Diet Influences Expression of Autoimmune‐Associated Genes and Disease Severity by Epigenetic Mechanisms in a Transgenic Mouse Model of Lupus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98819/1/art37967.pd

Lipid-soluble Vitamins A, D, and E in HIV-Infected Pregnant women in Tanzania.

There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions

Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer

Recent studies have linked expression of lectin-like ox-LDL receptor 1 (OLR1) to tumorigenesis. We analyzed microarray data from Olr1 knockout (KO) and wild type (WT) mice for genes involved in cellular transformation and evaluated effects of OLR1 over-expression in normal mammary epithelial cells (MCF10A) and breast cancer cells (HCC1143) in terms of gene expression, migration, adhesion and transendothelial migration. Twenty-six out of 238 genes were inhibited in tissues of OLR1 KO mice; the vast majority of OLR1 sensitive genes contained NF-κB binding sites in their promoters. Further studies revealed broad inhibition of NF-kB target genes outside of the transformation-associated gene pool, with enrichment themes of defense response, immune response, apoptosis, proliferation, and wound healing. Transcriptome of Olr1 KO mice also revealed inhibition of de novo lipogenesis, rate-limiting enzymes fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd1) and ELOVL family member 6 (Elovl6), as well as lipolytic phospholipase A2 group IVB (Pla2g4b). In studies comparing MCF10A and HCC1143, the latter displayed 60% higher OLR1 expression. Forced over-expression of OLR1 resulted in upregulation of NF-κB (p65) and its target pro-oncogenes involved in inhibition of apoptosis (BCL2, BCL2A1, TNFAIP3) and regulation of cell cycle (CCND2) in both cell lines. Basal expression of FASN, SCD1 and PLA2G4B, as well as lipogenesis transcription factors PPARA, SREBF2 and CREM, was higher in HCC1143 cells. Over-expression of OLR1 in HCC1143 cells also enhanced cell migration, without affecting their adherence to TNFα-activated endothelium or transendothelial migration. On the other hand, OLR1 neutralizing antibody inhibited both adhesion and transmigration of untreated HCC1143 cells. We conclude that OLR1 may act as an oncogene by activation of NF-kB target genes responsible for proliferation, migration and inhibition of apoptosis and de novo lipogenesis genes

Structural Stability Analysis of Waste Packages Containing Low- and Intermediate-Level Radioactive Waste in a Silo-type Repository

The structural stability of a waste package is essential for containing radioactive waste for the long term in a repository. A silo-type disposal facility would require more severe verification for the structural integrity, because of radioactive waste packages staked with several tens of meters and overburdens of crushed rocks and shotcretes. In this study, structural safety was analyzed for a silo-type repository, located approximately 100 m below sea level in Gyeongju, Korea. Finite element simulation was per -formed to investigate the influence of the loads from the backfilling materials and waste package stacks on the mechanical stress of the disposed of wastes and containers. It was identified that the current design of the waste package and the compressive strength criterion for the solidified waste would not be enough to maintain structural stability. Therefore, an enhanced criterion for the compressive strength of the solidified waste and several reinforced structural designs for the disposal concrete container were proposed to prevent failure of the waste package based on the results of parametric studies

Oral Health Status, Knowledge, and Practices in an Amish Population

This study was conducted in the summer of 1985 to assess the oral health status, knowledge, and practices of an Amish population in southwest Michigan. Dental caries experience, periodontal health, and oral hygiene status were recorded using decayed, missing, and filled surfaces (DMFS), periodontal index (PI), and simplified oral hygiene index (OHI-S). Data on oral health knowledge and practices were collected by interviews using a structured questionnaire. Results showed significantly lower levels of disease among Amish. DMFS scores for 5–17-year-old Amish children were almost half that of the US general population (NIDR 1979–80). PI score of all ages combined was 2.0, which was 3.6 times lower than a national sample (1971–74). Lower levels of disease in Amish could be related to their way of life and dietary patterns. A relatively higher level of unmet need for prosthodontic care, inadequate oral health knowledge, and barriers to dental care in the study population emphasize the need for dental public health and health education programs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65488/1/j.1752-7325.1988.tb03184.x.pd

Report on a single‐topic conference on “Chronic Viral Hepatitis–Strategies to Improve Effectiveness of Screening and Treatment”

The 2010 Institute of Medicine report on “Hepatitis and Liver Cancer” indicated that lack of knowledge and awareness about chronic hepatitis B (HBV) and C virus (HCV) infections and insufficient understanding about the extent and seriousness of this public health problem impeded current efforts to prevent and control hepatitis B and C. A single‐topic conference was held in June 2011 to discuss strategies to improve the effectiveness of screening, care referral, and clinical management of chronic HBV and HCV infections with the ultimate goal of reducing morbidity and mortality from these infections. Various models that have been shown to improve hepatitis screening and effectiveness of hepatitis treatment in the community, including rural settings and populations that have traditionally been excluded due to comorbidities, were presented. Recent advances in laboratory testing, medical management, and new antiviral therapies will not decrease the burden of viral hepatitis if persons at risk for or who are living with viral hepatitis are not aware of the risks, have not been diagnosed, or have no access to care. Systematic changes in our health care delivery system and enhanced coordination of prevention and care services with partnerships between public health leaders and clinicians through education of the public and health care providers and linkage of infected persons with care and treatment services can increase the success of preventing viral hepatitis and the effectiveness of hepatitis treatment in the real world. Implementation of these changes is feasible and will require policy changes, coordination among government agencies, and collaboration between government agencies, health care providers, community organizations, and advocacy groups. (H EPATOLOGY 2012;55:307–315)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89489/1/24797_ftp.pd

