OBJETIVO: avaliar através da citopatologia, associada a técnica AgNOR, o reflexo da cessação do fumo sobre a velocidade de proliferação das células epiteliais descamadas de borda de língua (BL) e assoalho de boca (AB), ao longo do tempo. MÉTODOS: Foram incluídos na amostra inicial 138 indivíduos. As coletas foram realizadas em um momento inicial (T1), após 8-15 meses (T2) e após 16-30 meses (T3). Os participantes foram divididos em três grupos de acordo com os seguintes critérios: Grupo Controle (GC) (n=71): indivíduos atendidos na Faculdade de Odontologia da UFRGS, que nunca fumaram, e que ingeriam até 30g de álcool por semana. Grupo Abandono de Fumo (GAF) (n=26): indivíduos em acompanhamento no Grupo dos Fumantes do Hospital de Clínicas de Porto Alegra (HCPA), que fumavam no momento do inicial do trabalho, e que ao longo do tempo cessaram o hábito tabágico. Alcoolistas ou não. Grupo Fumo (GF) (n=41): indivíduos em acompanhamento no Grupo dos Fumantes do HCPA, que fumavam no momento do inicial do trabalho, e que não cessaram o hábito tabágico ao longo da pesquisa. Alcoolistas ou não. As amostras foram submetidas à técnica de AgNOR e quantificadas por três examinadores previamente calibrados. A média de AgNOR por núcleo (mAgNOR) e a porcentagem de células com mais de 1, 2 E 3 AgNORs (pAgNOR>1, pAgNOR>2 e pAgNOR>3) foram calculados nas 50 primeiras células, nucleadas, não sobrepostas, e bem distendidas. RESULTADOS: ao final dos tempos experimentais os grupos tinham 9 individuos em cada. Não foram observada diferença estatística do mAgNOR e pAgNOR>3 entre os grupos avaliados, nos diferentes tempos em ambos os sítios. Foi observada uma tendência à diminuição na velocidade de proliferação, no tempo intermediário, e uma tendência a aumentar no tempo final, em todos os grupos Em T1, os grupos expostos ao fumo (GAF e GF) apresentavam velocidade de proliferação mais elevada, se comparados ao GC no BL. No AB o GC apresenta valores maiores que GAF. Em T2, os indivíduos do GAF apresentaram uma redução da taxa de proliferação celular, em ambos os sítios analisados, maior do que GC e GF. Em T3 os valores retornam ao equilíbrio, exibindo valores maiores que os em T1. No BL o pAgNOR>1 e 2 mostrou uma diferença estatística entre os grupos em T1 e T2. O sítio AB apresentou diferença estatística no pAgNOR>1, em T2, mostrando que indivíduos do GC e GAF apresentam velocidade de proliferação menor quando comparados ao GF. CONCLUSÕES: O estudo mostrou que o GAF apresenta maior flutuação, de mAgNOR, que o GC e GF, ao longo do tempo. Estudo futuros ampliando o tempo de controle, controlando os agentes carcinógenos, e observando indivíduos com características populacionais seriam convenientes para buscar a padronização deste modelo de prevenção de câncer. / OBJECTIVE: evaluate, through cytopathology associated with AgNOR technique, the reflection of smoking cessation on the speed of proliferation of desquamated epithelial cells of tongue edge (TE) and mouth floor (MF) over time. METHODS: We included in the initial sample 138 individuals. Samples were collected at an early time (T1), after 8-15 months (T2) and after 16-30 months (T3). Participants were divided into three groups, according to the following criteria: control group (CG) (n = 71): patients seen at the Faculty of Dentistry at UFRGS, who had never smoked and who drank till 30g of alcohol a week. Abandonment group Smoke (AS) (n = 26): individuals in monitoring the Group of Smokers of Hospital de clínicas dePorto Alegre (HCPA), who smoked at the time of the initial work, and that over time ceased the smoking habit. Alcoholic or not. Tobacco group (TG) (n = 41): follow-up individuals in the group of smokers HCPA, who smoked at the time of the initial work, and that did not stop the smoking habit during the research. Alcoholic or not. Samples were subjected to AgNOR technique and quantified for three calibrated examiners. The average AgNOR per core (Magnor) and the percentage of cells with 1, 2 and 3 AgNOR (pAgNOR> 1, pAgNOR> 2 and pAgNOR> 3) were calculated on the first 50 cells, nucleated, nonoverlapping, and well- distended. RESULTS: At the end of the experimental time groups had 9 individuals in each. There were no statistical difference of mAgNOR and pAgNOR> 3 between the groups in different times on both sites. A tendency to decrease in the proliferation rate was observed, at the intermediate time, and a trend of increase in the end time for all groups in T1, the smoke exposed groups (AS and TG) showed higher proliferation rate, compared the CG in the TE. MF in the CG presents values greater than AS. In T2, AS individuals showed a reduction in cell proliferation rate in both sites evaluated greater than TG and CG. In T3 values return to equilibrium, exhibiting values greater than the T1. TE in the pAgNOR> 1 and 2 showed a statistical difference between groups in T1 and T2. The site MF showed statistical difference in pAgNOR> 1, T2, showing that CG and the AS show less proliferation of speed when compared to the TG. CONCLUSIONS: The study showed that the AS has greater fluctuation mAgNOR that CG and TG, over time. Future study extending the time control, controlling carcinogens, and observing individuals with population characteristics would be convenient to seek standardization of this cancer prevention model.

