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OBJECTIVE Investigate the following in rescue and cleanup workers exposed to the World Trade Center (WTC) disaster 17 years post-fallout: (1) allergic hypersensitivity; (2) spirometry; (3) impulse oscillometry; and (4) the reversibility of airway hyperresponsiveness and distal airways narrowing pre- and post-bronchodilator. METHODS In subjects (n = 54) referred to our clinic from the WTC Health Program for management of allergy-immunology services, environmental allergy testing, impulse oscillometry (IOS), and spirometry results were retrospectively reviewed to determine the long-term impact of exposure to the WTC fallout. RESULTS Rescue and cleanup workers exposed to the WTC fallout had a high incidence of allergic hypersensitivity and had evidence of permanent small airways dysfunction characterized by distal airways narrowing and airway hyperresponsiveness. CONCLUSION Following exposure to the WTC disaster, the patients in our cohort developed allergic hypersensitivity and severe lung injury with only partial reversibility.

Patients on immunosuppressant agents, including oral corticosteroids, are susceptible to fungal colonization despite being otherwise immunologically intact. This case report highlights a state-of-the-art biological modifier therapy for the complex care of a patient with refractory occupational asthma, allergic rhinitis, and mixed fungal colonization. A dyspneic 38-year-old male janitor with steroid-dependent occupational asthma refractory to omalizumab therapy was colonized with Candida and Alternaria following a promotion to a managerial position in a moldy office. He was treated with itraconazole and systemic steroids. Pulmonary workup revealed moderate obstructive ventilatory defect, peripheral airway hyperresponsiveness, and eosinophilic airway inflammation. Three additional biological modifiers (reslizumab, benralizumab, and dupilumab) were administered to this patient. His asthma was ultimately controlled with reslizumab and dupilumab. Fractional exhaled nitric oxide (FeNO) normalized after dupilumab monotherapy, enabling the patient to taper off chronic prednisone therapy. Various occupational exposures are crucial epidemiologic factors related to infection and go hand-in-glove with long-term prednisone treatment towards increasing susceptibility to fungal colonization. Steroid-sparing anti-interleukin-5 (IL-5) agents and dupilumab should be considered as alternative treatment options for patients, such as ours, with eosinophilic, prednisone-dependent asthma refractory to omalizumab therapy.

(BACKGROUND): Military personnel post-deployment to Iraq and Afghanistan have noted new-onset respiratory illness. This study’s primary objective was to further develop an animal model of Iraq Afghanistan War Lung Injury (IAW-LI) and to test a novel class of anti-injury drug called RuX. (METHODS): Particulate Matter (PM) samples were obtained in Iraq then characterized by spectromicroscopy. C57BL/6 mice underwent orotracheal instillation with PM, followed by drinkable treatment with RuX. Lung histology, inspiratory capacity (FlexiVent), thymic/splenic regulatory T cell (Treg) number, and whole-lung genomics were analyzed. (RESULTS): Tracheal instillation of Iraq PM led to lung septate thickening and lymphocytic inflammation. PM-exposed mice had suppression of thymic/splenic regulatory T-cells (Tregs). Drinking RuX after PM exposure attenuated the histologic lung injury response, improved lung inspiratory capacity, and increased Tregs. Pooled whole lung genomics suggest differences among gene expression of IL-15 among control, PM, and PM+RuX groups. (CONCLUSIONS): RuX, a ruthenium and alpha-lipoic acid complex, attenuates lung injury by improving histology and inspiratory capacity via upregulation of Tregs in Iraq PM-exposed C57BL/6. Plausible genomic effects may involve IL=15 whole lung gene expression.

When Dr. Szema asked me to talk to a psychiatric patient, I was nervous and shocked. I was afraid of being uncomfortable while staying with her. How do I to talk to her? How do I to start the conversation? What if she stared at me without saying a word? We were asked to see the patient because of recurrent septic shock, and the patient had already been admitted to the hospital three times before we saw her. Although she got a lot of fluid, her blood pressure was still low. As a result, the intensive care unit team was worried that she may be immunocompromised. Nevertheless, based on her medical records, behaviors, and information we gathered from her surrounding people in the hospital, Dr. Szema believed she had Munchausen’s syndrome. I researched scientific articles in preparation. I left Dr. Szema’s office and anxiously checked my watch for the rest of the day (Fig. 7.1).

