Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF.Methods: We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013. The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death.Results: The median age at autopsy was 71 years (range 47-86 years), and the subjects included 38 (73.1%) males. High-dose corticosteroid therapy was initiated in 45 (86.5%) patients after AE-IPF. The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases. Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma. In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy. In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections.Conclusions: The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions. Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment

Antioxidant activity of pomegranate juice reduces emphysematous changes and injury secondary to cigarette smoke in an animal model and human alveolar cells

Ahmad Husari,1,* Yasmine Hashem,1 Hala Bitar,1 Ghassan Dbaibo,2,3 Ghazi Zaatari,4 Marwan El Sabban5,* 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Pediatrics and Adolescent Medicine, Division of Pediatric Infectious Diseases, 3Department of Biochemistry and Molecular Genetics, 4Department of Pathology and Laboratory Medicine, 5Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon *These authors contributed equally to this work Background: Cigarette smoke (CS) increases oxidative stress (OS) in the lungs. Pomegranate juice (PJ) possesses potent antioxidant activities, attributed to its polyphenols. This study investigates the effects of PJ on the damaging effects of CS in an animal model and on cultured human alveolar cells (A549). Methods: Male C57BL/6J mice were divided into the following groups: Control, CS, CS + PJ, and PJ. Acute CS exposure was for 3 days, while chronic exposure was for 1 and 3 months (5 days of exposure/week). PJ groups received daily 80 µmol/kg via bottle, while other groups received distilled water. At the end of the experiments, different parameters were studied: 1) expression levels of inflammatory markers, 2) apoptosis, 3) OS, and 4) histopathological changes. In vitro, A549 cells were pretreated for 48 hours with either PJ (0.5 µM) or vehicle. Cells were then exposed to increasing concentrations of CS extracted from collected filters. Cell viability was assessed by counting of live and dead cells with trypan blue staining. Results: Acutely, a significant increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression, apoptosis, and OS was noted in CS when compared to Control. PJ significantly attenuated the expression of inflammatory mediators, apoptosis, and OS. Chronically (at 1 and 3 months), increased expression of TNF-α was observed, and lung sections demonstrated emphysematous changes when compared to Control. PJ supplementation to CS animals attenuated the increased expression of TNF-α and normalized lung cytoarchitecture. At the cellular level, CS extract reduced cellular proliferation and triggered cellular death. Pretreatment with PJ attenuated the damaging effects of CS extract on cultured human alveolar cells. Conclusion: The expression of inflammatory mediators associated with CS exposure and the emphysematous changes noted with chronic CS exposure were reduced with PJ supplementation. In vitro, PJ attenuated the damaging effects of CS extract on cultured human alveolar cells. Keywords: reactive oxygen species, antioxidants, acute lung injury, emphysema, pomegranate extract, cigarette smoke, inflammatory mediator

Electronic Cigarette Smoke Impairs Normal Mesenchymal Stem Cell Differentiation

Abstract Electronic cigarettes (e-cigarettes) are promoted as low-risk alternatives to combustible cigarettes. However, the effects of chronic inhalation of potential toxicants emitted by ecigarettes remain largely unexamined. It is conceivable that smoking-induced chronic diseases result in cellular injury, in the absence of effective repair by stem cells. This study evaluates the effect of cigarette and e-cigarette aerosol extracts on the survival and differentiation of bone marrow-derived mesenchymal stem cells (MSCs). MSC growth and osteogenic differentiation were examined after exposure to smoke extracts. Data revealed detrimental effects of both cigarette and e-cigarette extracts on MSC morphology and growth. Levels and activity of alkaline phosphatase, an osteogenic marker, decreased and induction of osteoblastic differentiation was impaired. Both smoke extracts prevented osteogenic differentiation from progressing, evident by decreased expression of terminal osteogenic markers and mineralization. Elevated levels of reactive oxygen species (ROS) were detected in cells exposed to smoke extracts. Moreover, decreased differentiation potential was concomitant with severe down-regulation of Connexin 43 expression, leading to the loss of gap junction-mediated communication, which together with elevated ROS levels, could explain decreased proliferation and loss of differentiation potential. Hence, e-cigarettes present similar risk as combustible cigarettes with respect to tissue repair impairment

