Obesity and Serum High Sensitivity C-Reactive Protein Levels Among Elderly Turkish Immigrants in the Netherlands with Type 2 Diabetes

The study examined the associations of anthropometric measures of obesity with high sensitivity C-reactive protein (hs-CRP) levels in Turkish immigrants with type 2 diabetes (T2D) living in the Netherlands. A total of 110 participants, physician-diagnosed with T2D, aged 30 years and older were recruited from multiple sources from The Hague, Netherlands. Serum hs-CRP levels were measured with immunoturbidimetric assay. Glycated hemoglobin (A1C) was determined by high-pressure liquid chromatography. Measures of obesity: body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were determined. Statistical analysis included descriptive statistics, Pearson’s correlations and multiple linear regressions (MLR) stratified by gender. Hs-CRP was log transformed to achieve normality. Subjects with hs-CRP levels >10 mg/L (n = 17) were excluded from the analysis. Females had a higher BMI (p = 0.007), HC (p < 0.001), and WHtR (p = 0.011) as compared to males. Conversely, males had a higher weight (p = 0.007), and WHR (p < 0.001) than females. MLR showed that after controlling for covariates, log hs-CRP was positively associated with BMI (B = 0.039, SE = 0.019, β = 0.287, p < 0.05), WC (B = 0.025, SE = 0.011, β = 0.332, p < 0.05) and WHtR (B = 4.015, SE = 1.464, β = 0.376, p < 0.01) in females only. Gender-specific associations between obesity measures and hs-CRP level need to be further investigated in the Turkish immigrant population. Hs-CRP assessment may be added as a standard of care for T2D treatment within this population.

Specificity, stability and comparative physiology of coral-Symbiodinium mutualisms: Evaluating the potential for acclimation and/or adaptation in reef corals

The relationship between reef corals and endosymbiotic dinoflagellates is fundamental to the existence of coral reefs. To evaluate the fidelity of coral-Symbiodinium mutualisms, corals maintained in aquaria for years were analyzed by denaturant gradient gel electrophoresis (DGGE). Comparing Symbiodinium populations of captive aquarium colonies with known associations in nature is a practical way of examining partner flexibility. The finding of "normal" symbiont populations in corals existing under highly variable conditions supports the premise that most coral colonies possess stable associations. High sensitivity real-time PCR (rtPCR) was used to evaluate background populations of the putatively stress-tolerant Symbiodinium D in reef corals of the Caribbean. Analyses of samples collected during periods of environmental stability indicate the ability of Symbiodinium D to associate with a wider diversity of host taxa than previously recognized. To gain a broader perspective with regard to the ecology of Symbiodinium D1a, rtPCR and DGGE were used to evaluate the symbiont populations of reef corals from Barbados before and after the 2005 mass coral bleaching. Background populations were observed in 56% of the host genera prior to observations of bleaching. These findings indicate that 'stress', not 'bleaching', caused the displacement of 'natural' symbiont population and the opportunistic proliferation of D1a in many host taxa. Of the 12 host taxa monitored before and after the bleaching event, there was a 40% increase in colonies hosting Symbiodinium D1a. Together, these studies elucidate the mechanism responsible for recent observations reporting the emergence of Symbiodinium D following thermal disturbances. These observations are now most easily explained as the disproportionate growth of existing in hospite symbiont populations, rather than novel symbiont acquisition subsequent to bleaching. To evaluate the comparative "fitness" of corals able to host multiple symbiont types, rates of calcification were measured in P. verrucosa hosting either Symbiodinium C1b-c or D1 at elevated temperature. Rates of calcification decreased significantly for both host-symbiont combinations, but differences attributable to symbiont composition were not detected. This research improves our knowledge of the symbiosis biology and ecology of reef corals and contributes information necessary to most accurately predict the response of these ecosystems to global climate changes.

Development of micro immunosensors to study genomic and proteomic biomarkers related to cancer and Alzheimer's disease

