Effects of Landscape Fragmentation and Climate on Lyme Disease Incidence in the Northeastern United States

Lyme disease is the most frequently reported vector borne illness in the United States, and incidences are increasing steadily year after year. This study explores the influence of landscape (e.g., land use pattern and landscape fragmentation) and climatic factors (e.g., temperature and precipitation) at a regional scale on Lyme disease incidence. The study area includes thirteen states in the Northeastern United States. Lyme disease incidence at county level for the period of 2002–2006 was linked with several key landscape and climatic variables in a negative binomial regression model. Results show that Lyme disease incidence has a relatively clear connection with regional landscape fragmentation and temperature. For example, more fragmentation between forests and residential areas results in higher local Lyme disease incidence. This study also indicates that, for the same landscape, some landscape variables derived at a particular scale show a clearer connection to Lyme disease than do others. In general, the study sheds more light on connections between Lyme disease incidence and climate and landscape patterns at the regional scale. Integrating findings of this regional study with studies at a local scale will further refine understanding of the pattern of Lyme disease as well as increase our ability to predict, prevent, and respond to disease.     

From geochemical background determination to pollution assessment of heavy metals in sediments and soils

Establishing geochemical background concentrations to distinguish the natural background from anthropogenic concentrations of heavy metals in sediments and soils is necessary to develop guidelines for environmental legislation. Due to the fact that the background concentrations strongly depend on geological characteristics such as mineral composition, grain size distribution and organic matter content, several normalization methods have been developed. Empirical (geochemical), theoretical (statistical) and integrated methods (combining both empirical and theoretical methods) are the main approaches described in literature for determination of geochemical background concentrations. In this review paper, the different approaches as well as the main normalization methods for heavy metal concentrations in sediments and soils will be discussed. Both geochemical background concentrations and added risk level (maximum permissible addition) should be taken into account for setting up legal threshold limits. Moreover, different approaches to evaluate the pollution status of heavy metals in sediments and soils, from Sediment/Soil Quality Guidelines to quantitative indices (Geo-accumulation Index-I_geo, Enrichment Factor-EF, Pollution Load Index-PLI and Risk assessment Code-RAC) will be presented. Although guidelines to establish whether a sediment or soil is polluted or not are generally only related to total metal concentrations, the available/reactive pool i.e., availability/reactivity of metals should be taken into account for sediment/soil pollution assessment.     

hOGG1 Ser326Cys Polymorphism and Risk of Hepatocellular Carcinoma among East Asians: A Meta-Analysis

Background

The hOGG1 gene encodes a DNA glycosylase enzyme responsible for DNA repair. The Ser326Cys polymorphism in this gene may influence its repair ability and thus plays a role in carcinogenesis. Several case-control studies have been conducted on this polymorphism and its relationship with the risk of hepatocellular carcinoma (HCC) among East Asians. However, their results are inconsistent.

Methods

We performed a meta-analysis of published case-control studies assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. PubMed, EMBASE, SCI, BIOSIS, CNKI and WanFang databases were searched. A random-effect model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses were conducted for additive, dominant and recessive genetic models.

Results

Eight studies were identified involving 2369 cases and 2442 controls assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. Applying a dominant genetic model, only in the Chinese population, the Cys allele was significantly associated with increased risk of HCC (OR 1.56, 95% CI 1.12–2.17). However, two studies influenced this finding according to sensitivity analysis. Furthermore, considerable heterogeneity and bias existed among Chinese studies.

Conclusion

There is limited evidence to support that the hOGG1 Ser326Cys polymorphism is associated with HCC risk among East Asians. Well-designed and large-sized studies are required to determine this relationship.     

Treatment Outcomes in Undocumented Hispanic Immigrants with HIV Infection

Objective

Little is known about the treatment outcomes of undocumented Hispanic immigrants with HIV infection. We sought to compare the treatment outcomes of undocumented and documented patients 12-months after entering HIV care.

