Caffeine Intake and Its Association with Body Composition Measures and Macronutrient Intakes in People Living with HIV in the Miami Adult Studies on HIV Cohort.

Background: Caffeine acts as an anorexic agent, increases energy expenditures, and decreases total body fat mass, and could be detrimental to people living with HIV (PLWH). The objective of this study was to explore the relationship between caffeine consumption, body composition measures (fat mass, body mass index [BMI], and lean body mass [LBM]), nutrient intakes, CD4 counts, and HIV viral load in PLWH. Methods: A convenience sample of 130 PLWH was recruited and followed for 3 months. Caffeine intake, body composition measures, and nutrient intakes were collected using Modified Caffeine Consumption Questionnaire, bioimpedance analyses, and 24-hour dietary recalls. Linear regressions were used to analyze the baseline data for relationships between these variables. Linear mixed models (LMMs) were used to determine the overtime changes. Results: In baseline, linear regression analysis, higher caffeine consumption was associated with lower fat mass (ß = -0.994, p = 0.042). However, BMI and LBM did not show any significant association with caffeine intake. LMM analysis showed that the association between caffeine intake and fat mass strengthened overtime (ß = -1.987, p = 0.035). Baseline linear regression analysis showed that higher caffeine intake was significantly associated with lower caloric intakes from fat (ß = -1.902, p = 0.044) and lower total caloric intake (ß = -1.643, p = 0.042). However, LMM analysis showed that these associations diminished and lost significance overtime. There were no associations between body composition measures, nutrient intakes, CD4 counts, and HIV viral load. Conclusions: Caffeine intake adversely affected dietary intakes of macronutrients and total fat mass. Therefore, caffeine, a known anorectic, should be regulated in PLWH.

Magnetoelectric nanoparticles for delivery of antitumor peptides into glioblastoma cells by magnetic fields.

AIM: We studied externally controlled anticancer effects of binding tumor growth inhibiting synthetic peptides to magnetoelectric nanoparticles (MENs) on treatment of glioblastomas. METHODS: Hydrothermally synthesized 30-nm MENs had the core-shell composition of CoFe2O4@BaTiO3. Molecules of growth hormone-releasing hormone antagonist of the MIA class (MIA690) were chemically bound to MENs. In vitro experiments utilized human glioblastoma cells (U-87MG) and human brain microvascular endothelial cells. RESULTS: The studies demonstrated externally controlled high-efficacy binding of MIA690 to MENs, targeted specificity to glioblastoma cells and on-demand release of the peptide by application of d.c. and a.c. magnetic fields, respectively. CONCLUSION: The results support the use of MENs as an effective drug delivery carrier for growth hormone-releasing hormone antagonists in the treatment of human glioblastomas.

Erratum: Multiferroic coreshell magnetoelectric nanoparticles as NMR sensitive nanoprobes for cancer cell detection.

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Caffeine and Insomnia in People Living With HIV From the Miami Adult Studies on HIV (MASH) Cohort.

We explored the relationship between caffeine consumption, insomnia, and HIV disease progression (CD4+ T cell counts and HIV viral loads). Caffeine intake and insomnia levels were measured using the Modified Caffeine Consumption Questionnaire and the Pittsburgh Insomnia Rating Scale (PIRS) in 130 clinically stable participants who were living with HIV, taking antiretroviral therapy, and recruited from the Miami Adult Studies on HIV cohort. Linear regressions showed that caffeine consumption was significantly and adversely associated with distress score, quality-of-life score, and global PIRS score. Linear regression analyses also showed that global PIRS score was significantly associated with lower CD4+ T cell counts and higher HIV viral loads. Caffeine could have precipitated insomnia in susceptible people living with HIV, which could be detrimental to their disease progression states.

Multiferroic coreshell magnetoelectric nanoparticles as NMR sensitive nanoprobes for cancer cell detection.

Magnetoelectric (ME) nanoparticles (MENs) intrinsically couple magnetic and electric fields. Using them as nuclear magnetic resonance (NMR) sensitive nanoprobes adds another dimension for NMR detection of biological cells based on the cell type and corresponding particle association with the cell. Based on ME property, for the first time we show that MENs can distinguish different cancer cells among themselves as well as from their normal counterparts. The core-shell nanoparticles are 30 nm in size and were not superparamagnetic. Due to presence of the ME effect, these nanoparticles can significantly enhance the electric field configuration on the cell membrane which serves as a signature characteristic depending on the cancer cell type and progression stage. This was clearly observed by a significant change in the NMR absorption spectra of cells incubated with MENs. In contrast, conventional cobalt ferrite magnetic nanoparticles (MNPs) did not show any change in the NMR absorption spectra. We conclude that different membrane properties of cells which result in distinct MEN organization and the minimization of electrical energy due to particle binding to the cells contribute to the NMR signal. The nanoprobe based NMR spectroscopy has the potential to enable rapid screening of cancers and impact next-generation cancer diagnostic exams.

