NTO was administered to male (0, 250, and 500 mg/kg-day) and female (0, 500, and 1000 mg/kg-day) Sprague-Dawley rats (15/sex/group) via oral gavage from weaning through puberty. Animals were examined daily for onset of puberty. Estrous cyclicity was evaluated daily upon completion of vaginal opening (VO). Age and body weight at VO and PPS, and all measures of estrous cyclicity were not affected by treatment with NTO. Testis mass was reduced by 30% and 65% compared to control in the 250 and 500 mg/kg-day groups, respectively. The reduction in testis mass was associated with tubular degeneration/atrophy. Less pronounced reductions in the mass of androgen-dependent accessory reproductive tissues were also observed in the 500 mg/kg-day group; however, the reduction was only significant in the epididymides. There were no differences in hormone levels or thyroid follicle and colloid scores between NTO treatment groups and the control groups. These findings suggest that NTO is not acting as an estrogen or thyroid active compound, but may indicate effects on steroidogenesis and/or direct testicular toxicity.

关键词：雌激素；曝光（生理学）；激素;大鼠

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Superparamagnetic iron oxide nanoparticle (SPION) has attracted a great deal of attention in the fields of medicine and biology due to its non-toxicity, large specific surface area, amenability to various surface fuctionalization, and unique magnetic properties. For biomedical applications, we synthesized two kinds of SPIONs by co-precipitation and polyol methods, designated as C- and P-SPIONs, respectively. To increase their solubility and stability in an aqueous solution, both of the SPIONs were functionalized with hyperbranched polyglycerol (PG) through ring-opening polymerization of glycidol. Scanning transmission electron microscopy (STEM) and dynamic light scattering (DLS) measurements revealed that the P-SPION provided individual nanoparticles without aggregation after the PG fuctionalization. This P-SPION-PG was highly soluble not only in pure water (＞ 40 mg/mL), but also in a phosphate buffer solution (＞ 25 mg/mL). Such high solubility enabled separation of P-SPION-PG according to their size by size exclusion chromatography (SEC). The size-separated P-SPION-PG shows a gradual increase in transverse relaxivity (r_2) with increasing particle size. The hydroxyl group in PG also serves as a scaffold for further surface functionalization. For targeted cell labeling, we functionalized P-SPION-PG through multi-step organic transformations (-OH → -OTs (tosylate) → -N_3 → -RGD) including click chemistry as a key step to impart targeting specificity by immobilization of cyclic RGD peptide on the surface. The targeting effect was demonstrated by the cell experiments; P-SPION-PG-RGD was taken up by the cells overexpressing α_vP_3-integrin such as U87MG and A549. In addition, near-infrared (NIR) fluorescence dye (IRdye 800CW) was immobilized on the surface of P-SPION-PG through amide linkage. The resulting P-SPION-PG-IRdye showed good solubility in phosphate buffered saline (PBS) and strong fluorescence in NIR region, which may find application in optical/MR bimodal imaging.

关键词：氧化铁；纳米颗粒；聚甘油

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The application of proanthocyanidins (PACs) to the capture and removal of bacterial lipopolysaccharide (LPS) from solution has been demonstrated. PACs from whole cranberries, grape juice, black tea, and cranberry juice were purified and immobilized onto thiol-activated Sepharose beads. This material was used in pull-down type assays for the capture of LPS. The binding of LPS by PACs has been shown to compete with that of polymyxin B, which is known to bind the lipid A component of LPS. The removal of LPS from solution using a column of a PAC modified resin is also demonstrated over a range of pH values and ionic strengths. The performance of the resin in protein solutions as compared to that of polymyxin B is evaluated. PACs were also immobilized onto Luminex beads and applied to the capture of E. coli and B. globigii.