Methods

We conducted a retrospective cohort study of antiretroviral-naive patients 18 years and older attending their first visit at Thomas Street Health Center in Houston, Texas, between 1/1/2003 and 6/30/2008. The study population of 1,620 HIV-infected adults included 186 undocumented Hispanic, 278 documented Hispanic, 986 Black, and 170 White patients. The main outcome measures were retention in care (quarter years with at least one completed HIV primary care provider visit) and HIV suppression (HIV RNA <400 copies/mL), both measured 12-months after entering HIV care.

Results

Undocumented Hispanic patients had lower median initial CD₄ cell count (132 cells/mm³) than documented Hispanic patients (166 cells/mm³; P = 0.186), Black patients (226 cells/mm³; P<0.001), and White patients (264 cells/mm³; P = 0.001). However, once in care, undocumented Hispanic patients did as well or better than their documented counterparts. One year after entering HIV care, undocumented Hispanics achieved similar rates of retention in care and HIV suppression as documented Hispanic and White patients. Of note, black patients were significantly less likely to have optimal retention in care (adjusted odds ratio [aOR] 0.65, CI = 0.45–0.94) or achieve HIV suppression (aOR 0.32, CI = 0.17–0.61) than undocumented Hispanics.

Conclusions

Undocumented Hispanic persons with HIV infection enter care with more advanced disease than documented persons, suggesting testing and/or linkage to care efforts for this difficult-to-reach population need intensification. Once diagnosed, however, undocumented Hispanics have outcomes as good as or better than other racial/ethnic groups. Safety net providers for undocumented immigrants are vital for maintaining individual and public health.     

Design and Selection of a Camelid Single-Chain Antibody Yeast Two-Hybrid Library Produced De Novo for the Cap Protein of Porcine Circovirus Type 2 (PCV2)

Nanobodies (or variable domain of the heavy chain of the heavy-chain antibodies, VHHs) are single-domain antigen-binding fragments derived from camelid heavy chain antibodies. Their comparatively small size, monomeric behavior, high stability, high solubility, and ability to bind epitopes inaccessible to conventional antibodies make them especially suitable for many therapeutic and biotechnological applications. In this paper, for the first time, we created the immunized Camelus Bactrianus VHH yeast two-hybrid (Y2H) library according to the Clontech Mate & Plate library construction system. The transformation efficiency and titer of the VHH Y2H library were 7.26×10⁶ cfu/3 µg and 2×10⁹ cfu/ml, which met the demand for Y2H library screening. Using as an example the porcine circovirus type 2 (PCV2) Cap protein as bait, we screened 21 positive Cap-specific VHH sequences. Among these sequences, 7 of 9 randomly selected clones were strongly positive as indicated by enzyme-linked immunosorbent assay, either using PCV2 viral lysis or purified Cap protein as coated antigen. Additionally, the immunocytochemistry results further indicated that the screened VHHs could specifically detected PCV2 in the infected cells. All this suggests the feasibility of in vivo VHH throughput screening based on Y2H strategy.     

Trends in Population Blood Pressure and Prevalence,Awareness, Treatment,and Control of Hypertension among Middle-Aged and Older Adults in a Rural Area of Northwest China from 1982 to 2010

Objectives

To assess trends in average blood pressure levels and prevalence, awareness, treatment, and control of hypertension among adults in a rural area of Northwest China, and to determine associated risk factors.

Methods

Four cross-sectional population-based surveys were conducted between 1982 and 2010 among randomly selected adults in rural areas of Hanzhong, in Northwest China. Data on blood pressure, body mass index, family history of hypertension, and socio-demographic and lifestyle characteristics were collected in similar way by trained investigators in four surveys. Data of 8575 participants aged 35–64 years was analyzed. Averages and proportions were adjusted for age and sex.

Results

Average blood pressure in the population has increased since 1982 from 76.9 mm Hg to 79.6 mm Hg in 2010 (diastolic) and from 120.9 to 129.7 mm Hg (systolic). Prevalence of hypertension increased from 18.4% in 1982 to 30.5% in 2010, and awareness of hypertension increased from 16.8% to 38.4% in 2010. Treatment of hypertension increased from 1.0% in 1982 to 17.4% in 2010, and control of hypertension increased from 0.1% in 1982 to 3.5% in 2010. All these gradients were statistically significant (P<0.01 for trend). Population blood pressure and prevalence, awareness and treatment of hypertension were positively associated with increasing age, body mass index and having family history of hypertension.

