关键词：福利；医疗保健；卫生专业人员；少数民族

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Diabetes and mental health conditions co-occur frequently in the United States and each is a risk factor for the other. Moreover, individuals with comorbid diabetes and psychiatric disorders are at greater risk for poor health outcomes than the general population or than their peers with diabetes. One step toward understanding and potentially reducing the health disparities faced by people with comorbid diabetes and mental health conditions is to monitor their receipt of diabetic preventive services, to ensure that these services conform to established standards.

关键词：糖尿病；诊断；健康差距；心理健康

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In postmenopausal women, obesity is associated with a worse breast cancer prognosis, and this may be related to these patients reduced response rate to aromatase inhibitor treatment. Obesity is accompanied by elevated levels of growth factors and inflammatory cytokines that can promote tumorigenesis and regulate the expression and activity of aromatase, the key enzyme in the synthesis of estrogen from androgens. The purpose of this project is to elucidate the role of local aromatase expression and activity in the promotion of breast cancer progression in obese postmenopausal women. Results have demonstrated that serum from obese postmenopausal women stimulates greater aromatase expression in adipose stromal cells (ASC) and MCF-7 breast cancer cells via direct and indirect mechanisms in comparison to serum from normal weight subjects. The obesity-induced aromatase expression in ASC and MCF-7 cells is associated with elevated breast cancer cell estrogen receptor alpha activity in the presence of exogenous testosterone. Further data indicates that the indirect effects of the obese sera on ASC aromatase expression are primarily mediated by inflammatory cytokine-induced prostaglandin E2 production by the cancer cells and macrophages. Based on these findings, future animal and human studies investigating the efficacy of an aromatase inhibitor/COX-2 inhibitor combination treatment in the obese postmenopausal population are being developed.

关键词：芳香；芳香酶抑制剂；乳腺癌细胞（生物学）

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The Health Hazard Evaluation Program received a request from the manager of a federal government office complex. Employees were concerned about health problems including cancer, gallbladder problems, and chronic obstructive pulmonary disease. Some employees believed their health problems were associated with contamination of the buildings, soil, and groundwater from an adjoining weapons component manufacturing agency. The entire complex consisted of 13 buildings with the largest structure at the site containing over 1 million square feet across three floors. This structure contained two main areas: (1) Buildings 1 and 2 (office and warehouse space where most of the complex's employees worked) and (2) the weapons component agency. A floor-to-ceiling fire wall physically separated Buildings 1 and 2 from the weapons component agency. We reviewed environmental sampling records, did a visual inspection of Building 1 and 2 ventilation systems, spoke with employees about their health. We also tested former and current employees with sarcoidosis (an inflammatory disease that is nearly identical to chronic beryllium disease) for sensitization to beryllium, which was used for weapons manufacturing. Our evaluation found (1) no reports of employee overexposures to volatile organic compounds, polychlorinated biphenyls, beryllium or other metals, solvents, formaldehyde, or radon; (2) no evidence of beryllium sensitization among 22 persons tested; and (3) no cancer excess or abnormal pattern of disease. We noted that (1) Buildings 1 and 2 have separate ventilation systems from the weapons component agency and (2) potentially contaminated exhaust air from the weapons component agency was unlikely to enter the outdoor air intake(s) for Building 1 and 2. We recommended the employer encourage employees to learn about their personal cancer risk factors and educate employees on what they can do to reduce their risk for cancer. We also advised the employer to stop all investigations of cancer incidence and routine air and surface wipe sampling for chemicals.

关键词：铍化合物；癌；污染；环境风险；甲醛

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This Synergistic IDEA project seeks to develop a novel strategy to effectively target ErbB2-overexpressing breast cancer with anti-ErbB2 antibody coated nanogels carrying potent chemotherapeutics in combination with HSP90 inhibitors to enhance the endocytosis of ErbB2-receptor bound nanogel cargo. A successful outcome of our studies will provide a new therapeutic approach against a particularly difficult form of breast cancer and may provide a template for therapeutic targeting of other forms of breast cancer and other cancers. Success in preclinical models would also provide strong rationale for clinical translation of this technology with the ultimate goals of selective delivery of imaging and therapeutic modalities to tumors. Robust procedures for the synthesis of nanogels were developed, key structural parameters of block copolymers governing the physicochemical properties of the nanogels were identified, nanogels loaded with combination of anticancer therapeutics and methods for the preparation of ErbB2-targeted nanogels were developed, Mannose functionalized BICs provided a safe and stable platform for gene delivery to macrophages, doxorubicin-nanogels showed an efficient systemic drug delivery to human tumor xenografts.

关键词：乳腺癌；临床医学；药物；单克隆抗体；化疗

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The Health Hazard Evaluation Program received a request from employees at a manufacturer of premolded cable accessories for underground power distribution systems. Employees were concerned about poor ventilation, ergonomic risks, and developing respiratory disease or cancer from exposures during rubber molding, plastic extrusion, soldering, and painting. The plant operated 24 hours a day, 7 days a week with approximately 300 nonunion production employees working 8-hour shifts. Paint department employees normally worked 12-hour shifts.

