Exposure to PM2.5 and Blood Lead Level in Two Populations in Ulaanbaatar, Mongolia

Approximately 60% of the households in Ulaanbaatar live in gers (a traditional Mongolian dwelling) in districts outside the legal limits of the city, without access to basic infrastructure, such as water, sewage systems, central heating, and paved roads, in contrast to apartment residents. This stark difference in living conditions creates different public health challenges for Ulaanbaatar residents. Through this research study we aim to test our hypothesis that women living in gers burning coal in traditional stoves for cooking and heating during the winter are exposed to higher concentrations of airborne PM2.5 than women living in apartments in Ulaanbaatar, Mongolia, and this exposure may include exposures to lead in coal with effects on blood lead levels. This cross sectional study recruited a total of 50 women, 40–60 years of age, from these two settings. Air sampling was carried out during peak cooking and heating times, 5:00 p.m.–11:00 p.m., using a direct-reading instrument (TSI SidePak™) and integrated polytetrafluoroethylene (PTFE) filters using the SKC Personal Environmental Monitor. Blood lead level (BLL) was measured using a LeadCare II rapid field test method. In our study population, measured PM2.5 geometric mean (GM) concentrations using the SidePak™ in the apartment group was 31.5 (95% CI:17–99) μg/m3, and 100 (95% CI: 67–187) μg/m3 in ger households (p < 0.001). The GM integrated gravimetric PM2.5 concentrations in the apartment group were 52.8 (95% CI: 39–297) μg/m3 and 127.8 (95% CI: 86–190) μg/m3 in ger households (p = 0.004). The correlation coefficient for the SidePak™ PM2.5 concentrations and filter based PM2.5 concentrations was r = 0.72 (p < 0.001). Blood Lead Levels were not statistically significant different between apartment residents and ger residents (p = 0.15). The BLL is statistically significant different (p = 0.01) when stratified by length of exposures outside of the home. This statistically significant difference in increased BLL could be due to occupational or frequent exposure to other sources of indoor or outdoor air pollution that were not measured. Blood lead levels from our study population are the  study measurements published on women aged 40–60 years of age in Mongoli

Assessment of blood lead levels and associated risk factors among children In Ulaanbaatar, Mongolia

Objectives: The objectives of this study were to determine BLLs with a LeadCare II analyzer in children living in Ulaanbaatar, Mongolia and to identify potential risk factors influencing their BLLs with a lifestyle and residential environment questionnaire. Methods: A total of 153 children aged 6-8 years old were tested in 2014. Results: The geometric mean BLL was 5.3 µg/dL (95% CI: 4.9 – 5.7 µg/dL) and 69.3% of the children had blood lead levels ≥5 μg/dL (the United States Centers for Disease Control and Prevention’s current reference level). Factors that were significant (p<0.05) predictors of BLL in a multiple linear regression model were sex, age, father’s education level, and father’s job type. The BLL from this study in 2014 shows a 60% decrease since a prior 2005 study, likely due to the ban on leaded gasoline in the country. Conclusion: Academic performance was significantly influenced by BLL, indicating that actions still need to be taken to reduce lead exposure in Ulaanbaatar

Reducing AD-Like Pathology in 3xTg-AD Mouse Model by DNA Epitope Vaccine — A Novel Immunotherapeutic Strategy

BACKGROUND: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42) (Abeta(1-11)) , a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype. METHODS AND FINDINGS: We generated pMDC-3Abeta(1-11)-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. CONCLUSIONS: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials

Regulatory B cells in pregnancy: lessons from autoimmunity, graft tolerance, and cancer

The success of pregnancy is contingent on the maternal immune system recognizing and accommodating a growing semi-allogeneic fetus. Specialized subsets of lymphocytes capable of negative regulation are fundamental in this process, and include the regulatory T cells (Tregs) and potentially, regulatory B cells (Bregs). Most of our current understanding of the immune regulatory role of Bregs comes from studies in the fields of autoimmunity, transplantation tolerance, and cancer biology. Bregs control autoimmune diseases and can elicit graft tolerance by inhibiting the differentiation of effector T cells and dendritic cells (DCs), and activating Tregs. Furthermore, in cancer, Bregs are hijacked by neoplastic cells to promote tumorigenesis. Pregnancy therefore represents a condition that reconciles these fields-mechanisms must be in place to ensure maternal immunological tolerance throughout gravidity to allow the semi-allogeneic fetus to grow within. Thus, the mechanisms underlying Breg activities in autoimmune diseases, transplantation tolerance, and cancer may take place during pregnancy as well. In this review, we discuss the potential role of Bregs as guardians of pregnancy and propose an endocrine-modulated feedback loop highlighting the Breg-Treg-tolerogenic DC interface essential for the induction of maternal immune tolerance.Ruth Marian Guzman-Genuino and Kerrilyn R. Diene

The Role of Regulatory T Cells in Cancer

There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is a clear rationale for developing clinical strategies to diminish their regulatory influences, with the ultimate goal of augmenting antitimor immunity. Therefore, manipulation of Treg cells represent new strategies for cancer treatment. In this Review, I will summarize and review the explosive recent studies demonstrating that Treg cells are increased in patients with malignancies and restoration of antitumor immunity in mice and humans by depletion or reduction of Treg cells. In addition, I will discuss both the prognostic value of Treg cells in tumor progression in tumor-bearing hosts and the rationale for strategies for therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs and microRNA

B cell regulation of the anti-tumor response and role in carcinogenesis

The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate the immune response to malignant cells. Accumulating evidence is pointing to a role for B cells in modulating the immune response to both solid tumors and hematologic cancer. Evidence from murine autoimmune models has defined B regulatory cell (Breg) subsets that express cytokines such as IL-10, TGF-β, and/or express immune regulatory ligands such as PD-L1, which can suppress T cell and/or natural killer cell responses. Multiple murine tumor models exhibit decreased tumor growth in B cell deficient or B cell depleted mice. In several of these models, B cells inhibit T cell mediated tumor immunity and/or facilitate conversion of T cells to CD4(+)CD25(+)FoxP3(+) T regs, which act to attenuate the innate and/or adaptive antitumor immune response. Mechanisms of suppression include the acquisition of inhibitory ligand expression, and phosphorylation of Stat3, and induction of IL-10 and TGF-β, resulting in a Breg phenotype. Breg suppressive activity may affect diverse cell subtypes, including T effector cells, NK cells, myeloid derived suppressor cells (MDSC) and/or tumor associated macrophages. B cells may also directly promote tumorigenesis through recruitment of inflammatory cells, and upregulation of pro-angiogenic genes and pro-metastatic collagenases. Breg infiltration has now been identified in a variety of solid tumor malignancies including but not limited to ovarian, gastric, non-small cell lung cancer, pancreatic, esophageal, head and neck, and hepatocellular carcinomas. Increasing evidence suggests that recruitment of B cells and acquisition of suppressive activity within the tumor bed may be an important mechanism through which B cells may modulate innate and/or adaptive anti-tumor immunity. B cell depletion in the clinic using anti-CD20 antibodies and/or inhibitors of BTK and/or other signaling pathways, may be a useful strategy for augmenting the anti-tumor immune response