Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins.

cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture.

Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins.

cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture.

The care to share HIV disclosure study - the attitudes toward and beliefs about HIV disclosure among perinatally-infected HIV-positive youth and their caregivers

HIV incidence has not changed since the introduction of the pandemic. Daily 14,000 persons are infected with HIV and 25 to 50% of the HIV-infected population and subgroups respectively are estimated to be unaware of their HIV diagnosis. Perinatally-infected HIV-positive youth, aged 13-24 years, have survived unexpectedly into adulthood, have had unique HIV disclosure experiences and now face HIV disclosure issues of adulthood and perhaps parenthood. Despite new effective HIV therapies, no HIV prevention plan exists that has diminished the rate of new HIV infections. HIV stigma and lack of universal HIV reporting laws dissuade timely HIV disclosure. Missed HIV disclosure perpetuates HIV transmission and infection. Understanding the attitudes and beliefs of HIV disclosure among perinatally-infected HIV-positive youth and their caregivers may uncover reasons to HIV disclosure delays, avoidance and intentions. The Care to Share HIV Disclosure study was designed to identify the attitudes and beliefs of HIV disclosure among HIV-positve youth (aged 13-24 years), who were infected from birth and who knew their HIV diagnosis, along with their caregivers. Twenty-six participants (15 youth and 11 caregivers) completed the theory-based questionnaires of a 21-item multiple choice survey on HIV disclosure framed in the Theory of Reasoned Action and Theory of Planned Behavior and included an additional open-ended survey that applied the Transactional Model of Stress and Coping to address youth's and caregivers' HIV disclosure experiences. Youth were found to have a selective unfavorable HIV disclosure outcome when among referents of close friends. However youth did believe in HIV partner notification. For caregivers, it mattered who disclosed the HIV illness to the youth. HIV stigma was of concern based on the youths' tendency to believe in keeping HIV a secret and their caregivers' ambivalence to HIV secrecy. However, favorable HIV disclosure outcomes were identified for both youth and caregivers the potential for HIV disclosure: when seeking HIV knowledge, when around caregivers and close family and in situations of perceived controllability as when helping others learn about HIV. These findings unveil HIV disclosure attitudes and beliefs within this population and may reveal the attributes that may inhibit or promote HIV disclosure behaviors. HIV disclosure studies that address attitudes and beliefs among larger populations of youth and HIV-infected persons are necessary to identify effective individual, group and society approaches that would promote timely, responsible and meaningful HIV disclosure methods that promote a healthy identity and interrupt HIV transmission.^

A systematic review of literature to compare the fertility desires among HIV positive women and cancer survivors

Background. Decision-making on reproductive issues is influenced by an interplay of individual, familial, medical, religious and socio-cultural factors. Women with chronic medical illnesses such an HIV infection and cancers are often fraught with decisional conflicts about child-bearing. With increase in the incidence of these illnesses as well as improvement in survival rates, there is a need to pay due attention to the issue of reproductive decision-making. Examining the prevalence and determinants of fertility desires in the two groups in a comparative manner would help bring to light perception of the medical community and the society in general on the two illnesses and the issue of motherhood. ^ Methods. Systematic literature search was undertaken using databases such as MEDLINE (PubMED), MEDLINE (Ovid), PsycInfo and Web of Science. Articles published in English and English language abstracts for foreign articles were included. Studies that explore ‘fertility desires’ as the outcome variable were included. Quantitative studies which have assessed the prevalence of fertility desires as well as qualitative studies which have provided a descriptive understanding of factors governing reproductive desires were included in the review. ^ Results. A total of 34 articles (29 studies examining HIV and 5 studies examining cancer in relation to fertility desires). Variables such as age, stage of illness, support of spouse and family, perception of the medical community and one’s own view of motherhood were key determinants among both groups. ^ Conclusion. There is a need for uniform, systematic research in this field. It is important that health care workers acknowledge these decisional conflicts, include them as part of the medical care of these patients and provide guidance with the right balance of information, practicality and compassion.^

Subjective well -being as predictor of mortality, heart disease, and obesity: Prospective evidence from the Alameda County Study

