Rapid Liquid Chromatography-Tandem Mass Spectrometry Analysis of Two Urinary Oxidative Stress Biomarkers: 8-oxodG and 8-isoprostane.

Human biomonitoring of oxidative stress relies on urinary effect biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and 8-iso-prostaglandin F2α (8-isoprostane); however, their levels reported for similar populations are inconsistent in the scientific literature. One of the reasons is the multitude of analytical methods with varying degrees of selectivity used to quantify these biomarkers. Single-analyte methods are often used, requiring multiple injections that increase both time and cost. We developed a rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to quantify both urinary biomarkers simultaneously. A reversed-phase column using a gradient consisting of 0.1% acetic acid in water and 0.1% acetic acid in methanol/acetonitrile (70:30) was used for separation. The MS detection was by positive (8-oxodG) and negative (8-isoprostane) ion-mode by multiple reaction monitoring. Very low limit of detection (<20 pg/mL), excellent linearity (R2 > 0.999), accuracy (near 100%), and precision (CV < 10%) both for intra-day and inter-day experiments were achieved, as well as high recovery rates (>91%). Matrix effects were observed but were compensated by using internal standards. Our newly developed method is applicable for biomonitoring studies as well as large epidemiological studies investigating the effect of oxidative damage, as it requires only minimal clean up using solid phase extraction

Recent trends in chronic disease, impairment and disability among older adults in the United States

<p>Abstract</p> <p>Background</p> <p>To examine concurrent prevalence trends of chronic disease, impairment and disability among older adults.</p> <p>Methods</p> <p>We analyzed the 1998, 2004 and 2008 waves of the Health and Retirement Study, a nationally representative survey of older adults in the United States, and included 31,568 community dwelling adults aged 65 and over. Measurements include: prevalence of chronic diseases including hypertension, heart disease, stroke, diabetes, cancer, chronic lung disease and arthritis; prevalence of impairments, including impairments of cognition, vision, hearing, mobility, and urinary incontinence; prevalence of disability, including activities of daily living (ADLs) and instrumental activities of daily living (IADLs).</p> <p>Results</p> <p>The proportion of older adults reporting no chronic disease decreased from 13.1% (95% Confidence Interval [CI], 12.4%-13.8%) in 1998 to 7.8% (95% CI, 7.2%-8.4%) in 2008, whereas the proportion reporting 1 or more chronic diseases increased from 86.9% (95% CI, 86.2%-89.6%) in 1998 to 92.2% (95% CI, 91.6%-92.8%) in 2008. In addition, the proportion reporting 4 or more diseases increased from 11.7% (95% CI, 11.0%-12.4%) in 1998 to 17.4% (95% CI, 16.6%-18.2%) in 2008. The proportion of older adults reporting no impairments was 47.3% (95% CI, 46.3%-48.4%) in 1998 and 44.4% (95% CI, 43.3%-45.5%) in 2008, whereas the proportion of respondents reporting 3 or more was 7.2% (95% CI, 6.7%-7.7%) in 1998 and 7.3% (95% CI, 6.8%-7.9%) in 2008. The proportion of older adults reporting any ADL or IADL disability was 26.3% (95% CI, 25.4%-27.2%) in 1998 and 25.4% (95% CI, 24.5%-26.3%) in 2008.</p> <p>Conclusions</p> <p>Multiple chronic disease is increasingly prevalent among older U.S. adults, whereas the prevalence of impairment and disability, while substantial, remain stable.</p

Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation

Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1

Tuberculosis in HIV-Negative and HIV-Infected Patients in a Low-Incidence Country: Clinical Characteristics and Treatment Outcomes