关键词：染物；电力电缆；环境暴露；人体工程学

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The Health Hazard Evaluation Program received a request from a regional hospital. The employer was concerned about health symptoms (burning and itchy eyes, itchy skin, hair loss, and metallic taste in the mouth) among outpatient cancer and infusion center employees working with or around chemotherapy drugs. The center employed 10 clinical and administrative staff who typically treated about 4 patients per day. During our visit we talked to employees about their work and health concerns; observed how they received, stored, administered, and disposed chemotherapy drugs; took samples from work surfaces to look for chemotherapy drugs; and evaluated the airflow direction in the center and in an isolator cabinet. Additionally, we reviewed workplace injury and illness logs and employee health records, environmental sampling and inspection reports, training documents, and standard operating procedures for handling hazardous drugs. We found low but detectable levels of chemotherapy drugs in surface wipe samples collected throughout the center, including one drug not in use during our visit. During interviews and as recorded by medical surveillance, staff reported mucous membrane irritation, nausea, metallic taste, and intermittent tiredness. Although we cannot definitively link the symptoms to chemotherapy drug exposures, many were consistent with what is reported in the literature and in other settings where chemotherapy drugs are handled. In our interviews, employees reported inconsistent personal protective equipment use. We noted that procedures for handling hazardous drugs did not apply to all personnel who are exposed to chemotherapy drugs and procedures for proper storage, routine housekeeping, medical surveillance, and the hazardous drug list were incomplete. Air from the pharmacy was not being drawn into the pass-through chamber on the isolator cabinet, as employees believed.

关键词：生物效应；癌；化学疗法；药物；环境风险

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In the second year, we continued our work concerning blast- or concussion-induced traumatic brain injury (TBI) that is often associated with tinnitus. In animal studies, we conducted behavioral testing of tinnitus, anxiety and spatial cognition, MRI-DTI and MEMRI imaging, and electrophysiology in the dorsal cochlear nucleus (DCN), inferior colliculus (IC) and auditory cortex (AC), and histological assays. We found that blast-induced tinnitus was accompanied with high anxiety and hyperactivity in the basolateral nuclei of the amygdala, and hypoactivity in the ipsilateral anterior cingulate cortex, along with variable changes in broadband noise-induced responses in the AC, IC and DCN. Blast also caused significant axonal injuries in auditory white matter tracts and enhanced astroglial activity. In addition, we found that concussion induced acute tinnitus and auditory detection deficits, along with axonal injury in the brainstem. In human studies, we conducted audiological, psychophysical, electroacoustic, and neuroimaging studies. Patients with blastinduced tinnitus showed symmetrical hearing thresholds and abnormal DPOAEs, normal middle ear power reflectance, but with increased fractional anisotropy (FA) of DTI data particularly in the corpus callosum and corona radiata and normal SWI in most patients. Patients with concussions had unpredictable hearing loss with large variability and asymmetric power reflectance values. While patients with blast + concussioninduced had less hearing loss than those with blast or concussion alone, tinnitus loudness was greatest for patients with blast + concussion, least for blast alone, with concussion alone having intermediate loudness.

关键词：中耳；创伤性脑损伤；听觉缺陷；电生理学

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Docetaxel (DTX), a semi-synthetic analog of paclitaxel, has emerged as the standard of care for chemotherapy of hormone-resistant prostate cancer. Docetaxel confers its anti-neoplastic activity by inhibiting microtubule depolymerization, which leads to G2/M mitotic arrest and subsequent apoptosis (1). However, most patients treated with DTX ultimately develop resistance to the drug and succumb to the disease (2). Therefore, understanding the mechanisms underlying DTX resistance is a priority area in prostate cancer research. Previously, it was reported that CXCL12/CXCR4 signaling play an important role in microtubule organization in immune cells (3) and its inhibition induced mitotic catastrophe (G2/M arrest) in ovarian cancer cells (4). Based on these earlier observations, we hypothesized that CXCL12-CXCR4 signaling axis would promote docetaxel resistance by counteracting the microtubule stabilizing action of docetaxel.

关键词：前列腺癌；凋亡；化疗；有丝分裂

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The goal of this project is to analyze the entire microbial population of the mucosa in the upper gastrointestinal tract of children with autism to determine if there is an overgrowth of specific populations of bacteria and analyze the relationship between the intestinal flora and behavior. Our current sub-contractor from the institute of Genome Sciences, University of Maryland School of Medicine was not able to amplify and sequence DNA from the duodenal biopsies of autistic children and controls. A new sub-contractor the Research and Testing Laboratory was found. A new set of duodenal biopsies from children with and without autism will be sent to the Research and Testing Laboratory for DNA extraction, PCR for 16S rRNA, sequencing. No additional funding will be requested to complete this project.

关键词：胃肠道系统；精神障碍；活组织检查

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