State-level metabolic comorbidity prevalence and control among adults age 50-plus with diabetes: estimates from electronic health records and survey data in five states.

Background: Although treatment and control of diabetes can prevent complications and reduce morbidity, few data sources exist at the state level for surveillance of diabetes comorbidities and control. Surveys and electronic health records (EHRs) offer different strengths and weaknesses for surveillance of diabetes and major metabolic comorbidities. Data from self-report surveys suffer from cognitive and recall biases, and generally cannot be used for surveillance of undiagnosed cases.

Human herpesvirus 8 infection is associated with prostate cancer among IFNL4-ΔG carriers.

Background: The dinucleotide germline variant, rs368234815-ΔG, in the IFNL4 gene (IFNL4-ΔG) has been associated with prostate cancer among men at increased risk of sexually transmitted infections and reported to impair viral clearance. Human herpesvirus 8 (HHV-8) seropositivity has been associated with prostate cancer in Tobago.

Methods: We examined whether the association of HHV-8 with prostate cancer is IFNL4-ΔG-dependent among 728 IFNL4-ΔG-genotyped cases and 813 genotyped population-based controls from the NCI-Maryland Prostate Cancer Case-Control study.

Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions.

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan.

Methodological and Statistical Considerations for the National Children's Study.

The National Children's Study (NCS) statistics and item response theory group was tasked with promoting the quality of study measures and analysis. This paper provides an overview of six measurement and statistical considerations for the NCS: (1) Conceptual and Measurement Model; (2) Reliability; (3) Validity; (4) Measurement Invariance; (5) Interpretability of Scores; and (6) Burden of administration. The guidance was based primarily on recommendations of the International Society of Quality of Life Research.

Frontline Science: AMPK regulates metabolic reprogramming necessary for interferon production in human plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) play a crucial role in innate viral immunity as the most potent producers of type I interferons (IFN) in the human body. However, the metabolic regulation of IFN production in such vast quantity remains poorly understood. In this study, AMP-activated protein kinase (AMPK) is strongly implicated as a driver of metabolic reprogramming that the authors and others have observed in pDCs after activation via TLR7/9.

State-level estimation of diabetes and prediabetes prevalence: Combining national and local survey data and clinical data.

Many statisticians and policy researchers are interested in using data generated through the normal delivery of health care services, rather than carefully designed and implemented population-representative surveys, to estimate disease prevalence. These larger databases allow for the estimation of smaller geographies, for example, states, at potentially lower expense. However, these health care records frequently do not cover all of the population of interest and may not collect some covariates that are important for accurate estimation.

Decreased levels of the serum inflammatory biomarkers, sGP130, IL-6, sCRP and BAFF, are associated with increased likelihood of AIDS related Kaposi's sarcoma in men who have sex with men.

AIDS-related Kaposi's sarcoma (AIDS-KS) risk remains substantially elevated compared with the general population, even among patients who receive effective combination antiretroviral therapy. This study investigated the role of inflammatory and immune activating biomarkers in AIDS-KS in men who have sex with men in the Multicenter AIDS Cohort study between 1984 and 2010. Concentrations of 24 serum biomarkers; IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, sGP130, sIL-2Rα, sIL-6R, eotaxin, MCP-1, MCP4, MIP 1β, TARC, BLC-BCA1, IP-10, GM-CSF, IFN-γ, BAFF, sCD14, CD27, sTNFR-2, sCRP, and TNF-α were tested longitudinally in 1,501 men.

Novel Methods and Data Sources for Surveillance of State-Level Diabetes and Prediabetes Prevalence.

States bear substantial responsibility for addressing the rising rates of diabetes and prediabetes in the United States. However, accurate state-level estimates of diabetes and prediabetes prevalence that include undiagnosed cases have been impossible to produce with traditional sources of state-level data. Various new and nontraditional sources for estimating state-level prevalence are now available.

Modified Terminal Restriction Fragment Analysis for Quantifying Telomere Length Using In-gel Hybridization.

There are several different techniques for measuring telomere length, each with their own advantages and disadvantages. The traditional approach, Telomere Restriction Fragment (TRF) analysis, utilizes a DNA hybridization technique whereby genomic DNA samples are digested with restriction enzymes, leaving behind telomere DNA repeats and some sub-telomeric DNA. These are separated by agarose gel electrophoresis, transferred to a filter membrane and hybridized to oligonucleotide probes tagged with either chemiluminescence or radioactivity to visualize telomere restriction fragments.

Epinephrine promotes COX-2-dependent immune suppression in myeloid cells and cancer tissues.

Activation of the sympathetic nervous system (e.g., due to stress) has been implicated in cancer progression and recurrence, but its cancer-promoting effects have been variable between different studies.