A report from the National Institutes of Health defines a disease biomarker as a “characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Early diagnosis is a crucial factor for incurable disease such as cancer and Alzheimer’s disease (AD). During the last decade researchers have discovered that biochemical changes caused by a disease can be detected considerably earlier as compared to physical manifestations/symptoms. In this dissertation electrochemical detection was utilized as the detection strategy as it offers high sensitivity/specificity, ease of operation, and capability of miniaturization and multiplexed detection. Electrochemical detection of biological analytes is an established field, and has matured at a rapid pace during the last 50 years and adapted itself to advances in micro/nanofabrication procedures. Carbon fiber microelectrodes were utilized as the platform sensor due to their high signal to noise ratio, ease and low-cost of fabrication, biocompatibility, and active carbon surface which allows conjugation with biorecognition moieties. This dissertation specifically focuses on the detection of 3 extensively validated biomarkers for cancer and AD. Firstly, vascular endothelial growth factor (VEGF) a cancer biomarker was detected using a one-step, reagentless immunosensing strategy. The immunosensing strategy allowed a rapid and sensitive means of VEGF detection with a detection limit of about 38 pg/mL with a linear dynamic range of 0–100 pg/mL. Direct detection of AD-related biomarker amyloid beta (Aβ) was achieved by exploiting its inherent electroactivity. The quantification of the ratio of Aβ1-40/42 (or Aβ ratio) has been established as a reliable test to diagnose AD through human clinical trials. Triple barrel carbon fiber microelectrodes were used to simultaneously detect Aβ1-40 and Aβ1-42 in cerebrospinal fluid from rats within a detection range of 100nM to 1.2μM and 400nM to 1μM respectively. In addition, the release of DNA damage/repair biomarker 8-hydroxydeoxyguanine (8-OHdG) under the influence of reactive oxidative stress from single lung endothelial cell was monitored using an activated carbon fiber microelectrode. The sensor was used to test the influence of nicotine, which is one of the most biologically active chemicals present in cigarette smoke and smokeless tobacco.

Cardiovascular risk factors in Turkish immigrants with type 2 diabetes living in the Netherlands

The cross sectional study investigated the association of tobacco smoke, vitamin D status, anthropometric parameters, and kidney function in Turkish immigrants with type 2 diabetes (T2D) living in the Netherlands. Study sample included a total of 110 participants aged 30 years and older (males= 46; females= 64). Serum cotinine, a biomarker for smoke exposure, was measured with a solid-phase competitive chemiluminescent immunoassay. Serum 25-hydroxyvitamin D [25(OH)D] was determined by electrochemiluminescence immunoassay (ECLIA). Measures of obesity including: body weight, body mass index (BMI), waist circumference (WC), and hip circumference (HC) were measured. Waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were calculated. Urine albumin was measured by immunoturbidimetric assay. Urine creatinine was determined using the Jaffe method. All statistical analyses were performed using SPSS, version 19.0 (SPSS Inc., Chicago, IL, USA). Independent samples t-test, chi-squared tests, multiple linear regression and logistic regression analysis were used. Cotinine levels were positively associated with cholesterol to HDL ratio and atherosclerosis-index. Serum 25(OH)D levels were negatively associated with diastolic blood pressure. Gender-specific associations between anthropometric measures and high sensitivity C-reactive protein (hs-CRP) levels were observed. Hs-CRP was positively associated with WC and WHR in males and WHtR in females. Microalbuminuria (MAU), as determined by albumin-to-creatinine ratio, was present in 21% of the Turkish immigrants with T2D. Participants with hypertension were 6.58 times more likely (adjusted odds ratio) to have positive MAU as compared to normotensive participants. Our findings indicate that serum cotinine, 25(OH)D, hs-CRP, and MAU may be assessed as a standard of care for T2D management in the Turkish immigrant population. Further research should be conducted following cohorts to determine the effects of these biomarkers on CVD morbidity and mortality.

Comparison of coronary heart disease risk factors in foreign -born and United States-born Afro Caribbean Americans and African Americans in south Florida

In a cross-sectional study design, risk factors for coronary heart disease (CHD) were evaluated in three groups: 66 Afro Caribbeans (FBCA) living in the US for less than 10 years, 62 US-born Afro Caribbean (USBCA) and 61 African American (AA) adults (18–40 years), with equal numbers of males and females in each group. Socio-demographic, dietary, anthropometric and blood pressure data were collected. Fasting blood glucose, blood lipids and high-sensitivity C-reactive protein (hs-CRP) were determined. ^ The USBCA and AA participants compared to the FBCA participants consumed significantly (p < 0.05) more mean total fat (g) (66.3 ± 41.7 and 73.0 ± 47.8 vs. 52.8 ± 32.3), saturated fat (g) (23.1 ± 14.9 and 24.9 ± 15.8 vs. 18.6 ± 11.5), percent energy from fat (%) (33.1 ± 6.5 and 31.4 ± 6.4 vs. 29.3 ± 6.8), fat servings (1.8 ± 1.2 and 1.5 ± 1.0 vs. 1.2 ± 0.9), dietary cholesterol (mg) (220.4 ± 161.9 and 244.1 ± 155.0 vs. 168.8 ± 114.0) and sodium (mg) (2245.2 ± 1238.3 and 2402.6 ± 1359.3 vs. 1838.0 ± 983.4) and less than 2 servings of fruits per day (%) (86.9 and 94.9 vs. 78.5). These differences were more pronounced in males compared to females and remained after correcting for age. Also, the percentages of USBCA and AA participants who were obese (17.1% and 23.0%, respectively) were significantly (p < 0.05) higher compared to FBCA (7.6%) participants. More USBCA and AA than FBCA individuals smoked cigarettes (4.8% and 6.6% vs. 0.0%) and consumed alcoholic beverages (29.0% and 50.8% vs. 24.2%). The mean hs-CRP level of the AA participants (2.2 ± 2.7 mg/L) was significantly (p < 0.01) higher compared to the FBCA (1.1 ± 1.3 mg/L) and USBCA (1.3 ± 1.6 mg/L) participants. ^ The FBCA participants had a better CHD risk profile than the USBCA and AA participants. Focus should be placed on the ethnic and cultural differences in a population to better understand the variations in health indicators among different ethnic groups of the same race. This focus can provide healthcare professionals and policy planners with the opportunity to develop culturally sensitive programs and strategies for the improvement of health outcomes. ^