In 2007 Tennessee enacted and implemented the Nonsmoker Protection Act (NSPA) to protect nonsmokers by creating 100% smoke-free restaurants. Several venues were exempted, including age-restricted ones such as bars, and tobacco regulation was preempted. Thus, the NSPA is not equitable smoke free policy (SFP) because it has left vast segments of nonsmokers such as employees and patrons of bars unprotected from second-hand smoke (SHS) exposure and thwarted any local initiative to pursue 100% comprehensive SFPs. While this predisposes these nonsmokers to the health dangers of SHS exposure, it makes the NSPA incompatible with the objectives of the Healthy People 2020 and 2030 as well as goals of the state health plan. In 2021, the American Lung Association graded the NSPA “C,” and the United Health Foundation ranked it 42nd out of 50 states. This project assessed the effects of smoke-free venues across different economic domains through quantitative and qualitative data review to determine the implications for venues exempted by NSPA. By delineating any economic effects of SFP across several economic domains, the quantitative data gleaned from NAICS, Census Bureau, and Tennessee Dept. of Revenue were supplemented with interviews of establishments in Tennessee that voluntarily transitioned to smoke-free environment. A total of 7 such establishments with capacities ranging from 50 to over 69,000 people and number of employees ranging from 6 to over 1300 were interviewed. It was discovered that smoke-free environments have positive economic effects on restaurant establishments in Tennessee. By focusing on the SFP effect on restaurant establishments, the findings can be extrapolated to support the case for 100% smoke-free environments for other hospitality locations such as bars, music venues, and casinos. After analysis of trends for retail sales, number of establishments, employment, and payrolls by size of establishment and Metropolitan Statistical Area, a positive economic effect was identified for majority of these indicators between 2010 and 2019, a 10-year period following restaurants becoming smoke-free. Highlights include: Retail sales in Tennessee eating and drinking establishments increased by 62% The number of restaurant establishments increased by 16% Employment in the restaurant sector increased by 23% The qualitative data from the interviews reinforces these findings, with 100% of respondents supporting smoke-free age-restricted venues in their local communities. Thus, it can be inferred from these Tennessee-specific data with high degree of confidence that other hospitality venues will benefit economically in some way by becoming smoke-free with the following considerations: Provide protections from SHS exposure and health risks to nonsmokers; Do not adversely affect sales or employment in the hospitality, entertainment or sport industries, including bars, hotels and motels, and restaurants; Have strong public support and compliance.

A common industrial ventilation and pollution problem results when a thermally buoyant polluted plume of air must be exhausted away from a work area to allow achievement of air pollution standards. Generally, a close fitting canopy hood is one of the most effective means of exhaust containment; however, physical restrictions or the operation itself often prevent such an arrangement, and a hood located to the side of the operation is required. This arrangement requires the exhaust to bend and contain the vertically rising plume with a horizontal sweep of exhaust air across the surface of the operation. A review of available literature revealed a lack of the necessary theory and data needed to design a side draft hood based on plume dynamics. The purpose of this study, then, is to develop the theory relating the side draft hood size and required exhaust volume to the hot source characteristics and to test the theory in the laboratory.