Regulatory T Cell Effect on CD8 T Cell Responses to Human Herpesvirus 8 Infection and Development of Kaposi's Sarcoma.

We assessed CD8 T cell reactivity to human herpesvirus 8 (HHV-8; Kaposi's sarcoma [KS]-associated herpesvirus) and the role of CD4CD25FoxP3 regulatory T cells (Treg) in HHV-8- and HIV-coinfected participants of the Multicenter AIDS Cohort Study who did or did not develop KS. There were similarly low CD8 T cell interferon-γ responses to MHC class I-restricted epitopes of HHV-8 lytic and latent proteins over 5.7 years before KS in participants who developed KS compared to those who did not.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

Background: Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important.

Human herpesvirus 8 infection contributes to a T helper 2 immune response in men from Tobago with prostate cancer.

Objectives: To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer.

Methods: The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth.

Human herpesvirus 8 establishes a latent infection in prostates of Tobago men resulting in increased macrophage infiltration.

Background: The Caribbean island of Tobago, which is 97% African ancestry, has one of the highest rates of prostate cancer in the world. We have previously reported that human herpesvirus 8 (HHV-8) infection is significantly associated with prostate cancer in Tobago. In this study, we extend those results testing the hypothesis that HHV-8 seropositive Tobagonian men have a chronic HHV-8 infection in their prostates that is associated with increased inflammation.

Merkel Cell Polyomavirus Small T Antigen Induces Cancer and Embryonic Merkel Cell Proliferation in a Transgenic Mouse Model.

Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre-mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days.

Association between free testosterone levels and anal human papillomavirus types 16/18 infections in a cohort of men who have sex with men.

Background: Human papillomavirus (HPV) types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs). Overall, IAC rates are highest among men who have sex with men (MSM), especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting.

Human herpesvirus 8 seroconversion in a population-based cohort of men in Tobago.

Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to <22.

Prospective study of human herpesvirus type 8 serostatus and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial.

Background: Human herpesvirus type 8 (HHV-8), a gamma herpesvirus associated with Kaposi's sarcoma, has been proposed as a candidate risk factor for prostate cancer (PCa) because of its detection in benign and malignant prostate specimens, and its relation with histologic prostatic inflammation. We investigated the possible relation between pre-diagnostic HHV-8 infection and PCa risk in a case-control study sampled from the placebo arm of the Prostate Cancer Prevention Trial.

Methods: We defined cases as men with a confirmed diagnosis of PCa after visit 2 (n = 315) and controls as men not diagnosed with PCa during the trial who also had a negative end-of-study prostate biopsy (n = 315).

Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis.

Human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is an oncogenic gammaherpesvirus that primarily infects cells of the immune and vascular systems. HHV-8 interacts with and targets professional antigen presenting cells and influences their function. Infection alters the maturation, antigen presentation, and immune activation capabilities of certain dendritic cells (DC) despite non-robust lytic replication in these cells.

Human herpesvirus 8 induces polyfunctional B lymphocytes that drive Kaposi's sarcoma.

Unlabelled: Kaposi's sarcoma (KS) is an unusual neoplasia wherein the tumor consists primarily of endothelial cells infected with human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) that are not fully transformed but are instead driven to excess proliferation by inflammatory and angiogenic factors. This oncogenic process has been postulated but unproven to depend on a paracrine effect of an abnormal excess of host cytokines and chemokines produced by HHV-8-infected B lymphocytes. Using newly developed measures for intracellular detection of lytic cycle proteins and expression of cytokines and chemokines, we show that HHV-8 targets a range of naive B cell, IgM memory B cell, and plasma cell-like populations for infection and induction of interleukin-6, tumor necrosis factor alpha, macrophage inhibitory protein 1α, macrophage inhibitory protein 1β, and interleukin-8 in vitro and in the blood of HHV-8/HIV-1-coinfected subjects with KS.

Human herpesvirus 8 glycoprotein B binds the entry receptor DC-SIGN.

We have previously shown that human herpesvirus 8 (HHV-8) uses DC-SIGN as an entry receptor for dendritic cells, macrophages and B cells. The viral attachment protein for DC-SIGN is unknown. HHV-8 virions contain five conserved herpesvirus glycoproteins, a single unique glycoprotein, and two predicted glycoproteins.

Preoperative inflammatory biomarkers and neurovegetative symptoms in peritoneal carcinomatosis patients.

Background: Inflammation plays a central role in peritoneal carcinomatosis (PC) etiology and progression, and circulating levels of inflammatory biomarkers prior to surgery predict progression-free and overall survival in PC patients. Depression and fatigue are prevalent among PC patients, and experimental research shows that these symptoms may be mediated by proinflammatory cytokines. As yet unstudied is the possibility that the heightened levels of inflammatory markers in PC patients may contribute to their experience of common neurovegetative symptoms.