Assessment of the occurrence and potential risks of antibiotics and their metabolites in South Florida waters using liquid chromatography tandem mass spectrometry

An automated on-line SPE-LC-MS/MS method was developed for the quantitation of multiple classes of antibiotics in environmental waters. High sensitivity in the low ng/L range was accomplished by using large volume injections with 10-mL of sample. Positive confirmation of analytes was achieved using two selected reaction monitoring (SRM) transitions per antibiotic and quantitation was performed using an internal standard approach. Samples were extracted using online solid phase extraction, then using column switching technique; extracted samples were immediately passed through liquid chromatography and analyzed by tandem mass spectrometry. The total run time per each sample was 20 min. The statistically calculated method detection limits for various environmental samples were between 1.2 and 63 ng/L. Furthermore, the method was validated in terms of precision, accuracy and linearity. ^ The developed analytical methodology was used to measure the occurrence of antibiotics in reclaimed waters (n=56), surface waters (n=53), ground waters (n=8) and drinking waters (n=54) collected from different parts of South Florida. In reclaimed waters, the most frequently detected antibiotics were nalidixic acid, erythromycin, clarithromycin, azithromycin trimethoprim, sulfamethoxazole and ofloxacin (19.3-604.9 ng/L). Detection of antibiotics in reclaimed waters indicates that they can't be completely removed by conventional wastewater treatment process. Furthermore, the average mass loads of antibiotics released into the local environment through reclaimed water were estimated as 0.248 Kg/day. Among the surface waters samples, Miami River (reaching up to 580 ng/L) and Black Creek canal (up to 124 ng/L) showed highest concentrations of antibiotics. No traces of antibiotics were found in ground waters. On the other hand, erythromycin (monitored as anhydro erythromycin) was detected in 82% of the drinking water samples (n.d-66 ng/L). The developed approach is suitable for both research and monitoring applications.^ Major metabolites of antibiotics in reclaimed wates were identified and quantified using high resolution benchtop Q-Exactive orbitrap mass spectrometer. A phase I metabolite of erythromycin was tentatively identified in full scan based on accurate mass measurement. Using extracted ion chromatogram (XIC), high resolution data-dependent MS/MS spectra and metabolic profiling software the metabolite was identified as desmethyl anhydro erythromycin with molecular formula C36H63NO12 and m/z 702.4423. The molar concentration of the metabolite to erythromycin was in the order of 13 %. To my knowledge, this is the first known report on this metabolite in reclaimed water. Another compound acetyl-sulfamethoxazole, a phase II metabolite of sulfamethoxazole was also identified in reclaimed water and mole fraction of the metabolite represent 36 %, of the cumulative sulfamethoxazole concentration. The results were illustrating the importance to include metabolites also in the routine analysis to obtain a mass balance for better understanding of the occurrence, fate and distribution of antibiotics in the environment. ^ Finally, all the antibiotics detected in reclaimed and surface waters were investigated to assess the potential risk to the aquatic organisms. The surface water antibiotic concentrations that represented the real time exposure conditions revealed that the macrolide antibiotics, erythromycin, clarithromycin and tylosin along with quinolone antibiotic, ciprofloxacin were suspected to induce high toxicity to aquatic biota. Preliminary results showing that, among the antibiotic groups tested, macrolides posed the highest ecological threat, and therefore, they may need to be further evaluated with, long-term exposure studies considering bioaccumulation factors and more number of species selected. Overall, the occurrence of antibiotics in aquatic environment is posing an ecological health concern.^