The Relationship Between Caffeine Intake and Immunological and Virological Markers of HIV Disease Progression in Miami Adult Studies on HIV Cohort.

Although there are many studies on adverse health effects of substance use and HIV disease progression, similar studies about caffeine consumption are few. In this study, we investigated the effects of caffeine on immunological and virological markers of HIV disease progression. A convenience sample of 130 clinically stable people living with HIV/AIDS on antiretroviral therapy (65 consuming ≤250 mg/day and 65 consuming >250 mg/day of caffeine) were recruited from the Miami Adult Studies on HIV (MASH) cohort. This study included a baseline and 3-month follow-up visit. Demographics, body composition measures, substance use, Modified Caffeine Consumption Questionnaire (MCCQ), and CD4 count and HIV viral load were obtained for all participants. Multivariable linear regression and Linear Mixed Models (LMMs) were used to understand the effect of caffeine consumption on CD4 count and HIV viral load. The mean age of the cohort was 47.9 ± 6.4 years, 60.8% were men and 75.4% were African Americans. All participants were on ART during both the visits. Mean caffeine intake at baseline was 337.6 ± 305.0 mg/day and did not change significantly at the 3-month follow-up visit. Multivariable linear regressions after adjustment for covariates showed significant association between caffeine consumption and higher CD4 count (ß = 1.532, p = 0.049) and lower HIV viral load (ß = -1.067, p = 0.048). LMM after adjustment for covariates showed that the relationship between caffeine and CD4 count (ß = 1.720, p = 0.042) and HIV viral load (ß = -1.389, p = 0.033) continued over time in a dose-response manner. Higher caffeine consumption was associated with higher CD4 cell counts and lower HIV viral loads indicating beneficial effects on HIV disease progression. Further studies examining biochemical effects of caffeine on CD4 cell counts and viral replication need to be done in the future.

Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort.

Background: Oxidative stress and reduced antioxidants may be a trigger for liver fibrogenesis. Reducing oxidative stress through higher antioxidant concentration may be a potential antifibrotic target.Objective: We aimed to investigate longitudinally whether plasma zinc, an antioxidant, is related to mitochondrial oxidative stress and the progression of liver fibrosis in the Miami Adult Studies in HIV (MASH) cohort.Methods: A prospective observational cohort study was conducted in 487 predominantly African American HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected adults with a mean ± SD age of 47.08 ± 7.67 y from the MASH cohort and followed for a median of 34 mo. Blood was collected for plasma zinc and measures were used to calculate the fibrosis-4 (FIB-4) score (aspartate amino transferase, alanine aminotransferase, and platelets). Plasma zinc deficiency was defined as <0.75 mg/L. Total DNA was extracted from peripheral blood mononuclear cells and mitochondrial DNA (mtDNA) 8-hydroxyguanosine (8-oxo-dG) was determined. Adjusted mixed models were used to assess the relations between zinc, stage of liver disease, and oxidative stress over time and compared between HIV and HIV/HCV groups.Results: Zinc concentrations (ß: -0.368, SE = 0.172; P = 0.033) and deficiency were associated with lower FIB-4 scores over time (ß: 0.381, SE = 0.118; P = 0.001). Compared with those who were not zinc deficient, zinc-deficient participants had an increased risk of having more-progressed liver disease (OR: 1.91; 95% CI: 1.15, 3.16; P = 0.012). Higher mtDNA 8-oxo-dG was associated with zinc deficiency (ß: 0.049, SE = 0.024; P = 0.044) and higher FIB-4 scores over time (ß: 0.597, SE = 0.168, P < 0.001).Conclusions: Lower plasma zinc concentrations were associated with liver fibrosis progression and mitochondrial oxidative stress in the HIV and HIV/HCV groups. Zinc may play a role in the impact of liver disease outcomes.

Lower Plasma Zinc Levels in Hyperglycemic People Living with HIV in the MASH cohort.