关键词：细菌性疾病；采集；儿茶素；内毒素树脂

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Previous studies have shown that MDSC block adaptive anti-tumor immunity by producing high levels of oxidizing agents such as reactive oxygen species (ROS), nitric oxide (NO), and peroxynitrite. Despite high levels of the toxic oxidizing agents, MDSC survive and suppress anti-tumor immunity. We hypothesize that MDSC survival is mediated by the antioxidant-regulating transcription factor Nrf2. To test this hypothesis, wild type and Nrf2-/- BALB/c and C57BL/6 mice were injected with 4T1 mammary carcinoma cells or MC38 colon carcinoma cells, respectively. Tumor-bearing mice were assayed weekly for percentage of MDSC in the blood and for MDSC levels of ROS and glutathione, MDSC production of H2O2 and suppressive activity, and MDSC apoptosis. Mice were also followed for survival. Nrf2-/- MDSC had more ROS and less glutathione than wild type MDSC, indicating that Nrf2-/- MDSC were more oxidatively stressed. Nrf2-/- MDSC were more apoptotic than wild type MDSC. Nrf2-/- and wild type mice had similar rates of primary tumor growth and MDSC accumulation, but tumor- bearing Nrf2-/- mice lived longer, indicating that Nrf2 contributes to tumor progression. Nrf2-/- MDSC produce less H2O2 and were less suppressive than wild type MDSC. These data are consistent with our hypothesis that Nrf2 regulates MDSC survival and suppressive activity, resulting in less suppressive MDSC in Nrf2-/- mice, thereby increasing anti-tumor immunity against metastatic disease.

关键词：乳腺癌；肿瘤；一氧化氮

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The human acetylcholinesterase (hAChE) gene was cloned into the pHLsec expression vector. The recombinant enzyme (rhAChEmD) was expressed on a large scale in adherent 293T cells. It was secreted as a monomeric species, purified by affinity chromatography, and deglycosylated with PNGase F. A crystallization screen, using the Mosquito crystallization robot, identified conditions for formation of diffraction-quality crystals, in 0.025% dichloromethane/12% PEG 20,000/0.1M imidazole, pH7.0. The crystals formed in the hexagonal space group P3112, with cell constants a=125.31, b=125.31, c=131.40 , and one monomer per asymmetric unit. A complete dataset, to 2.9 resolution, was collected at 100 K at the ESRF (Grenoble, France). The structure was solved by molecular replacement, resulting in an Rfree of 23.74%, and Rwork of 19.31%, for all data to 2.9 . The coordinates and structures factors have been deposited in the PDB, with IDcode 4PQE. As an initial step for synthesis of a GF surrogate, the chloridate, CH3P(O)(O-cyclohexyl)Cl, has been prepared, and will be reacted with coumarin. Conditions have also been developed for expression of a full-length rhAChE construct, rhAChET that assembles to form the physiological tetramer.

关键词：乙酰胆碱酯酶；基因；单体；神经毒剂

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The Health Hazard Evaluation (HHE) Program received a request on behalf of a state correctional and rehabilitation agency and a state correctional health care services agency concerning potential employee exposure to the fungus Coccidioides at two state prisons in California. Coccidioidomycosis, also known as valley fever, is a disease caused by inhalation of spores of a fungus of the Coccidioides species, which grows in the soil in semiarid areas. The prisons are located in counties where the disease is considered hyperendemic. At the time of our evaluation in 2013, staff numbered over 1,300 in prison A and 1,500 in prison B. NIOSH investigators reviewed work and occupational health policies and practices, reviewed medical and work information for the coccidioidomycosis cases among prison employees, interviewed a convenience sample of 172 prison employees about their work practices and exposures, and looked at the ventilation systems in buildings where more employees worked such as clinics and offices and some inmate housing units. We identified 103 confirmed cases of coccidioidomycosis among prison employees over a 4 1/2-year period (January 2009-June 2013). The crude average annual incidence was 1,039 cases per 100,000 employees for prison A and 511 cases per 100,000 employees for prison B over this time. However, we do not know if each confirmed case of coccidioidomycosis among prison employees was due to an exposure at work or outside of work. Interviews with employees revealed that they may be potentially exposed to Coccidioides in the outdoor work environment through soil disruption activities, being present during dust storms, and other outdoor activities. Employees may also be potentially exposed to Coccidioides during outdoor activities outside of work. Neither the written respiratory protection plans nor the aerosol transmissible diseases exposure control plans specifically discuss exposure to Coccidioides. Most of the offices and clinics were air-conditioned, temperature and relative humidity measurements were within established guidelines, and an adequate amount of outdoor air was being provided. However, some prison areas had airflow patterns that could result in entrainment of unconditioned outdoor air. Environmental control measures such as wetting soil before it is disturbed, maintaining grass on exercise yards, stabilizing soil, paving roads, improving building ventilation, and changing work practices (such as reducing time spent outdoors) would be expected to reduce dust exposures to varying degrees. However, none of these measures will eliminate exposure to Coccidioides, and their relative effectiveness in reducing occupational coccidioidomycosis is unknown.