Indiana University-Purdue University Indianapolis (IUPUI) / Cigarette smoking (CS) continues to be a significant modifiable factor contributing to a variety of diseases including cardiovascular, pulmonary and renal pathologies. It was suggested that smoking have detrimental effect of the body’s progenitor cells of bone marrow and peripheral organs. Since the concept of cell therapy that utilizes adipose stem/stromal cells (ASC) is gaining momentum it becomes critical to assess the therapeutic activities of the progenitors isolated from smokers. This study has revealed that CS negatively impacts the vasculogenic potential of ASC, in vitro, as well as weakening their therapeutic activity in vivo when tested in mouse model of hindlimb ischemia. We hypothesized that the decrease in vasculogenic activity of ASC is attributed to a higher level of expression of an angiostatic factor Activin A by ASC from CS donors. These findings clearly suggest that smokers should be evaluated for potential exclusion from early clinical trials of autologous cell therapies, or assessed as a separate cohort. The donor’s health status should be considered when choosing between autologous vs allogeneic cell therapies. We then examined the effect of CS on development of kidney pathology in mice. CS exposure led to decrease in kidney weights, capillary rarefaction, and cortical blood perfusion, and in parallel led to increase in kidney fibrosis and iron deposition. Interestingly, infusion of healthy ASC to the mice following CSexposure reversed CS-induced damages. This strongly support the notion that ASC-based therapy may provide rejuvenation effect. In the other subset of studies, we hypothesized that CS-induced lung emphysematous changes are preceded by suppression of bone marrow (BM) hematopoietic progenitor cells (HPC). We have revealed that intermittent BM mobilization with AMD3100 may mitigate the CS-induced myelo-suppression and deterioration of lung function and morphology. We observed that treatment of mice with AMD3100, while exposed to CS, preserves HPC at the levels of healthy control mice. Furthermore, AMD3100 treatment preserved lung parenchyma from pathological changes. These data suggest that while CS has a myelo-suppressive effect, administration of AMD3100 preserved BM-HPC and ameliorated lung damage.

No description available.

No description available.

Pulmonary tuberculosis (TB) remains one of the most infectious causes of death worldwide. Mycobacterium tuberculosis (M.tb), the causative agent of TB is transmitted via infectious aerosols, and in the majority of cases the bacteria is effectively controlled, by the host, resulting in a chronic latent infection. Currently, the only available vaccine is the Bacillus Calmette-Guérin (BCG), which despite being successful in preventing childhood disseminated forms of TB, has failed to control the adult pulmonary TB epidemic. One of the major contributing factors in the failure of the BCG is that although antigen-specific T cells are present at the time of M.tb infection, the recruitment of such T cells into the site of infection is significantly delayed. This delay, while reduced compared to non-vaccinated hosts, allows the bacteria to replicate unchecked within the lung and establish a “foothold” prior to the arrival of protective T cells and subsequent immune control. Thus, novel initiatives seek to close this “immunological gap” through increasing the level of protective T cell responses within the airway mucosa immediately following M.tb infection. We therefore investigated the impact of deliberate modulation of T cell geography following BCG vaccination on the outcome of pulmonary M.tb infection. In addition, a number of environmental factors are also thought to affect the site of M.tb infection: the respiratory mucosa. However, little is currently known about the effects of environmental exposure to allergens and other substances such as cigarette smoke on the outcome of pulmonary TB. Throughout this thesis we have investigated the mechanisms of immune protection and failure of protection against pulmonary M.tb infection within the respiratory mucosa. / Thesis / Doctor of Philosophy (Medical Science)

S100 calcium-binding protein A9 (S100A9) is elevated in plasma and bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), and aging enhances S100A9 expression in several tissues. Currently, the direct impact of S100A9- mediated signaling on lung function and within the aging lung is unknown. Here, we observed that elevated S100A9 levels in human BALF correlated with age. Elevated lung levels of S100A9 were higher in older mice compared with in young animals and coincided with pulmonary function changes. Both acute and chronic exposure to cigarette smoke enhanced S100A9 levels in age-matched mice. To examine the direct role of S100A9 on the development of COPD, S100a9 -/- mice or mice administered paquinimod were exposed to chronic cigarette smoke. S100A9 depletion and inhibition attenuated the loss of lung function, pressure-volume loops, airway inflammation, lung compliance, and forced expiratory volume in 0.05 s/forced vital capacity, compared with age-matched wild-type or vehicleadministered animals. Loss of S100a9 signaling reduced cigarette smoke-induced airspace enlargement, alveolar remodeling, lung destruction, ERK and c-RAF phosphorylation, matrix metalloproteinase- 3 (MMP-3), matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and keratinocyte- derived chemokine (KC) release into the airways. Paquinimod administered to nonsmoked, aged animals reduced age-associated loss of lung function. Since fibroblasts play a major role in the production and maintenance of extracellular matrix in emphysema, primary lung fibroblasts were treated with the ERK inhibitor LY3214996 or the c-RAF inhibitor GW5074, resulting in less S100A9-induced MMP-3, MMP-9, MCP-1, IL-6, and IL-8. Silencing Toll-like receptor 4 (TLR4), receptor for advanced glycation endproducts (RAGE), or extracellular matrix metalloproteinase inducer (EMMPRIN) prevented S100A9-induced phosphorylation of ERK and c-RAF. Our data suggest that S100A9 signaling contributes to the progression of smoke-induced and age-related COPD.