BACKGROUND: Zinc deficiency is prevalent in HIV and hyperglycemic patients. Antiretroviral therapy (ART) is a treatment to control HIV progression; however it increases the risk for hyperglycemia. The objective of this study was to assess the plasma zinc levels in hyperglycemic people living with HIV (PLWH). METHODS: Secondary analysis was conducted on the data from the Miami Adult Studies in HIV (MASH) cohort in Florida. Patients were categorized into hyperglycemic group (fasting blood glucose ≥100 mg/dL) and normal group (<100 mg/dL). RESULTS: Plasma zinc status and CD4 levels were lower in the hyperglycemic group, however the difference was not significant. There was a greater percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%). DISCUSSION: Although not statistically significant, related biomarkers such as plasma zinc levels and CD4 levels were lower in the hyperglycemic group. This may be due to the role zincplays in the immune system. Due to the fact that there was a higher percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%), it is important to monitor and manage blood glucose levels to minimize complications. Our findings along with previous findings suggest that zinc supplementation may benefit hyperglycemic PLWH.

Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles.

It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane's electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 µg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.

Cocaine Use and Liver Disease are Associated with All-Cause Mortality in the Miami Adult Studies in HIV (MASH) Cohort.

OBJECTIVE: Liver disease is a frequent cause of morbidity and mortality in HIV infection. We examined the relationship of cocaine use, liver disease progression and mortality in an HIV-infected cohort. METHODS: Consent was obtained from 487 HIV+ participants, a subset of the Miami Adult Studies on HIV (MASH) cohort. Participants were eligible if they were followed for at least two years, completed questionnaires on demographics and illicit drug use and had complete metabolic panels, CD4 cell counts and HIV-viral loads. FIB-4 was calculated and cut-off points were used for staging liver fibrosis. Death certificates were obtained. RESULTS: Participants were 65% men, 69% Black and 81% were on ART at recruitment. Cocaine was used by 32% of participants and 29% were HIV/HCV co-infected. Mean age was 46.9 ± 7.7 years, mean CD4 cell count was 501.9 ± 346.7 cells/µL and mean viral load was 2.75 ± 1.3 log10 copies/mL at baseline. During the follow-up, 27 patients died, with a mortality rate of 28.2/1000 person-year. Cocaine was used by 48% of those who died (specific mortality rate was 13/1000 person-year). Those who died were more likely to use cocaine (HR=3.8, P=0.006) and have more advanced liver fibrosis (HR=1.34, P<0.0001), adjusting for age, gender, CD4 cell count and HIV-viral load at baseline and over time. Among the HIV mono-infected participants, cocaine users were 5 times more likely to die (OR=5.09, P=0.006) than participants who did not use cocaine. CONCLUSION: Cocaine use and liver fibrosis are strong and independent predictors of mortality in HIV infected and HIV/HCV co-infected adults. Effective interventions to reduce cocaine use among people living with HIV (PHLW) are needed.

Health disparities between Black Hispanic and Black non-Hispanic cervical cancer cases in the USA.

BACKGROUND: Globally, cervical cancer is a major public health concern. Cervical cancer is the second most common cancer among women, resulting in approximately 500,000 cases per year. The purpose of this study is to compare disease characteristics between Black Hispanic (BH) and Black non-Hispanic (BNH) women in the US. MATERIALS AND METHODS: We used stratified random sampling to select cervical cancer patient records from the SEER database (1973-2009). We used Chi-square and independent samples t-test to examine differences in proportions and means. RESULTS: The sample included 2,000 cervical cancer cases of Black non-Hispanic and 91 Black Hispanic women. There were statistically significant differences between black Hispanic and black non- Hispanics in mean age at diagnosis (p<0.001), mean survival time (p<0.001), marital status (p<0.001), primary site of cancer (p<0.001); lymph node involvement (p<0.001); grading and differentiation (p<0.0001); and tumor behavior (p<0.001). Black women were more likely to develop cervical cancer and to have the highest mortality rates from the disease. CONCLUSIONS: Findings from this study show clear racial and ethnic disparities in cervical cancer incidence and prognosis that should be addressed.

Black Hispanic and Black non-Hispanic breast cancer survival data analysis with half-normal model application.