A long view of liberal peace and its crisis

The ‘crisis’ of liberal peace has generated considerable debate in International Relations. However, analysis is inhibited by a shared set of spatial, cultural and temporal assumptions that rest on and reproduce a problematic separation between self-evident ‘liberal’ and ‘non-liberal’ worlds, and locates the crisis in presentist terms of the latter’s resistance to the former’s expansion. By contrast, this article argues that efforts to advance liberal rule have always been interwoven with processes of alternative order-making, and in this way are actively integral, not external, to the generation of the subjectivities, contestations, violence and rival social orders that are then apprehended as self-evident obstacles and threats to liberal peace and as characteristic of its periphery. Making visible these intimate relations of co-constitution elided by representations of liberal peace and its crisis requires a long view and an analytical frame that encompasses both liberalism and its others in the world. The argument is developed using a Foucauldian governmentality framework and illustrated with reference to Sri Lanka

Vitamin D and HIV Progression among Tanzanian Adults Initiating Antiretroviral Therapy

Background: There is growing evidence of an association between low vitamin D and HIV disease progression; however, no prospective studies have been conducted among adults receiving antiretroviral therapy (ART) in sub-Saharan Africa. Methods Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed at ART initiation for a randomly selected cohort of HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania during 2006–2010. Participants were prospectively followed at monthly clinic visits for a median of 20.6 months. CD4 T-cell measurements were obtained every 4 months. Proportional hazard models were utilized for mortality analyses while generalized estimating equations were used for CD4 T-cell counts. Results: Serum 25(OH)D was measured in 1103 adults 9.2% were classified as vitamin D deficient (30 ng/mL). After multivariate adjustment, vitamin D deficiency was significantly associated with increased mortality as compared to vitamin D sufficiency (HR: 2.00; 95% CI: 1.19–3.37; p = 0.009), whereas no significant association was found for vitamin D insufficiency (HR: 1.24; 95% CI: 0.87–1.78; p = 0.24). No effect modification by ART regimen or change in the associations over time was detected. Vitamin D status was not associated with change in CD4 T-cell count after ART initiation. Conclusions: Deficient vitamin D levels may lead to increased mortality in individuals receiving ART and this relationship does not appear to be due to impaired CD4 T-cell reconstitution. Randomized controlled trials are needed to determine the safety and efficacy of vitamin D supplementation for individuals receiving ART

Treating cofactors can reverse the expansion of a primary disease epidemic

<p>Abstract</p> <p>Background</p> <p>Cofactors, "nuisance" conditions or pathogens that affect the spread of a primary disease, are likely to be the norm rather than the exception in disease dynamics. Here we present a "simplest possible" demographic model that incorporates two distinct effects of cofactors: that on the transmission of the primary disease from an infected host bearing the cofactor, and that on the acquisition of the primary disease by an individual that is not infected with the primary disease but carries the cofactor.</p> <p>Methods</p> <p>We constructed and analyzed a four-patch compartment model that accommodates a cofactor. We applied the model to HIV spread in the presence of the causal agent of genital schistosomiasis, <it>Schistosoma hematobium</it>, a pathogen commonly co-occurring with HIV in sub-Saharan Africa.</p> <p>Results</p> <p>We found that cofactors can have a range of effects on primary disease dynamics, including shifting the primary disease from non-endemic to endemic, increasing the prevalence of the primary disease, and reversing demographic growth when the host population bears only the primary disease to demographic decline. We show that under parameter values based on the biology of the HIV/<it>S. haematobium </it>system, reduction of the schistosome-bearing subpopulations (e.g. through periodic use of antihelminths) can slow and even reverse the spread of HIV through the host population.</p> <p>Conclusions</p> <p>Typical single-disease models provide estimates of future conditions and guidance for direct intervention efforts relating only to the modeled primary disease. Our results suggest that, in circumstances under which a cofactor affects the disease dynamics, the most effective intervention effort might not be one focused on direct treatment of the primary disease alone. The cofactor model presented here can be used to estimate the impact of the cofactor in a particular disease/cofactor system without requiring the development of a more complicated model which incorporates many other specific aspects of the chosen disease/cofactor pair. Simulation results for the HIV/<it>S. haematobium </it>system have profound implications for disease management in developing areas, in that they provide evidence that in some cases treating cofactors may be the most successful and cost-effective way to slow the spread of primary diseases.</p