The H I chronicles of LITTLE THINGS blue compact dwarf galaxies

Star formation occurs when the gas (mostly atomic hydrogen; H I) in a galaxy becomes disturbed, forming regions of high density gas, which then collapses to form stars. In dwarf galaxies it is still uncertain which processes contribute to star formation and how much they contribute to star formation. Blue compact dwarf (BCD) galaxies are low mass, low shear, gas rich galaxies that have high star formation rates when compared to other dwarf galaxies. What triggers the dense burst of star formation in BCDs but not other dwarfs is not well understood. It is often suggested that BCDs may have their starburst triggered by gravitational interactions with other galaxies, dwarf-dwarf galaxy mergers, or consumption of intergalactic gas. However, there are BCDs that appear isolated with respect to other galaxies, making an external disturbance unlikely.^ Here, I study six apparently isolated BCDs from the LITTLE THINGS sample in an attempt to understand what has triggered their burst of star formation. LITTLE THINGS is an H I survey of 41 dwarf galaxies. Each galaxy has high angular and velocity resolution H I data from the Very Large Array (VLA) telescope and ancillary stellar data. I use these data to study the detailed morphology and kinematics of each galaxy, looking for signatures of starburst triggers. In addition to the VLA data, I have collected Green Bank Telescope data for the six BCDs. These high sensitivity, low resolution data are used to search the surrounding area of each galaxy for extended emission and possible nearby companion galaxies.^ The VLA data show evidence that each BCD has likely experienced some form of external disturbance despite their apparent isolation. These external disturbances potentially seen in the sample include: ongoing/advanced dwarf-dwarf mergers, an interaction with an unknown external object, and external gas consumption. The GBT data result in no nearby, separate H I companions at the sensitivity of the data. These data therefore suggest that even though these BCDs appear isolated, they have not been evolving in isolation. It is possible that these external disturbances may have triggered the starbursts that defines them as BCDs.^

Serum Adiponectin and Ghrelin, Metabolic Syndrome and Diabetes Status in Cuban Americans

Purpose: Metabolic syndrome (MetS) is associated with the development of cardiovascular disease (CVD) and type 2 diabetes. Decreases in circulating adiponectin and ghrelin have been associated with MetS. Our primary aim was to evaluate the relationship of MetS with adiponectin and ghrelin for Cuban Americans with and without type 2 diabetes. Methods: Cross-sectional study of 367 adults, self identified as Cuban extraction and randomly recruited from a mailing list of Broward and Miami-Dade counties. Fasted whole blood for adiponectin (ADPN) was collected using K3EDTA tubes and measured by ELISA. Ghrelin was assayed with fasted blood plasma by Enzyme Immunometric Assay. MetS and 10-year risk for coronary heart disease (CHD) were determined using the ATP III criteria. Results: Adiponectin (F=51.8, R2 =0.21 p<0.001) and ghrelin (F=12.77, R 2 =0.06, p<0.001) differed by diabetes status (ANOVA) not age and gender. In stepwise linear regression models triglyceride levels ≥ 150 mg/dL negatively corresponded (coefficient = -0.23) with ghrelin levels for persons without diabetes (F=7.45, R2 =0.053, p=0.007); abdominal obesity and fasting plasma glucose predicted high sensitivity C-reactive protein (hs-CRP) for persons with and without diabetes (F=16.3, R2 = 0.144, p <0.001). Conclusion: Low ghrelin levels were associated with MetS regardless of diabetes status. High adiponectin levels were related to a low probability for those without diabetes only. There was a positive association of hs-CRP with BMI, MetS and number of MetS components.

Assessment of the Occurrence and Potential Risks of Antibiotics and their Metabolites in South Florida Waters Using Liquid Chromatography Tandem Mass Spectrometry