Agile Approaches for Cybersecurity Systems, IoT and Intelligent Transportation

To adapt to the rapidly increasing vulnerabilities in software products and cyber threats that exploit them, security professionals are actively working with software developers to produce more secure systems. In software development, agile methods are increasingly adopted in critical software projects where security risks are prominent challenges. This adoption stems from the fact that agile methods are highly iterative and support delivering services and products in smaller batches which allows security professionals to seamlessly integrate software development security activities with agile methodologies. In addition, the iterative nature of agile software development encourages frequent inspections, tests, and patching of software systems to mitigate cybersecurity risks and vulnerabilities. Considering the massive growth of the Internet of Things (IoT) and Intelligent Transportation Systems (ITS) products, the challenge of software development while addressing the security and safety concerns of these devices will continue to increase. This paper presents a comprehensive and detailed review of agile software development in the context of IoT, ITS, and their cybersecurity and risk challenges. Furthermore, we provide a systematic comparison of the reviewed literature based on a set of defined criteria. Finally, we provide a broader outlook and an outline for designing future security-enhanced agile software development solutions for IoT and ITS systems

Comorbidities Predict Length of Stay Among Patients Admitted with Peripheral Artery Disease– An Analysis of The National Inpatient Sample.

The global prevalence of peripheral artery disease (PAD) is estimated to be about 120 million, making up about 25.6% of the worldwide burden of cardiovascular diseases (CVD). In the United States (U.S.), the prevalence of PAD is about 7%, representing nearly 8 million adults. There is a higher prevalence of disease in Blacks and non-Hispanic Whites, with approximately 30% of Blacks and 20% of non-Hispanic Whites developing PAD in their lifetime. The strong risk factors associated with PAD include smoking, diabetes, hypertension, age, and male sex. Our study aimed to estimate the effects of obesity, alcohol abuse, renal failure, and hypertension on patients’ length of stay (LOS) among patients admitted with a diagnosis of PAD. Using the 2012 U.S. National Inpatient Sample database, we included 336,790 patients with PAD as a separate comorbidity during their index admission. Our main outcome variable was patients’ total length of stay (LOS) during the index admission. We categorized LOS \u3c 1 into next day discharge (NDD) and LOS \u3e 1 into non-NDD. Our predictor variables were hypertension, obesity, alcohol abuse and renal failure. We ran descriptive statistics to delineate the baseline characteristics of our sample population, and bivariate analysis with t-test and chi-square analysis. Multivariable logistic regression was used to estimate odds of non-NDD given our comorbidities; obesity, hypertension, alcohol abuse, renal failure while adjusting for age, race, and sex. We reported frequencies, p-values, and odd ratios (ORs) at a 95% significance level with alpha at 0.05. Of our final sample, 54.8% were males while 45.2% were females and the mean age of patients was 71.7 + 12.8. Hypertension, obesity, alcohol abuse and renal failure were present in 75%, 12%, 3.4%, and 30.9% of patients, respectively. Majority (75%) of the patients were white, while Black and Hispanic patients made up 13.3% and 7.1%, respectively. In our adjusted model, we found that patients with hypertension had 12% lower odds of non-NDD (OR = 0.88, CI= 0.86-0.90, P\u3c0.0001) compared to those without hypertension, females had 20% increase in the odds of non-NDD compared to males (OR = 1.20, CI= 1.18-1.23, P\u3c0.0001), patients with obesity, alcohol abuse and renal failure had 39%, 43% and 45% increase in odds of non-NDD compared to those without these comorbidities. (OR = 1.39, CI= 1.34-1.44, P\u3c0.0001), (OR = 1.43, CI= 1.35-1.52, P\u3c0.0001), (OR = 1.45, CI= 1.42-1.49, P\u3c0.0001). Given the significant association between obesity, alcohol abuse, and renal failure with prolonged hospital stay in patients admitted to hospital with PAD, our study highlights the importance of adequate management of pre-existing patients\u27 comorbidities. This is expected to improve overall length of stay and total healthcare utilization and costs, among patients with PAD