BACKGROUND: In Switzerland and other developed countries, the number of tuberculosis (TB) cases has been decreasing for decades, but HIV-infected patients and migrants remain risk groups. The aim of this study was to compare characteristics of TB in HIV-negative and HIV-infected patients diagnosed in Switzerland, and between coinfected patients enrolled and not enrolled in the national Swiss HIV Cohort Study (SHCS). METHODS AND FINDINGS: All patients diagnosed with culture-confirmed TB in the SHCS and a random sample of culture-confirmed cases reported to the national TB registry 2000-2008 were included. Outcomes were assessed in HIV-infected patients and considered successful in case of cure or treatment completion. Ninety-three SHCS patients and 288 patients selected randomly from 4221 registered patients were analyzed. The registry sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the estimated number of HIV-infected patients not enrolled in the SHCS but reported to the registry 2000-2008 was 146 (95% CI 122-173). Coinfected patients were more likely to be from sub-Saharan Africa (51.5% versus 15.8%, P<0.0001) and to present disseminated disease (23.9% vs. 3.4%, P<0.0001) than HIV-negative patients. Coinfected patients not enrolled in the SHCS were asylum seekers or migrant workers, with lower CD4 cell counts at TB diagnosis (median CD4 count 79 cells/µL compared to 149 cells/µL among SHCS patients, P = 0.07). There were 6 patients (60.0%) with successful outcomes compared to 82 (88.2%) patients in the SHCS (P = 0.023). CONCLUSIONS: The clinical presentation of coinfected patients differed from HIV-negative TB patients. The number of HIV-infected patients diagnosed with TB outside the SHCS is similar to the number diagnosed within the cohort but outcomes are poorer in patients not followed up in the national cohort. Special efforts are required to address the needs of this vulnerable population

Upstream Solutions: Does the Supplemental Security Income Program Reduce Disability in the Elderly?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72843/1/j.1468-0009.2007.00512.x.pd

Consistency and precision of cancer reporting in a multiwave national panel survey

Abstract Background Many epidemiological studies rely on self-reported information, the accuracy of which is critical for unbiased estimates of population health. Previously, accuracy has been analyzed by comparing self-reports to other sources, such as cancer registries. Cancer is believed to be a well-reported condition. This paper uses novel panel data to test the consistency of cancer reports for respondents with repeated self-reports. Methods Data come from 978 adults who reported having been diagnosed with cancer in at least one of four waves of the Panel Study of Income Dynamics, 1999-2005. Consistency of cancer occurrence reports and precision of timing of onset were studied as a function of individual and cancer-related characteristics using logistic and ordered logistic models. Results Almost 30% of respondents gave inconsistent cancer reports, meaning they said they never had cancer after having said they did have cancer in a previous interview; 50% reported the year of diagnosis with a discrepancy of two or more years. More recent cancers were reported with a higher consistency and timing precision; cervical cancer was reported more inaccurately than other cancer types. Demographic and socio-economic factors were only weak predictors of reporting quality. Conclusions Results suggest that retrospective reports of cancer contain significant measurement error. The errors, however, are fairly random across different social groups, meaning that the results based on the data are not systematically biased by socio-economic factors. Even for health events as salient as cancer, researchers should exercise caution about the presumed accuracy of self-reports, especially if the timing of diagnosis is an important covariate.http://deepblue.lib.umich.edu/bitstream/2027.42/112656/1/12963_2010_Article_108.pd

Co-resident Parents and Young People Aged 15–34: Who Does What Housework?

Young adults are now more likely to co-reside with their parents than previous generations, but domestic work patterns among this family type are largely unexplored. This study addresses this issue using Australian Bureau of Statistics Time Use Surveys (1992, 1997, 2006) and Poisson–Gamma regression analyses. It examines patterns in and correlates of domestic labor in two-generation households in which young people aged 15–34 co-reside with their parents (n = 1,946 households comprised of 2,806 young people and 5,129 parents). It differentiates between routine indoor tasks (cooking, cleaning, laundry), non-routine tasks (outdoor work, household management and maintenance, car care) and grocery shopping. Predictors of more time in some domestic activities by young people include being in neither employment nor education/training (NEET), being older, having a single parent and being in a non-English speaking household (young women). Young people being NEET, or female, are associated with less cooking time for mothers, but in the main when young people do perform domestic activities, they do not relieve their parents of those same activities, suggesting more time is spent by the household in total

MPER-specific antibodies induce gp120 shedding and irreversibly neutralize HIV-1

Antibody-mediated gp120 shedding and HIV neutralization exhibit similar kinetics and thermodynamic requirements