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Jared T Hammill, Daniel C Scott, Jaeki Min, Michele C Connelly, Gloria Holbrook, Fangyi Zhu, Amy Matheny, Lei Yang, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit...
March 16, 2018: Journal of Medicinal Chemistry
Souheil El-Chemaly, Kevin J O'Brien, Steven D Nathan, Gerald L Weinhouse, Hilary J Goldberg, Jean M Connors, Ye Cui, Todd L Astor, Philip C Camp, Ivan O Rosas, Merte Lemma, Vladislav Speransky, Melissa A Merideth, William A Gahl, Bernadette R Gochuico
Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers...
2018: PloS One
Hussein Nassereddine, Nicolas Poté, Pasquale Tammaro, Anne Couvelard
Pulse (hyaline ring) granuloma, a rare entity first described in lung and oral cavity, has been reported under various names before the identification of hyaline rings as fragments of pulses (the edible seeds of legumes). Similar lesions were thereafter described in extra-oral localizations, mainly the gastrointestinal tract, or localizations having potential communication with the gastrointestinal tract. Recently, 2 reports described "spiral bodies" surrounded by foreign body-type multinucleated giant cell reaction in pulse granulomas, corresponding to remnant plant vascular structures (helical xylem elements)...
March 1, 2018: International Journal of Surgical Pathology
John Mark Cline, Greg Dugan, John Daniel Bourland, Donna L Perry, Joel D Stitzel, Ashley A Weaver, Chen Jiang, Artak Tovmasyan, Kouros Owzar, Ivan Spasojevic, Ines Batinic-Haberle, Zeljko Vujaskovic
Radiation injury to the lung is the result of acute and chronic free radical formation, and there are currently few effective means of mitigating such injury. Studies in rodents indicate that superoxide dismutase mimetics may be effective in this regard; however, studies in humans or large animals are lacking. We hypothesized that post-exposure treatment with the lipophilic mitochondrial superoxide dismutase mimetic, MnTnHex-2-PyP5+ (hexyl), would reduce radiation-induced pneumonitis and fibrosis in the lungs of nonhuman primates...
March 7, 2018: Antioxidants (Basel, Switzerland)
Sunghoon Choi, Haenghwa Lee, Donghoon Lee, Seungyeon Choi, Chang-Lae Lee, Woocheol Kwon, Jungwook Shin, Chang-Woo Seo, Hee-Joung Kim
PURPOSE: This work describes the hardware and software developments of a prototype chest digital tomosynthesis (CDT) R/F system. The purpose of this study is to validate the developed system for its possible clinical application on low-dose chest tomosynthesis imaging. METHODS: The prototype CDT R/F system was operated by carefully controlling the electromechanical subsystems through a synchronized interface. Once a command signal was delivered by the user, a tomosynthesis sweep started to acquire 81 projection views (PVs) in a limited angular range of ±20°...
March 3, 2018: Medical Physics
Sami Deniz, Hülya Şahin, Enver Yalnız
INTRODUCTION: Reduced exercise capacity is a main feature of Interstitial Lung Diseases (ILDs) and it is related to closely prognosis of these patients. Pulmonary Rehabilitation (PR) results to improve in peak exercise capacity, dyspnea and quality of life in ILDs. OBJECTIVES: We aimed to evaluate the benefits of PR in patients with ILDs and to determine whether there are similar gains in patients with severe ILD. METHODS: We recruited ILD stable patients...
March 2, 2018: Clinical Respiratory Journal
Mizuki Yagishita, Yuya Kondo, Toshihiko Terasaki, Mayu Terasaki, Masaru Shimizu, Fumika Honda, Ayako Oyama, Hiroyuki Takahashi, Masahiro Yokosawa, Hiromitsu Asashima, Shinya Hagiwara, Hiroto Tsuboi, Isao Matsumoto, Takayuki Sumida
Patients with clinically amyopathic dermatomyositis (CADM), a subset of dermatomyositis characterized by a lack of muscle involvement, frequently develop rapidly progressive and treatment-resistant interstitial lung disease. We report the case of a 49-year-old man who was diagnosed with CADM. He developed interstitial pneumonia, which did not respond to combination therapy with methylprednisolone pulse therapy, cyclophosphamide, and cyclosporine. We therefore attempted plasma exchange. After 7 courses of therapeutic plasma exchange, the interstitial pneumonia gradually improved...
February 28, 2018: Internal Medicine
Ke-Hao Huang, Ming-Cheng Tai, Lung-Chi Lee, Tzu-Heng Weng, Yi-Hao Chen, Li-Fan Lin, Jiann-Torng Chen, Da-Wen Lu, Ching-Long Chen
RATIONALE: Vogt-Koyanagi-Harada (VKH) syndrome is a rare disease and could be associated with autoimmune thyroid disease (AITD). This report was aimed to investigate the utility of F-fludeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) for the diagnosis of VKH syndrome with AITD and to perform a literature review on the association between the 2 diseases. PATIENT CONCERNS: A 55-year-old woman without the history of ocular trauma suffered from chronic headache...