Based on the World Health Organization's (1965) definition of health, understanding of health requires understanding of positive psychological states. Subjective Well-being (SWB) is a major indicator of positive psychological states. Up to date, most studies of SWB have been focused on its distributions and determinants. However, study of its consequences, especially health consequences, is lacking. This dissertation research examined Subjective Well-being, as operationally defined by constructs drawn from the framework of Positive Psychology, and its sub-scores (Positive Feelings and Negative Feelings) as predictors of three major health outcomes—mortality, heart disease, and obesity. The research used prospective data from the Alameda County Study over 29 years (1965–1994), based on a stratified, randomized, representative sample of the general public in Alameda County, California (Baseline N = 6928). ^ Multivariate analyses (Survival analyses using sequential Cox Proportional Hazard models in the cases of mortality and heart disease, and sequential Logistic Regression analyses in the case of obesity) were performed as the main methods to evaluate the associations of the predictors and the health outcomes. The results revealed that SWB reduced risks of all-cause mortality, natural-cause mortality, and cardiovascular mortality. Positive feelings not only had an even stronger protective effect against all-cause, natural-cause and cardiovascular mortality, but also predicted decreased unnatural-cause mortality which includes deaths from suicide, homicide, accidents, mental disorders, drug dependency, as well as alcohol-related liver diseases. These effects were significant even after adjusted for age, gender, education, and various physical health measures, and, in the case of cardiovascular mortality, obesity and health practices (alcohol consumption, smoking, and physical activities). However, these two positive psychological indicators, SWB and positive feelings, did not predict obesity. And negative feelings had no significant effect on any of the health outcomes evaluated, i.e., all-cause mortality, natural- and unnatural-cause mortality, cardiovascular mortality, or obesity, after covariates were controlled. These findings were discussed (1) in comparison with relevant existing studies, (2) in terms of their implications in health research and promotion, (3) in terms of the independence of positive and negative feelings, and (4) from a Positive Psychology perspective and its significance in Public Health research and practice. ^

The diagnostic value of a 12-lead electrocardiogram in patients with cardiac tamponade due to a malignant pericardial effusion

Background. Cardiac tamponade can occur when a large amount of fluid, gas, singly or in combination, accumulating within the pericardium, compresses the heart causing circulatory compromise. Although previous investigators have found the 12-lead ECG to have a poor predictive value in diagnosing cardiac tamponade, very few studies have evaluated it as a follow up tool for ruling in or ruling out tamponade in patients with previously diagnosed malignant pericardial effusions. ^ Methods. 127 patients with malignant pericardial effusions at the MD Anderson Cancer Center were included in this retrospective study. While 83 of these patients had a cardiac tamponade diagnosed by echocardiographic criteria (Gold standard), 44 did not. We computed the sensitivity (Se), specificity (Sp), positive (PPV) and negative predictive values (NPV) for individual and combinations of ECG abnormalities. Individual ECG abnormalities were also entered singly into a univariate logistic regression model to predict tamponade. ^ Results. For patients with effusions of all sizes, electrical alternans had a Se, Sp, PPV and NPV of 22.61%, 97.61%, 95% and 39.25% respectively. These parameters for low voltage complexes were 55.95%, 74.44%, 81.03%, 46.37% respectively. The presence of all three ECG abnormalities had a Se = 8.33%, Sp = 100%, PPV = 100% and NPV = 35.83% while the presence of at least one of the three ECG abnormalities had a Se = 89.28%, Sp = 46.51%, PPV = 76.53%, NPV = 68.96%. For patients with effusions of all sizes electrical alternans had an OR of 12.28 (1.58–95.17, p = 0.016), while the presence of at least one ECG abnormality had an OR of 7.25 (2.9–18.1, p = 0.000) in predicting tamponade. ^ Conclusions. Although individual ECG abnormalities had low sensitivities, specificities, NPVs and PPVs with the exception of electrical alternans, the presence of at least one of the three ECG abnormalities had a high sensitivity in diagnosing cardiac tamponade. This could point to its potential use as a screening test with a correspondingly high NPV to rule out a diagnosis of tamponade in patients with malignant pericardial effusions. This could save expensive echocardiographic assessments in patients with previously diagnosed pericardial effusions. ^

