants who completed the study protocol and described their blood pressure as OK or a little high were statistically more likely to get follow-up care than those who described it as high or very high. All those on oral medications for hypertension (12/12) and diabetes (4/4) who were told to obtain follow-up care did so; however, the small sample size allows this correlation to be of statistical significance only for those treating hypertension. ^ The variables significantly associated with obtaining follow-up care were having a regular source of care, self-described health status of poor, fair, or not sure, self-described blood pressure of OK or a little high, and taking medication for blood pressure. ^ At the follow-up telephone calls, 34 participants identified barriers to care; cost was a significant barrier reported by 16 participants, and 10 reported that they didn’t have time because they were working long hours after Hurricane Ike. ^ The study included the offer of access assistance: information about nearby safety-net providers, a visit to or information from the Health Information Center at their Neighborhood Center location, or information from Project Safety Net (a searchable web site for safety net providers). Access assistance was offered at the health fairs and then again at follow-up telephone calls to those who had not yet obtained follow-up care. Of the 48 participants who reported obtaining follow-up care, 26 said they had made use of the access assistance to do so. The use of access assistance was associated with being Hispanic, not having health insurance or a regular source of care, and speaking Spanish. It was also associated with being worried about blood glucose. ^ Conclusion. Access assistance, as a community enabling characteristic, may be useful in aiding low-income people in obtaining medical care. ^

Behavioral cognitions and factors related to hepatitis B vaccine acceptance and compliance in a cohort of drug users in Houston, Texas

Purpose. Drug users are a large group of those at highest risk for contracting Hepatitis B (HBV). This study sought to identify predictors of HBV vaccine acceptance and compliance in a cohort of current drug users in Houston, Texas. Perceived severity of HBV, perceived risk of HBV, perceived peer support of HBV vaccine, and perceived benefits of HBV vaccine were also examined assess their relationship to HBV compliance. ^ Methods. A randomized intervention study was conducted in a cohort of current drug users in Houston, Texas. Participants were recruited by community outreach workers from two urban neighborhoods in Houston known for high drug use. Participants were randomized to a standard vaccine schedule group or an accelerated vaccine schedule group. Participants were also randomized to either a standard behavioral intervention group or an enhanced behavioral intervention group designed to increase HBV vaccine acceptance and compliance. Baseline visits included an interview for demographic factors, drug and sexual behaviors, and HBV beliefs; and participants received the first dose of the HBV vaccine and one of the behavioral interventions. ^ Results. Of 1,643 screening participants, 77% accepted the HBV vaccine. Participants ages ≥50 were twice as likely to accept the vaccine. African Americans and less frequent drug users were also significantly more likely to accept the vaccine. Of the 1,259 participants who enrolled in the study, 75% were compliant to the HBV vaccine. Predictors of compliance were found to be race, housing status, and alcohol use. Speedball users were found to be 74% less likely to be compliant the HBV vaccine. None of the behavioral constructs assessed were found to significantly predict HBV compliance. However, additional analyses found that there were significant changes in mean scores of the behavioral concepts when measured at six month follow-up. ^ Conclusion. Results from this study indicate that when offered a free vaccine in the drug user community, a large percentage will be compliant to the vaccine series. The behavioral cognitions commonly used in HBV compliance research need to be extended to accurately fit this cohort. Also, vaccine intervention focus needs to be on reaching the homeless segment of the drug users and the speedball users. ^

The prevalence of periodontal disease in Mexican American vs European American elderly in three distinct socio-economic communities in San Antonio, Texas