Aerobic exercise is known to influence brain function, e.g., enhancing executive function in both children and adults, with many of these influences being attributed to alterations in neurogenesis and neuronal function. Yet oligodendroglia in adult brains have also been reported to be highly responsive to exercise, including in the prefrontal cortex (PFC), a late myelinating region implicated in working memory. However, whether exercise affects oligodendroglia or myelination in juveniles, either in the PFC or in other brain regions, remains unknown. To address this, both juvenile and young adult mice were provided free access to running wheels for four weeks followed by an analysis of oligodendrocyte development and myelination in the PFC and the corpus callosum, a major white matter tract. Working memory and PFC NG2+ cell development were both affected by exercise in juvenile mice, yet surprisingly these exercise-mediated effects were distinct in juveniles and young adults. In the PFC, NG2+ cell proliferation was increased in exercising juveniles, but not young adults, whereas newly-born oligodendrocyte production was increased in exercising young adults, but not juveniles. Although no overall changes in myelin genes were found, elevated levels of Monocarboxylate Transporter 1, a glial lactate transporter important during active myelination, were found in the PFC of exercising young adults. Overall our findings reveal that long-term exercise modulates PFC glial development and does so differentially in juvenile and young adult mice, providing insight into the cellular responses that may underlie cognitive benefits to teenagers and young adults in response to exercise. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 687-700, 2018.

This article presents the opto-mechanical design of a primary mirror assembly of a ground-based telescope with optimization algorithm. The prototype of ground-based telescope – GSO RC16 with 16 inches diameter blank primary mirror had been manufactured in 2016. However, a telescope with a blank primary mirror is too heavy to carry on for the stargazer. Besides, deformations caused by temperature difference and gravity will do significant effect to the large aperture mirrors with high optical performance requirements. In order to reduce the weight and maintain the stiffness simultaneously, the lightweight design and mounting interface design are critical and important. There are four types of system architectures in this project, including (1) two types of lightweight mirror designs - honeycomb type segments and sector type segments; (2) two types of mounting interface designs - retainer type support and CFRP type support. The optimization results showed that (1) the lightweight ratio of the primary mirrors are greater than 70%; and (2) the PV value of the mirrors supported by optimal mounting interfaces with gravity effect as a tilt of about 45 degrees and ±20°C temperature difference effectively less than 1/4 λ.

Objectives. To evaluate prospectively the prognostic power of urinary nuclear matrix protein-22 (NMP-22) for bladder cancer in Taiwanese screening and surveillance settings. Methods Single voided urine samples were obtained from 68 healthy individuals, 303 patients with benign urothelial diseases, and 28 patients with urogenital tumors. The NMP-22 levels in the urine samples were measured using enzyme-linked immunosorbent assay methods. Results The median NMP-22 level in healthy individuals and patients with benign and malignant disease was 5.9, 4.8, and 7.4 U/mL, respectively. The positive NMP-22 rate in healthy individuals and patients with benign and malignant disease was 4.4%, 17.2%, and 50%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value was 50%, 82.8%, 21.2%, and 94.7%, respectively, using 7.5 U/mL as the cutoff value. Conclusions Our data demonstrated that NMP-22 is not a good diagnostic tool for screening or follow-up surveillance of bladder cancer owing to its low sensitivity and positive predictive value. Nevertheless, it could be adopted as a tool to rule out the possibility or risk of developing bladder cancer because of its high negative predictive value in our study.

Summary Hedgehog is a regulatory protein during embryonic development and its abnormal activation in adult tissues has been implicated in tumorigenesis within sites where epithelial–mesenchymal interactions take place. In the prostate, Hedgehog signaling activation was observed during advanced cancer progression and metastasis, but whether Hedgehog overexpression can initiate prostate tumorigenesis remains unknown. We introduced a Hedgehog-expressing vector by intra-prostate injection and electroporation to address the effects of Hedgehog overexpression. The manipulation caused lesions with characteristic prostatic intraepithelial neoplasia or even prostatic cancer (CaP) phenotypes within 30 days, with Hedgehog overexpression demonstrated by immunohistochemistry and Western blot detections. The tumorigenic phenotypes were confirmed by discontinuity of basal cell marker p63, mix-up of CK-8/CK-18 positive epithelial cells in the stoma as well as absence of a-SMA positive fibro-muscular sheath. Comparable Hedgehog overexpression was found in human CaP specimen. Thus, Hedgehog overexpression induced prostate tumorigenesis starting from the normal status. Furthermore, a mouse prostate cancer model induced by Hedgehog overexpression was established and may be used for testing novel therapeutical approaches targeting at Hedgehog signaling pathway.