Educational Technology-Benefits and Barriers

Statement of Problem: The second background paper for the Medical School Objective Project (MSOP), defined Educational Technology (ET) as the use of information technology to facilitate student’s learning.1 Medical schools as a group have made limited progress in accomplishing the recommended educational technology goals and there had been much greater use of such technology in basic sciences courses than in clinical clerkships. We will explore the positive and negative implications of incorporating ET into the educational experience of TMC schools. [See PDF for complete abstract]

First Trimester Screening and its Impact on Uptake of Diagnostic Testing

Introduction: First Trimester Screening (FTS) combines maternal age with fetal nuchal translucency (NT) and maternal analytes to identify pregnancies at an increased risk for Down syndrome and trisomy 18. Though the accuracy of this screening is high, it cannot replace the conclusive accuracy of prenatal diagnostic testing (PDT). Since FTS has been available, a decrease in the number of women who pursue PDT has been observed. This study sought to determine if there has been a significant change in the amount of PDT performed in our clinics, if the type of FTS result affects the patient’s decision regarding PDT, and what the patient’s intentions are regarding PDT. Material and Methods: A database review was performed for the two years prior and the two years after the January 2007 American College of Obstetricians and Gynecologists (ACOG) guidelines regarding FTS were issued. We compared the number of women who were AMA and the number of women who were AMA and had PDT between those time periods. We also determined the number of positive and negative FTS results, and determined how many of those patients had PDT. Finally, we surveyed our patients and referring physicians to determine: what the patient understands about FTS, what the patient’s intentions are regarding FTS, and how physicians present the option of FTS to their patients. Results: We determined that there was a 19.6% decrease in the amount of PDT performed when we compared the two time periods at our three specified clinics. Many of our patients were against having PDT prior to their genetic counseling session, but after they received genetic counseling, 76% of our population became open to the possibility of having PDT. Conclusion: Similar to previous studies, we determined that there has been a significant decrease in the number of PDT procedures performed at our clinics, which coincides with the release of the January 2007 ACOG statement regarding FTS. While our patients regarded FTS as a way to gain early information about their pregnancy in a non-invasive manner, they also stated they would use their results as a way to aid in their decision regarding PDT.

The performance of human papillomavirus high-risk DNA testing in the screening and diagnostic settings.

OBJECTIVE: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older. MATERIALS AND METHODS: Screening (n=835) and diagnosis (n=518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear. RESULTS: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR- were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR- were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing. CONCLUSIONS: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older.

Comparison of OG1RF and an isogenic fsrB deletion mutant by transcriptional analysis: the Fsr system of Enterococcus faecalis is more than the activator of gelatinase and serine protease.

The FsrABC system of Enterococcus faecalis controls the expression of gelatinase and a serine protease via a quorum-sensing mechanism, and recent studies suggest that the Fsr system may also regulate other genes important for virulence. To investigate the possibility that Fsr influences the expression of additional genes, we used transcriptional profiling, with microarrays based on the E. faecalis strain V583 sequence, to compare the E. faecalis strain OG1RF with its isogenic mutant, TX5266, an fsrB deletion mutant. We found that the presence of an intact fsrB influences expression of numerous genes throughout the growth phases tested, namely, late log to early stationary phase. In addition, the Fsr regulon is independent of the activity of the proteases, GelE and SprE, whose expression was confirmed to be activated at all three time points tested. While expression of some genes (i.e., ef1097 and ef0750 to -757, encoding hypothetical proteins) was activated in late log phase in OG1RF versus the fsrB deletion mutant, expression of ef1617 to -1634 (eut-pdu orthologues) was highly repressed by the presence of an intact Fsr at entry into stationary phase. This is the first time that Fsr has been characterized as a negative regulator. The newly recognized Fsr-regulated targets include other factors, besides gelatinase, described as important for biofilms (BopD), and genes predicted to encode the surface proteins EF0750 to -0757 and EF1097, along with proteins implicated in several metabolic pathways, indicating that the FsrABC system may be an important regulator in strain OG1RF, with both positive and negative effects.