An automated on-line SPE-LC-MS/MS method was developed for the quantitation of multiple classes of antibiotics in environmental waters. High sensitivity in the low ng/L range was accomplished by using large volume injections with 10-mL of sample. Positive confirmation of analytes was achieved using two selected reaction monitoring (SRM) transitions per antibiotic and quantitation was performed using an internal standard approach. Samples were extracted using online solid phase extraction, then using column switching technique; extracted samples were immediately passed through liquid chromatography and analyzed by tandem mass spectrometry. The total run time per each sample was 20 min. The statistically calculated method detection limits for various environmental samples were between 1.2 and 63 ng/L. Furthermore, the method was validated in terms of precision, accuracy and linearity. The developed analytical methodology was used to measure the occurrence of antibiotics in reclaimed waters (n=56), surface waters (n=53), ground waters (n=8) and drinking waters (n=54) collected from different parts of South Florida. In reclaimed waters, the most frequently detected antibiotics were nalidixic acid, erythromycin, clarithromycin, azithromycin trimethoprim, sulfamethoxazole and ofloxacin (19.3-604.9 ng/L). Detection of antibiotics in reclaimed waters indicates that they can’t be completely removed by conventional wastewater treatment process. Furthermore, the average mass loads of antibiotics released into the local environment through reclaimed water were estimated as 0.248 Kg/day. Among the surface waters samples, Miami River (reaching up to 580 ng/L) and Black Creek canal (up to 124 ng/L) showed highest concentrations of antibiotics. No traces of antibiotics were found in ground waters. On the other hand, erythromycin (monitored as anhydro erythromycin) was detected in 82% of the drinking water samples (n.d-66 ng/L). The developed approach is suitable for both research and monitoring applications. Major metabolites of antibiotics in reclaimed wates were identified and quantified using high resolution benchtop Q-Exactive orbitrap mass spectrometer. A phase I metabolite of erythromycin was tentatively identified in full scan based on accurate mass measurement. Using extracted ion chromatogram (XIC), high resolution data-dependent MS/MS spectra and metabolic profiling software the metabolite was identified as desmethyl anhydro erythromycin with molecular formula C36H63NO12 and m/z 702.4423. The molar concentration of the metabolite to erythromycin was in the order of 13 %. To my knowledge, this is the first known report on this metabolite in reclaimed water. Another compound acetyl-sulfamethoxazole, a phase II metabolite of sulfamethoxazole was also identified in reclaimed water and mole fraction of the metabolite represent 36 %, of the cumulative sulfamethoxazole concentration. The results were illustrating the importance to include metabolites also in the routine analysis to obtain a mass balance for better understanding of the occurrence, fate and distribution of antibiotics in the environment. Finally, all the antibiotics detected in reclaimed and surface waters were investigated to assess the potential risk to the aquatic organisms. The surface water antibiotic concentrations that represented the real time exposure conditions revealed that the macrolide antibiotics, erythromycin, clarithromycin and tylosin along with quinolone antibiotic, ciprofloxacin were suspected to induce high toxicity to aquatic biota. Preliminary results showing that, among the antibiotic groups tested, macrolides posed the highest ecological threat, and therefore, they may need to be further evaluated with, long-term exposure studies considering bioaccumulation factors and more number of species selected. Overall, the occurrence of antibiotics in aquatic environment is posing an ecological health concern.

Bionano Electronics: Magneto-Electric Nanoparticles for Drug Delivery, Brain Stimulation and Imaging Applications

Nanoparticles are often considered as efficient drug delivery vehicles for precisely dispensing the therapeutic payloads specifically to the diseased sites in the patient’s body, thereby minimizing the toxic side effects of the payloads on the healthy tissue. However, the fundamental physics that underlies the nanoparticles’ intrinsic interaction with the surrounding cells is inadequately elucidated. The ability of the nanoparticles to precisely control the release of its payloads externally (on-demand) without depending on the physiological conditions of the target sites has the potential to enable patient- and disease-specific nanomedicine, also known as Personalized NanoMedicine (PNM). In this dissertation, magneto-electric nanoparticles (MENs) were utilized for the first time to enable important functions, such as (i) field-controlled high-efficacy dissipation-free targeted drug delivery system and on-demand release at the sub-cellular level, (ii) non-invasive energy-efficient stimulation of deep brain tissue at body temperature, and (iii) a high-sensitivity contrasting agent to map the neuronal activity in the brain non-invasively. First, this dissertation specifically focuses on using MENs as energy-efficient and dissipation-free field-controlled nano-vehicle for targeted delivery and on-demand release of a anti-cancer Paclitaxel (Taxol) drug and a anti-HIV AZT 5’-triphosphate (AZTTP) drug from 30-nm MENs (CoFe2O4-BaTiO3) by applying low-energy DC and low-frequency (below 1000 Hz) AC fields to separate the functions of delivery and release, respectively. Second, this dissertation focuses on the use of MENs to non-invasively stimulate the deep brain neuronal activity via application of a low energy and low frequency external magnetic field to activate intrinsic electric dipoles at the cellular level through numerical simulations. Third, this dissertation describes the use of MENs to track the neuronal activities in the brain (non-invasively) using a magnetic resonance and a magnetic nanoparticle imaging by monitoring the changes in the magnetization of the MENs surrounding the neuronal tissue under different states. The potential therapeutic and diagnostic impact of this innovative and novel study is highly significant not only in HIV-AIDS, Cancer, Parkinson’s and Alzheimer’s disease but also in many CNS and other diseases, where the ability to remotely control targeted drug delivery/release, and diagnostics is the key.