Purpose of the Study: This study evaluated the prevalence of periodontal disease between Mexican American elderly and European American elderly residing in three socio-economically distinct neighborhoods in San Antonio, Texas. ^ Study Group: Subjects for the original protocol were participants of the Oral Health: San Antonio Longitudinal Study of Aging (OH: SALSA), which began with National Institutes of Health (NIH) funding in 1993 (M.J. Saunders, PI). The cohort in the study was the individuals who had been enrolled in Phases I and III of the San Antonio Heart Study (SAHS). This SAHS/SALSA sample is a community-based probability sample of Mexican American and European American residents from three socio-economically distinct San Antonio neighborhoods: low-income barrio, middle-income transitional, and upper-income suburban. The OH: SALSA cohort was established between July 1993 and May 1998 by sampling two subsets of the San Antonio Heart Study (SAHS) cohort. These subsets included the San Antonio Longitudinal Study of Aging (SALSA) cohort, comprised of the oldest members of the SAHS (age 65+ yrs. old), and a younger set of controls (age 35-64 yrs. old) sampled from the remainder of the SAHS cohort. ^ Methods: The study used simple descriptive statistics to describe the sociodemographic characteristics and periodontal disease indicators of the OH: SALSA participants. Means and standard deviations were used to summarize continuous measures. Proportions were used to summarize categorical measures. Simple m x n chi square statistics was used to compare ethnic differences. A multivariable ordered logit regression was used to estimate the prevalence of periodontal disease and test ethnic group and neighborhood differences in the prevalence of periodontal disease. A multivariable model adjustment for socio-economic status (income and education), gender, and age (treated as confounders) was applied. ^ Summary: In the unadjusted and adjusted model, Mexican American elderly demonstrated the greatest prevalence for periodontitis, p < 0.05. Mexican American elderly in barrio neighborhoods demonstrated the greatest prevalence for severe periodontitis, with unadjusted prevalence rates of 31.7%, 22.3%, and 22.4% for Mexican American elderly barrio, transitional, and suburban neighborhoods, respectively. Also, Mexican American elderly had adjusted prevalence rates of 29.4%, 23.7%, and 20.4% for barrio, transitional, and suburban neighborhoods, respectively. ^ Conclusion: This study indicates that the prevalence of periodontal disease is an important oral health issue among the Mexican American elderly. The results suggest that the socioeconomic status of the residential neighborhood increased the risk for severe periodontal disease among the Mexican American elderly when compared to European American elderly. A viable approach to recognizing oral health disparities in our growing population of Mexican American elderly is imperative for the provision of special care programs that will help increase the quality of care in this minority population.^

Design and analysis for three level hierarchical structures with count response

In numerous intervention studies and education field trials, random assignment to treatment occurs in clusters rather than at the level of observation. This departure of random assignment of units may be due to logistics, political feasibility, or ecological validity. Data within the same cluster or grouping are often correlated. Application of traditional regression techniques, which assume independence between observations, to clustered data produce consistent parameter estimates. However such estimators are often inefficient as compared to methods which incorporate the clustered nature of the data into the estimation procedure (Neuhaus 1993).1 Multilevel models, also known as random effects or random components models, can be used to account for the clustering of data by estimating higher level, or group, as well as lower level, or individual variation. Designing a study, in which the unit of observation is nested within higher level groupings, requires the determination of sample sizes at each level. This study investigates the design and analysis of various sampling strategies for a 3-level repeated measures design on the parameter estimates when the outcome variable of interest follows a Poisson distribution. ^ Results study suggest that second order PQL estimation produces the least biased estimates in the 3-level multilevel Poisson model followed by first order PQL and then second and first order MQL. The MQL estimates of both fixed and random parameters are generally satisfactory when the level 2 and level 3 variation is less than 0.10. However, as the higher level error variance increases, the MQL estimates become increasingly biased. If convergence of the estimation algorithm is not obtained by PQL procedure and higher level error variance is large, the estimates may be significantly biased. In this case bias correction techniques such as bootstrapping should be considered as an alternative procedure. For larger sample sizes, those structures with 20 or more units sampled at levels with normally distributed random errors produced more stable estimates with less sampling variance than structures with an increased number of level 1 units. For small sample sizes, sampling fewer units at the level with Poisson variation produces less sampling variation, however this criterion is no longer important when sample sizes are large. ^ 1Neuhaus J (1993). “Estimation efficiency and Tests of Covariate Effects with Clustered Binary Data”. Biometrics , 49, 989–996^