Integrins in human T cell function: Transdominant regulation, conformational constraints, and intracellular effectors

Integrin adhesion molecules have both positive and negative potential in the regulation of peripheral blood T cell (PB T cell) activation, yet their mechanism of action in the mediation of human T lymphocyte function remains largely undefined. The goals of this study then were to elucidate integrin signaling mechanisms in PB T cells.^ By ligating $\beta$1 integrins with mAb 18D3, it was demonstrated that costimulation of PB T cell proliferation induced by coimmobilizing antibodies specific for $\beta$1, $\beta$2, and $\beta$7 integrin subfamilies in conjunction with the anti-CD3 mAb OKT3 was inhibited. Costimulation of T cell proliferation induced by non-integrins CD4, CD26, CD28, CD44, CD45RA, or CD45RO was unaffected. Inhibition of costimulation correlated with diminished IL-2 production. In his manner, $\beta$1 integrins could regulate heterologous integrins of the $\beta$2 and $\beta$7 subfamilies in a transdominant fashion. It was also demonstrated that integrin costimulation of T cell activation was acutely sensitive to the structural conformation of $\beta$1 integrins. Using the cyclic hexapeptide CWLDVC (TBC772, which is based on the $\alpha4\beta1$ integrin binding site in fibronectin) in soluble form, it was shown that integrins locked into a conformation displaying a neo-epitope called the ligand induced binding site (LIBS) recognized by mAb 15/7 were inhibited from sending mitogenic signals to T cells. When BSA-conjugated TBC772 was coimmobilized with anti-CD3 mAb OKT3, costimulation of proliferation occurred. This suggested that temporally uncoupling integrin receptor occupancy from receptor crosslinking inhibited $\beta$1 integrin signaling mechanisms. When subsets of PB T cells were examined to determine those initially activated by integrins within 6 hours of activation, costimulation induced intracellular accumulation of IL-2 predominantly in the CD4$\sp+$ and CD45RO$\sp+$ T cell subsets. This was similar to a number of PB T cell costimulatory molecules including CD26, CD43, CD44. Only CD28 costimulated IL-2 production from both CD45RA$\sp+$ and CD45RO$\sp+$ subpopulations.^ The GTPase Rho has been implicated in regulating integrin mediated stress fiber formation and anchorage dependent growth in fibroblasts, so studies were initiated to determine if Rho played a role in integrin dependent T cell function. In order to perform this, a technique based on scrape-loading was developed to incorporate macromolecules into PB T cells that maintained their functional activity. With this technique, C3 exoenzyme from Clostridium botulinum was incorporated into PB T cells. C3 ADP-ribosylates Rho proteins on Asn$\sp{41},$ which is in close proximity to the Rho effector domain, rendering it inactive. It was demonstrated that functional Rho is not required for basal or upregulated PB T cell adhesion to $\beta$1 integrin substrates, however PB T cell homotypic aggregation induced by PMA, which is an event mediated predominantly by the integrin $\rm\alpha L\beta2,$ was delayed. PB T cells lacking Rho function displayed altered cell morphology on $\beta$1 integrin ligands, producing stellate, dendritic-like pseudopodia. Rho activity was also found to be required for integrin dependent costimulation of proliferation. When intracellular accumulation of IL-2 was measured, inactivation of Rho prevented both integrin and CD28 costimulatory activity. Rho was identified to lie upstream of signals mediating PKC activation and Ca$\sp{++}$ fluxes, as PMA and ionomycin activation of PB T cells was unaffected by the inactivation of Rho. ^

Clinical, microbiological, and immunological markers of gingival and periodontal disease induction and progression