关键词：健康危害评估；职业安全与健康；职业暴露

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The objectives of this proposed study are to: (1) Coordinate medical care to meet the physical and mental health needs of OIF/OEF veterans with injuries incurred in combat; (2) Determine the immediate and sustained effects of telerehabilitation on patient outcomes on a variety of physical, psychological and social functions over the period of study; (3) Examine the perceived benefits and limitations of the telerehab from the veteran and caregiver perspectives and; (4) Evaluate the effectiveness of telerehab on health outcomes and resource utilization. Study design: This 3 year study will use a prospective observational design to extend the present study at the Tampa VA to recruit 60 veterans each at the Tampa and Miami VA hospitals divided equally among the two groups receiving telerehab and those with traditional care acting as controls at each site. Methods: We will utilize qualitative and quantitative analysis for evaluating changes in functional and mental health status, community participation, VA healthcare utilization, and veteran/family perceptions of telerehab.

关键词：卫生；医院；医疗服务；心理健康；患者

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Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease. Epstein-Barr virus (EBV) infection is associated with MS pathogenesis. However, mechanism for the EBV-MS connection is unclear. The blood brain barrier (BBB) is a separation of circulating blood and the brain extracellular fluid in the central nervous system. BBB contains both endothelial cells as well as astrocytes. Interestingly EBV is able to infect both kinds of cells. Because EBV is able to transfer infection from one cell type to another cell type, it is thus hypothesized that EBV uses endothelial cells to infect astrocytes in the BBB, generate serials of cytokines that may eventually cause a leakage in the BBB. An in vitro model for human BBB will be established and infected the endothelial side of the BBB with EBV. Whether BBB is infected by the virus, the expression profiles of cytokines and other cellular genes, as well as the integrity of the BBB will be determined. Because both cytokine production and leakage of BBB are critical events for MS, this line of experiments may provide an evidence to support the etiological role of EBV in MS disease.

关键词：自身免疫性疾病；血脑屏障细胞（生物学）；医药

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Human adenoviruses of species B, C, and E (HAdV-B, C, -E) are frequent causative agents of acute respiratory infections worldwide. As part of a surveillance program aimed at identifying the etiology of influenza-like illness (ILI) in Egypt, we characterized 105 adenovirus isolates from clinical samples collected between 2003 and 2010. Identification of the isolates as HAdV was accomplished by an immunofluorescence assay (IFA) and confirmed by a set of species and type specific polymerase chain reactions (PCR). Of the 105 isolates, 42% were identified as belonging to HAdV-B, 60% as HAdV C, and 1% as HAdV-E. We identified a total of six co-infections by PCR, of which five were HAdV-B/HAdV- C co-infections, and one was a co-infection of two HAdV-C types: HAdV-5/HAdV-6. Molecular typing by PCR enabled the identification of eight genotypes of human adenoviruses; HAdV-3 (n = 22), HAdV-7 (n = 14), HAdV-11 (n = 8), HAdV-1 (n = 22), HAdV-2 (20), HAdV-5 (n = 15), HAdV-6 (n = 3) and HAdV-4 (n = 1). The most abundant species in the characterized collection of isolates was HAdV-C, which is concordant with existing data for worldwide epidemiology of HAdV respiratory infections. We identified three species, HAdV-B, -C and -E, among patients with ILI over the course of 7 years in Egypt, with at least eight diverse types circulating.

关键词：病毒；年龄组；含量测定；链式反应；脱氧核糖核酸

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Clinical trials are crucial to determining the safety of medical interventions and their ability to achieve particular health outcomes. Clinical trials are required by regulatory authorities around the world before a new medical product can be brought to market, or before a new indication, formulation, or target population can be approved for an intervention already on the market (ICH, 1995). After a products introduction, additional clinical trials are commonly conducted by industry, government, and academia to further define the relative safety and efficacy (or effectiveness) of the product. Clinical trials are also used to study interventions that do not involve regulated medical products, for example, surgical techniques, behavioral interventions, or studies designed to improve disease management practice (Califf, 2013). Vast amounts of data are generated over the course of a clinical trial. These data are held by the sponsors conducting the clinical trial, and in some instances, by participants or their advocates (Drazen, 2002; Terry and Terry, 2011). Depending on the regulatory jurisdiction, data might or might not be shared or made available to the public for secondary uses. Shared data might include both summary data and individual patient data. In the United States, if a sponsor is seeking regulatory approval, data are shared in confidence with regulators. Select study data might also be made available to individual researchers on a case by case basis upon request, or could be made publicly available, usually at the summary level, for example, through publication in a peer-reviewed journal or through publicly accessible clinical trial registration sites.

关键词：临床试验；数据共享；医疗措施

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