FUNCTIONS OF DEADENYLATION FACTORS IN MRNA DECAY AND MRNA PROCESSING BODY FORMATION

Most newly synthesized messenger RNAs possess a 5’ cap and a 3’ poly(A) tail. The process of poly(A) tail shortening, also termed deadenylation, is important for post-transcriptional gene regulation, because deadenylation not only leads to mRNA translational inhibition but also is the first step of major mRNA degradation. Translationally inhibited mRNAs can be stored and/or degraded in dynamic cytoplasmic foci termed mRNA processing bodies, or P bodies, which are conserved in eukaryotes. To shed new light on the mechanisms of P body formation and P body functions, I focused on the link between deadenylation factors and P bodies. I found that the two major deadenylation complexes, Pan3-Pan2 and Ccr4-Caf1, can both be enriched in P bodies. The deadenylase activity of the Ccr4-Caf1 complex is prerequisite for P body formation. Pan3, but not the deadenylase Pan2, is essential for P body formation. While the C-terminal domain of Pan3 is important for interaction with Pan2, Pan3 N-terminal domain is important for Pan3 to form cytoplasmic foci colocalizing with P bodies and to promote mRNA decay. Interestingly, Pan3 N-terminal domain may be phosphorylated to regulate Pan3 localization and functions. Aside from the functions of the two deadenylation complexes in P bodies, I also studied all reported human P body proteins as a whole using bioinformatics. This effort not only has generated a comprehensive picture of the functions of and interactions among human P body proteins, but also has predicted proteins that may regulate P body formation and/or functions. In summary, my study has established a direct link between mRNA deadenylation and P body formation and has also led to new hypotheses to guide future research on how P body dynamics are controlled.

Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian cells.

Deadenylation is the major step triggering mammalian mRNA decay. One consequence of deadenylation is the formation of nontranslatable messenger RNA (mRNA) protein complexes (messenger ribonucleoproteins [mRNPs]). Nontranslatable mRNPs may accumulate in P-bodies, which contain factors involved in translation repression, decapping, and 5'-to-3' degradation. We demonstrate that deadenylation is required for mammalian P-body formation and mRNA decay. We identify Pan2, Pan3, and Caf1 deadenylases as new P-body components and show that Pan3 helps recruit Pan2, Ccr4, and Caf1 to P-bodies. Pan3 knockdown causes a reduction of P-bodies and has differential effects on mRNA decay. Knocking down Caf1 or overexpressing a Caf1 catalytically inactive mutant impairs deadenylation and mRNA decay. P-bodies are not detected when deadenylation is blocked and are restored when the blockage is released. When deadenylation is impaired, P-body formation is not restorable, even when mRNAs exit the translating pool. These results support a dynamic interplay among deadenylation, mRNP remodeling, and P-body formation in selective decay of mammalian mRNA.

Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian cells.

Deadenylation is the major step triggering mammalian mRNA decay. One consequence of deadenylation is the formation of nontranslatable messenger RNA (mRNA) protein complexes (messenger ribonucleoproteins [mRNPs]). Nontranslatable mRNPs may accumulate in P-bodies, which contain factors involved in translation repression, decapping, and 5'-to-3' degradation. We demonstrate that deadenylation is required for mammalian P-body formation and mRNA decay. We identify Pan2, Pan3, and Caf1 deadenylases as new P-body components and show that Pan3 helps recruit Pan2, Ccr4, and Caf1 to P-bodies. Pan3 knockdown causes a reduction of P-bodies and has differential effects on mRNA decay. Knocking down Caf1 or overexpressing a Caf1 catalytically inactive mutant impairs deadenylation and mRNA decay. P-bodies are not detected when deadenylation is blocked and are restored when the blockage is released. When deadenylation is impaired, P-body formation is not restorable, even when mRNAs exit the translating pool. These results support a dynamic interplay among deadenylation, mRNP remodeling, and P-body formation in selective decay of mammalian mRNA.