BACKGROUND: Breast cancer is the second leading cause of cancer death for women in the United States. Differences in survival of breast cancer have been noted among racial and ethnic groups, but the reasons for these disparities remain unclear. This study presents the characteristics and the survival curve of two racial and ethnic groups and evaluates the effects of race on survival times by measuring the lifetime data-based half-normal model. MATERIALS AND METHODS: The distributions among racial and ethnic groups are compared using female breast cancer patients from nine states in the country all taken from the National Cancer Institute's Surveillance, Epidemiology, and End RESULTS cancer registry. The main end points observed are: age at diagnosis, survival time in months, and marital status. The right skewed half-normal statistical probability model is used to show the differences in the survival times between black Hispanic (BH) and black non-Hispanic (BNH) female breast cancer patients. The Kaplan-Meier and Cox proportional hazard ratio are used to estimate and compare the relative risk of death in two minority groups, BH and BNH. RESULTS: A probability random sample method was used to select representative samples from BNH and BH female breast cancer patients, who were diagnosed during the years of 1973-2009 in the United States. The sample contained 1,000 BNH and 298 BH female breast cancer patients. The median age at diagnosis was 57.75 years among BNH and 54.11 years among BH. The results of the half-normal model showed that the survival times formed positive skewed models with higher variability in BNH compared with BH. The Kaplan-Meir estimate was used to plot the survival curves for cancer patients; this test was positively skewed. The Kaplan-Meier and Cox proportional hazard ratio for survival analysis showed that BNH had a significantly longer survival time as compared to BH which is consistent with the results of the half-normal model. CONCLUSIONS: The findings with the proposed model strategy will assist in the healthcare field to measure future outcomes for BH and BNH, given their past history and conditions. These findings may provide an enhanced and improved outlook for the diagnosis and treatment of breast cancer patients in the United States.

Statistical estimates from black non-Hispanic female breast cancer data.

BACKGROUND: The use of statistical methods has become an imperative tool in breast cancer survival data analysis. The purpose of this study was to develop the best statistical probability model using the Bayesian method to predict future survival times for the black non-Hispanic female breast cancer patients diagnosed during 1973- 2009 in the U.S. MATERIALS AND METHODS: We used a stratified random sample of black non-Hispanic female breast cancer patient data from the Surveillance Epidemiology and End RESULTS (SEER) database. Survival analysis was performed using Kaplan-Meier and Cox proportional regression methods. Four advanced types of statistical models, Exponentiated Exponential (EE), Beta Generalized Exponential (BGE), Exponentiated Weibull (EW), and Beta Inverse Weibull (BIW) were utilized for data analysis. The statistical model building criteria, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) were used to measure the goodness of fit tests. Furthermore, we used the Bayesian approach to obtain the predictive survival inferences from the best-fit data based on the exponentiated Weibull model. RESULTS: We identified the highest number of black non-Hispanic female breast cancer patients in Michigan and the lowest in Hawaii. The mean (SD), of age at diagnosis (years) was 58.3 (14.43). The mean (SD), of survival time (months) for black non- Hispanic females was 66.8 (30.20). Non-Hispanic blacks had a significantly increased risk of death compared to Black Hispanics (Hazard ratio: 1.96, 95%CI: 1.51-2.54). Compared to other statistical probability models, we found that the exponentiated Weibull model better fits for the survival times. By making use of the Bayesian method predictive inferences for future survival times were obtained. CONCLUSIONS: These findings will be of great significance in determining appropriate treatment plans and health-care cost allocation. Furthermore, the same approach should contribute to build future predictive models for any health related diseases.

Zinc and autophagy.

Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated. Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria. Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake.

Survival analysis for white non-Hispanic female breast cancer patients.

BACKGROUND: Race and ethnicity are significant factors in predicting survival time of breast cancer patients. In this study, we applied advanced statistical methods to predict the survival of White non-Hispanic female breast cancer patients, who were diagnosed between the years 1973 and 2009 in the United States (U.S.). MATERIALS AND METHODS: Demographic data from the Surveillance Epidemiology and End RESULTS (SEER) database were used for the purpose of this study. Nine states were randomly selected from 12 U.S. cancer registries. A stratified random sampling method was used to select 2,000 female breast cancer patients from these nine states. We compared four types of advanced statistical probability models to identify the best-fit model for the White non- Hispanic female breast cancer survival data. Three model building criterion were used to measure and compare goodness of fit of the models. These include Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC). In addition, we used a novel Bayesian method and the Markov Chain Monte Carlo technique to determine the posterior density function of the parameters. After evaluating the model parameters, we selected the model having the lowest DIC value. Using this Bayesian method, we derived the predictive survival density for future survival time and its related inferences. RESULTS: The analytical sample of White non-Hispanic women included 2,000 breast cancer cases from the SEER database (1973-2009). The majority of cases were married (55.2%), the mean age of diagnosis was 63.61 years (SD = 14.24) and the mean survival time was 84 months (SD = 35.01). After comparing the four statistical models, results suggested that the exponentiated Weibull model (DIC= 19818.220) was a better fit for White non-Hispanic females' breast cancer survival data. This model predicted the survival times (in months) for White non-Hispanic women after implementation of precise estimates of the model parameters. CONCLUSIONS: By using modern model building criteria, we determined that the data best fit the exponentiated Weibull model. We incorporated precise estimates of the parameter into the predictive model and evaluated the survival inference for the White non-Hispanic female population. This method of analysis will assist researchers in making scientific and clinical conclusions when assessing survival time of breast cancer patients.