March 2018: Medicine (Baltimore)
Jonathan R Weir-McCall, Patrick Sk Liu-Shiu-Cheong, Allan D Struthers, Brian J Lipworth, J Graeme Houston
BACKGROUND: Pulmonary pulse wave velocity (PWV) allows the non-invasive measurement of pulmonary arterial stiffening, but has not previously been assessed in COPD. The aim of the current study was to assess PWV in COPD and its association with right ventricular (RV) remodelling. METHODS: Fifty-eight participants with COPD underwent pulmonary function tests, 6-min walk test and cardiac MRI, while 21 healthy controls (HCs) underwent cardiac MRI. Thirty-two COPD patients underwent a follow-up MRI to assess for longitudinal changes in RV metrics...
February 27, 2018: European Radiology
Kyle M Jones, Carol A Stuehm, Charles C Hsu, Phillip H Kuo, Mark D Pagel, Edward A Randtke
Performing chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) in lung tissue is difficult because of motion artifacts. We, therefore, developed a CEST MRI acquisition and analysis method that performs retrospective respiration gating. Our method used an acquisition scheme with a short 200-millisecond saturation pulse that can accommodate the timing of the breathing cycle, and with saturation applied at frequencies in 0.03-ppm intervals. The Fourier transform of each image was used to calculate the difference in phase angle between adjacent pixels in the longitudinal direction of the respiratory motion...
December 2017: Tomography: a Journal for Imaging Research
Xiaoxing Cui, Feng Li, Jianbang Xiang, Lin Fang, Ming Kei Chung, Drew B Day, Jinhan Mo, Charles J Weschler, Jicheng Gong, Linchen He, Dong Zhu, Chengjian Lu, Hailong Han, Yinping Zhang, Junfeng Jim Zhang
BACKGROUND: More than 90% of the world's population lives in areas where outdoor air pollution levels exceed health-based limits. In these areas, individuals may use indoor air filtration, often on a sporadic basis, in their residences to reduce exposure to respirable particles (PM2.5 ). Whether this intervention can lead to improvements in health outcomes has not been evaluated. METHODS: Seventy non-smoking healthy adults, aged 19 to 26 years, received both true and sham indoor air filtration in a double-blinded randomized crossover study...
February 20, 2018: Environment International
Paul Robach, Joar Hansen, Aurélien Pichon, Anne-Kristine Meinild Lundby, Sune Dandanell, Gunnar Slettaløkken Falch, Daniel Hammarström, Dominik H Pesta, Christoph Siebenmann, Stefanie Keiser, Patricia Kérivel, Jon Elling Whist, Bent R Rønnestad, Carsten Lundby
Live high - train low (LHTL) using hypobaric hypoxia was previously found to improve sea-level endurance performance in well-trained individuals, however confirmatory controlled data in athletes are lacking. Here we test the hypothesis that natural-altitude LHTL improves aerobic performance in cross-country skiers, in conjunction with expansion of total hemoglobin mass (Hbmass , carbon-monoxide rebreathing technique) promoted by accelerated erythropoiesis. Following duplicate baseline measurements at sea level over the course of two weeks, nineteen Norwegian cross-country skiers (three women, sixteen men, age 20±2 yr, maximal oxygen uptake (VO2 max) 69±5 ml...
February 22, 2018: Scandinavian Journal of Medicine & Science in Sports
Ihsen Zairi, Lilia Baili, Khadija Mzoughi, Manel Dridi, Zouhaier Jnifene, Fatma Boussema
INTRODUCTION: Primary and secondary heart involvement in systemic sclerosis are important mortality predictors. Aim of this study was to investigate by standard echocardiography associated to pulsed-tissue Doppler imaging, six-minute walk test (6MWT) and BNP level cardiac manifestation in 30 patients with ScS and to establish a strategy to detect and to evaluate this complication. METHODS: This was a cross-sectional study conducted over a period of 16 months: a total of 30 consecutive patients with ScS diagnosed as proposed by the American college of Rheumatology and the European League Against Rheumatism 2013 and who were hospitalized in Internal Medicine department of Habib Thameur hospital underwent cardiac assessment...
March 2017: La Tunisie Médicale
Haiyan Chu, Junyi Xin, Qi Yuan, Xu Zhang, Wang Pan, Xinying Zeng, Yaoyao Chen, Gaoxiang Ma, Yuqiu Ge, Mulong Du, Na Tong, Xiaobo Li, Zhengdong Zhang, Meilin Wang
Numerous studies have shown that elderly people are susceptible to high-level particles with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) exposure. However, not all elderly people exposed to PM 2.5 suffer from diseases. In this study, we aim to establish a method to predict the vulnerable PM 2.5 -exposure individuals among elderly population. Fourteen elderly people were recruited from May 8 to July 4, 2016, in Nanjing, China. Ten physiological indicators were repeatedly measured for 15 times. Liner mixed-effects model, principal component analysis (PCA), and PM 2...