Conclusions

Average blood pressure levels and the prevalence, awareness, treatment and control of hypertension among adults in rural areas of Hanzhong have increased since 1982. However, awareness, treatment and control rates remain low. Public health programs and practical strategies are required to improve prevention and control of hypertension in rural Northwest China. In particular, attention should be given to the elderly and obese, and to those with a family history of hypertension, while raising awareness and treatment among younger adults.     

Tristetraprolin Mediates Radiation-Induced TNF-α Production in Lung Macrophages

The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by macrophages. For in vitro studies we irradiated (4 Gy) either a mouse lung macrophage cell line, MH-S or macrophages isolated from TTP knockout mice, and studied the effects of radiation on TTP and TNF-α levels. To study the in vivo relevance, mouse lungs were irradiated with a single dose (15 Gy) and assessed at varying times for TTP alterations. Irradiation of MH-S cells caused TTP to undergo an inhibitory phosphorylation at Ser-178 and proteasome-mediated degradation, which resulted in increased TNF-α mRNA stabilization and secretion. Similarly, MH-S cells treated with TTP siRNA or macrophages isolated from ttp (−/−) mice had higher basal levels of TNF-α, which was increased minimally after irradiation. Conversely, cells overexpressing TTP mutants defective in undergoing phosphorylation released significantly lower levels of TNF-α. Inhibition of p38, a known kinase for TTP, by either siRNA or a small molecule inhibitor abrogated radiation-induced TNF-α release by MH-S cells. Lung irradiation induced TTP^Ser178 phosphorylation and protein degradation and a simultaneous increase in TNF-α production in C57BL/6 mice starting 24 h post-radiation. In conclusion, irradiation of lung macrophages causes TTP inactivation via p38-mediated phosphorylation and proteasome-mediated degradation, leading to TNF-α production. These findings suggest that agents capable of blocking TTP phosphorylation or stabilizing TTP after irradiation could decrease RILT.     

Identification of a Potent Endothelium-Derived Angiogenic Factor

The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up₄U) from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up₄U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up₄U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up₄U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up₄U after stimulation with shear stress. Mean total plasma Up₄U concentrations of healthy subjects (N = 6) were sufficient to induce angiogenic and proliferative effects (1.34±0.26 nmol L^-1). In conclusion, Up₄U is a novel strong human endothelium-derived angiogenic factor.     

Diversity of Plant Methionine Sulfoxide Reductases B and Evolution of a Form Specific for Free Methionine Sulfoxide

Methionine can be reversibly oxidized to methionine sulfoxide (MetO) under physiological conditions. Organisms evolved two distinct methionine sulfoxide reductase families (MSRA & MSRB) to repair oxidized methionine residues. We found that 5 MSRB genes exist in the soybean genome, including GmMSRB1 and two segmentally duplicated gene pairs (GmMSRB2 and GmMSRB5, GmMSRB3 and GmMSRB4). GmMSRB2 and GmMSRB4 proteins showed MSRB activity toward protein-based MetO with either DTT or thioredoxin (TRX) as reductants, whereas GmMSRB1 was active only with DTT. GmMSRB2 had a typical MSRB mechanism with Cys121 and Cys 68 as catalytic and resolving residues, respectively. Surprisingly, this enzyme also possessed the MSRB activity toward free Met-R-O with kinetic parameters similar to those reported for fRMSR from Escherichia coli, an enzyme specific for free Met-R-O. Overexpression of GmMSRB2 or GmMSRB4 in the yeast cytosol supported the growth of the triple MSRA/MSRB/fRMSR (Δ3MSRs) mutant on MetO and protected cells against H₂O₂-induced stress. Taken together, our data reveal an unexpected diversity of MSRBs in plants and indicate that, in contrast to mammals that cannot reduce free Met-R-O and microorganisms that use fRMSR for this purpose, plants evolved MSRBs for the reduction of both free and protein-based MetO.