The roles of UPF3a and UPF3b in nonsense mediated decay

Nonsense-mediated decay (NMD) degrades aberrant transcripts containing premature termination codons (PTCs). The T-cell receptor (TCR) locus undergoes error-prone rearrangements that frequently acquire PTCs. Transcripts harboring PTCs from this locus are downregulated much more than transcripts from non-rearranging genes. Efficient splicing is essential for this robust downregulation. ^ Here I show that TCR NMD is unique in another respect: it is not impaired by RNAi-mediated depletion of the NMD factor UPF3b. This differentiates TCR transcripts from classical NMD (assayed using β-globin or triose phosphate isomerase transcripts), which does depend on UPF3b. Depletion of UPF3a, which encodes a gene related to UPF3b, also had no effect on TCR NMD. Mapping experiments identified TCR sequences that when deleted or mutated caused a switch to UPF3b dependence. Since UPF3b dependence was invariably accompanied by less efficient RNA splicing, this suggests that UPF3b-dependent NMD occurs when transcripts are generated by inefficient splicing. Microarray analysis revealed the existence of many NMD-targeted mRNAs from wild-type genes whose downregulation is impervious to UPF3b depletion. This suggests the existence of an alternative NMD pathway independent of UPF3b that is widely used to downregulate the level of both normal and mutant transcripts. ^ During the course of my studies, I also found that the function of UPF3a is fundamentally distinct from that of UPF3b in several aspects. First, classical NMD failed to be impaired by UPF3a depletion, whereas it was reversed by UPF3b depletion. Second, UPF3a depletion had no effect on NMD elicited by tethered UPF2, whereas UPF3b depletion blocked this response. Thus, UPF3a does not function in classical NMD. Third, UPF3b depletion upregulated the expression of UPF3a, whereas UPF3a depletion had no effect on UPF3b expression. This suggests that a UPF3b-mediated feedback network exists that regulates the UPF3a expression. Lastly, UPF3a depletion but not UPF3b depletion significantly upregulated TCR precursor RNAs. This suggests that UPF3a, not UPF3b, functions in the surveillance of precursor RNAs, which typically contain many PTCs in the introns. Collectively, my data suggests that UPF3a and UPF3b are not functionally redundant, as previously thought, but instead have separable functions. ^

Has the development of a New Urbanist community affected the physical activity levels of residents in surrounding neighborhoods?

Study Aims. The neighborhood environment has been shown to influence physical activity levels, but little is known about how far-reaching these effects are. This study sought to determine whether or not the development of a New Urbanist community in Austin, Texas affected the physical activity levels of residents in surrounding neighborhoods. The results were stratified by demographic characteristics, residential distance from the New Urbanist community, and type of physical activity to determine if any observed changes varied by these factors.^ Methods. Self-report questionnaires were mailed to a random sample of households located within one mile of the New Urbanist development. The questionnaire included questions about physical activity behaviors before and after the community was constructed in 2006. Changes in reported levels of physical activity between the two time points were examined.^ Results. The prevalence and average minutes per week of total physical activity did not change. Significant increases in the frequency and quantity of moderate-intensity leisure-time physical activity were observed. The amount of time spent walking and biking for recreation outside of the neighborhood increased significantly among those living close to Mueller. The weekly time spent in vigorous-intensity activity increased significantly, especially among those living closer to Mueller. There were significant decreases in the prevalence of and time spent walking for transport. The use of Mueller parks and trails was highest among participants living close to Mueller.^ Conclusions. The nearby Mueller development does not appear to have encouraged sedentary members of the surrounding population to become physically active, but might be associated with increased weekly physical activity among those who were already active. The increase in vigorous-intensity physical activity and recreational walking/biking outside of the neighborhood among those subjects living closer to Mueller may be attributed to the use of Mueller parks and trails, which was also considerably higher among this group. People may be substituting the time they spent walking for transport before the Mueller development with moderate-intensity leisure-time physical activity. Future research should seek to identify barriers that may be preventing more nearby residents from using Mueller facilities for physical activity. ^

Walking Our Talk in the Neighborhoods: Building Professional/Natural Helper Partnerships

This article describes our efforts in Tacoma, Washington, to establish professional and natural helper partnerships to work with families involved in the child protective service system. It uses our experiences to describe the ways that natural helpers and professionals can help one another in getting better results for families.