February 14, 2018: Environmental Science and Pollution Research International
Mehmet Dogan, Tolga Han Efe, Tolga Cimen, Cem Ozisler, Mehmet Ali Felekoglu, Ahmet Goktug Ertem, Mehmet Erat, Omer Yiginer, Murat Tulmac
OBJECTIVES: Systemic sclerosis (SSc) is a chronic, inflammatory, and autoimmune connective tissue disease that is associated with vascular lesions, and fibrosis of the skin and visceral organs. Cardiac complications may occur as a secondary effect of SSc as a result of pulmonary arterial hypertension and interstitial lung disease. The objective of this study was to assess whether the pulmonary pulse transit time (pPTT) could serve as a diagnostic marker for pulmonary arterial alterations in patients with SSc, prior to development of pulmonary hypertension...
February 14, 2018: Lung
Tokuhiro Matsubara, Tsutomu Nishida, Yu Higaki, Ryo Tomita, Hiromi Shimakoshi, Akiyoshi Shimoda, Naoto Osugi, Aya Sugimoto, Kei Takahashi, Dai Nakamatsu, Kaori Mukai, Masashi Yamamoto, Koji Fukui, Shiro Adachi, Masami Inada
A 42-year-old man was diagnosed with cStage IIIb malignant melanoma and underwent resection. After interferon-beta therapy, 18-fluorodeoxyglucose-positron emission tomography/computed tomography ( 18 F-FDG PET/CT) showed multiple lung metastases, and he received nivolumab (2 mg/kg) every 3 weeks, resulting in a total of 17 cycles. After treatment, 18 F-FDG PET/CT showed a significant decrease in the size of the metastases, but he had a Grade 4 ALT elevation. Liver histology revealed drug-induced liver damage...
February 9, 2018: Internal Medicine
Fei Lü, Wei Huang, David G Benditt
BACKGROUND: Current transcatheter ablation of ventricular tachycardia (VT) techniques is limited in part by its invasive nature and superficial depth of ablation lesions. OBJECTIVES: This study was aimed at evaluating the feasibility of targeted ablation of cardiac tissues using high-intensity focused ultrasound (HIFU) as a potential means for non-invasive ablation of VT. METHODS: Ablation of ventricular myocardium was performed in anesthetized closed-chest dogs using a HIFU therapeutic system that is currently used clinically for ablation of human solid tumors...
February 12, 2018: Journal of Cardiovascular Electrophysiology
Zhichao Zhang, Yuan Zhang, Houbing Song, Lina Yao, Anton Kos
Pulse diagnosis is an efficient method in traditional Chinese medicine for detecting the health status of a person in a non-invasive and convenient way. Jin's pulse diagnosis (JPD) is a very efficient recent development that is gradually recognized and well validated by the medical community in recent years. However, no acceptable results have been achieved for lung cancer recognition in the field of biomedical signal processing using JPD. More so, there is no standard JPD pulse feature defined with respect to pulse signals...
February 8, 2018: Journal of Biomedical Informatics
Richard W Chapman, Zhili Li, Michel R Corboz, Helena Gauani, Adam J Plaunt, Donna M Konicek, Franziska G Leifer, Charles E Laurent, Han Yin, Dany Salvail, Chad Dziak, Walter R Perkins, Vladimir Malinin
INS1009 is a long acting pulmonary vasodilator prodrug of treprostinil (TRE) that is formulated in a lipid nanoparticle for inhaled delivery by nebulization. This study examined the ability of INS1009 to inhibit vasoconstriction in the pulmonary vasculature of rats and dogs and the extent to which local activity within the lung contributes to its activity. Rats received a single dose of INS1009 by nose-only inhalation or were given a continuous intravenous (i.v.) infusion of TRE, followed by an i.v. challenge of the thromboxane mimetic pulmonary vasoconstrictor U46619 and the increase in pulmonary arterial pressure (PAP) was measured...
February 5, 2018: Pulmonary Pharmacology & Therapeutics
Ju-Lee Oei, Ola D Saugstad, Maximo Vento
PURPOSE OF REVIEW: To evaluate current evidence for the use of lower or higher oxygen strategies for preterm infant resuscitation RECENT FINDINGS: The equipoise for using higher fraction of inspired oxygen (FiO2) (>0.4) to initiate preterm infant respiratory stabilization has been lost. Recent meta-analyses of randomized controlled trials assessing outcomes after using higher (FiO2 ≥ 0.6) vs. lower (FiO2 ≤ 0.3) oxygen strategies to initiate preterm resuscitation shows no difference in the rates of death or major morbidities...
February 5, 2018: Current Opinion in Pediatrics
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