The potential impact of periodontal disease, a suspected risk factor for systemic diseases, presents challenges for health promotion and disease prevention strategies. This study examined clinical, microbiological, and immunological factors in a disease model to identify potential biomarkers that may be useful in predicting the onset and severity of both inflammatory and destructive periodontal disease. This project used an historical cohort design based on data obtained from 47 adult, female nonhuman primates followed over a 6-year period for 5 unique projects where the ligature-induced model of periodontitis was utilized. Standardization of protocols for sample collection allowed for comparison over time. Bleeding and pocket depth measures were selected as the dependent variables of relevance to humans based upon the literature and historical observations. Exposure variables included supragingival plaque, attachment level, total bacteria, black-pigmented bacteria, Gram-negative and Gram-positive bacteria, total IgG and IgA in crevicular fluid, specific IgG antibody in both crevicular fluid and serum, and IgG antibody to four select pathogenic microorganisms. Three approaches were used to analyze the data from this study. The first approach tested for differences in the means of the response variables within the group and among longitudinal observations within the group at each time point. The second approach examined the relationship among the clinical, microbiological, and immunological variables using correlation coefficients and stratified analyses. Multivariable models using GEE for repeated measures were produced as a predictive description of the induction and progression of gingivitis and periodontal disease. The multivariable models for bleeding (gingivitis) include supragingival plaque, total bacteria and total IgG while the second also contains supragingival plaque, Gram-positive bacteria, and total IgG. Two multivariable models emerged for periodontal disease. One multivariable model contains plaque, total bacteria, total IgG and attachment level. The second model includes black-pigmented bacteria, total bacteria, antibody to Campylobacter rectus, and attachment level. Utilization of the nonhuman primate model to prospectively examine causal hypotheses can provide a focus for human research on the mechanisms of progression from health to gingivitis to periodontitis. Ultimately, causal theories can guide strategies to prevent disease initiation and reduce disease severity. ^

Zoning and the built environment: A public health analysis of zoning in Austin, Texas

The built environment is part of the physical environment made by people and for people. Because the built environment is such a ubiquitous component of the environment, it acts as an important pathway in determining health outcomes. Zoning, a type of urban planning policy, is one of the most important mechanisms connecting the built environment to public health. This policy analysis research paper explores how zoning regulations in Austin, Texas promote or prohibit the development of a healthy built environment. A systematic literature review was obtained from Active Living Research, which contained literature published about the relationships between the built environment, physical activity, and health. The results of these studies identified the following four components of the built environment that were associated to health: access to recreational facilities, sprawl and residential density, land use mix, and sidewalks and their walkability. A hierarchy analysis was then performed to demonstrate the association between these aspects of the built environment and health outcomes such as obesity, cardiovascular disease, and general health. Once these associations had been established, the components of the built environment were adapted into the evaluation criteria used to conduct a public health analysis of Austin's zoning ordinance. A total of eighty-eight regulations were identified to be related to these components and their varying associations to human health. Eight regulations were projected to have a negative association to health, three would have both a positive and negative association simultaneously, and nine were indeterminable with the information obtained through the literature review. The remaining sixty-eight regulations were projected to be associated in a beneficial manner to human health. Therefore, it was concluded that Austin's zoning ordinance would have an overwhelmingly positive impact on the public's health based on identified associations between the built environment and health outcomes.^

Coping with advanced cancer: Caregivers and their patients

Background. Being diagnosed with advanced cancer may be one of the most difficult challenges a person faces. To help deal with advanced cancer, patients and caregivers lean towards the coping skills most familiar to them. Depending on the person, one’s coping may either help or perpetuate the problem. ^ Purpose. To identify predictors of negative coping skills among a group patients and caregivers, and to identify the predictors of prolonged grief among a group of providers, 6-months post loss. ^ Methods. Advanced cancer patients and caregivers were interviewed at the time of their enrollment (baseline) and caregivers were interviewed 6 months after the patient’s death (post-loss). Each participant was administered questionnaires regarding demographics, mental health disorders, mental health service use, coping methods, quality of life, and suicide attempts. Patients were asked about their treatment and diagnosis. Other patient-related information was obtained from medical charts. Moreover, caregivers were given an assessment regarding their alcohol and smoking history. ^ Results. Among White patients, positive coping skills were positively correlated with quality of life and negative coping skills were negatively correlated with quality of life. Gender, psychiatric disorders, suicidality, alcohol and smoking history, and treatment and diagnosis, were significantly related to negative coping skills; however this relationship only held for Hispanic patients. Gender and psychiatric disorders demonstrated predictive value for negative coping skills among all patients. On the other hand, psychiatric disorders, major depression, anxiety disorder, suicidality, and alcohol and smoking history, were not significant predictors of which caregivers experienced prolonged grief. ^ Conclusion. There was a significant relationship between quality of life and positive and negative coping skills of patients and negative coping skills for caregivers. Factors such as gender, psychiatric disorders, suicidality, alcohol and smoking history, and treatment and diagnosis demonstrated predictive value for negative coping skills in patients. ^

Latino perceptions of and barriers to preventive healthcare maintenance in the southwest United States

Between the 1990 and 2000 Censuses, the Latino population accounted for 40% of the increase in the nation’s total population. The growing population of Latinos underscores the importance for understanding factors that influence whether and how Latinos take care of their health. According to the U.S. Department of Human Health Service’s Office of Minority Health (OMH), Latinos are at greater risk for health disparities (2003). Factors such as lack of health insurance and access to preventive care play a major role in limiting Latino use of primary health care (Institute of Medicine, 2005). Other significant barriers to preventive health care maintenance behaviors have been identified in current literature such as primary care physician interaction, self-perceived health status, and socio-cultural beliefs and traditions (Rojas-Guyler, King, Montieth and 2008; Meir, Medina, and Ory, 2007; Black, 1999). Despite these studies, there remains less information regarding interpersonal perceptions, environmental dynamics and individual and cultural attitudes relevant to utilization of healthcare (Rojas-Guyler, King, Montieth and 2008; Aguirre-Molina, Molina and Zambrana, 2001). Understanding the perceptions of Latinos and the barriers to health care could directly affect healthcare delivery. Improved healthcare utilization among Latinos could reduce the long term health consequences of many preventable and manageable diseases. The purpose of this study was to explore Latino perceptions of U.S. health care and desired changes by Latinos in the U.S. healthcare system. The study had several objectives, including to explore perceived barriers to healthcare utilization and the resulting effects on health among Latinos, to describe culturally influenced attitudes about health care and use of health care services among Latinos, and to make recommendations for reducing disparities by improving healthcare and its utilization. The current study utilized data that were collected as part of a larger study to examine multidimensional, cross-cultural issues relevant to interactions between healthcare consumers and providers. Qualitative methods were used to analyze four Spanish-language focus group transcripts to interpret cultural influences on perceptions and beliefs among Latinos. Direct coding of transcript content was carried out by two reviewers, who conducted independent reviews of each transcript. Team members developed and refined thematic categories, positive and negative cases, and example text segments for each theme and sub-theme. Incongruities of interpretations were resolved through extensive discussion. Study participants included 44 self-identified Latino adults (16 male, 28 female) between age 18 and 64 years. Thirty seven (84.1%) of the participants were immigrants. The study population comprised eight ethnic subgroups. While 31% of the participants reported being employed on a full-time basis, only 18.4% had medical insurance that was private or employee sponsored. Five major themes regarding the perceptions and healthcare utilization behaviors of Latinos were consistent across all focus groups and were identified during the analysis. These were: (1) healthcare utilization, experience, and access; (2) organizational and institutional systems; (3) communication and interpersonal interactions between healthcare provider, staff, and patient; (4) Latinos’ perception of their own health status; (5) cultural influences on healthcare utilization, which included an innovation termed culturally-bound locus of control. Healthcare utilization was directly influenced by healthcare experience, access, current health status, and cultural factors and indirectly influenced by organizational systems. There was a strong interdependence among the main themes. The ability to communicate and interact effectively with healthcare providers and navigate healthcare systems (organizational and institutional access) significantly influenced the participant’s health care experience, most often (indirectly) impacting utilization negatively. ^ Research such as this can help to identify those perceptions and attitudes held by Latinos concerning utilization or underutilization of healthcare systems. These data suggest that for healthcare utilization to improve among Latinos, healthcare systems must create more culturally competent environments by providing better language services at the organizational level and more culturally sensitive providers at the interpersonal level. Better understanding of the complex interactions between these impediments can aid intervention developments, and help health providers and researchers in determining appropriate, adequate, and effective measurers of care to better increase overall health of Latinos.^