Indiana University-Purdue University Indianapolis (IUPUI) / The complex pathogenesis of emphysema involves disappearance of alveolar structures, in part attributed to alveolar cell apoptosis. The mechanism by which cigarette smoke (CS) induces alveolar cell apoptosis is not known. We hypothesized that ceramides are induced by CS via specific enzymatic pathways that can be manipulated to reduce lung cell apoptosis. CS increased ceramides in the whole lung and in cultured primary structural lung cells. Exposure to CS activated within minutes the acid sphingomyelinase, and within weeks the de novo- ceramide synthesis pathways. Pharmacological inhibition of acid sphingomyelinase significantly attenuated CS-induced apoptosis. To understand the mechanisms by which ceramides induce apoptosis, we investigated the cell types affected and the involvement of RTP801, a CS-induced pro-apoptotic and pro-inflammatory protein. Direct lung augmentation of ceramide caused apoptosis of both endothelial and epithelial type II cells. Ceramide upregulated RTP801 and the transgenic loss of RTP801 inhibited only epithelial, but not endothelial cell apoptosis induced by ceramide. In conclusion, CS induces acid sphingomyelinase-mediated ceramide upregulation and apoptosis in a cell-specific manner, which in epithelial cells involves induction of stress response proteins that may further amplify lung injury. Molecular targeting of amplification pathways may provide therapeutic opportunities to halt emphysema progression.

Flame and smoke image processing and analysis could improve performance to detect smoke or fire and identify many complicated fire hazards, eventually to help firefighters to fight fires safely. Deep Learning applied to image processing has been prevailing in recent years among image-related research fields. Fire safety researchers also brought it into their studies due to its leading performance in image-related tasks and statistical analysis. From the perspective of input data type, traditional fire research is based on simple mathematical regressions or empirical correlations relying on sensor data, such as temperature. However, data from advanced vision devices or sensors can be analyzed by applying deep learning beyond auxiliary methods in data processing and analysis. Deep Learning has a bigger capacity in non-linear problems, especially in high-dimensional spaces, such as flame and smoke image processing. We propose a video-based real-time smoke and flame analysis system with deep learning networks and fire safety knowledge. It takes videos of fire as input and produces analysis and prediction for flashover of fire. Our system consists of four modules. The Color2IR Conversion module is made by deep neural networks to convert RGB video frames into InfraRed (IR) frames, which could provide important thermal information of fire. Thermal information is critically important for fire hazard detection. For example, 600 °C marks the start of a flashover. As RGB cameras cannot capture thermal information, we propose an image conversion module from RGB to IR images. The core of this conversion is a new network that we innovatively proposed: Dual-Attention Generative Adversarial Network (DAGAN), and it is trained using a pair of RGB and IR images. Next, Video Semantic Segmentation Module helps extract flame and smoke areas from the scene in the RGB video frames. We innovated to use synthetic RGB video data generated and captured from 3D modeling software for data augmentation. After that, a Video Prediction Module takes the RGB video frames and IR frames as input and produces predictions of the subsequent frames of their scenes. Finally, a Fire Knowledge Analysis Module predicts if flashover is coming or not, based on fire knowledge criteria such as thermal information extracted from IR images, temperature increase rate, the flashover occurrence temperature, and increase rate of lowest temperature. For our contributions and innovations, we introduce a novel network, DAGAN, by applying foreground and background attention mechanisms in the image conversion module to help reduce the hardware device requirement for flashover prediction. Besides, we also make use of combination of thermal information from IR images and segmentation information from RGB images in our system for flame and smoke analysis. We also apply a hybrid design of deep neural networks and a knowledge-based system to achieve high accuracy. Moreover, data augmentation is also applied on the Video Semantic Segmentation Module by introducing synthetic video data for training. The test results of flashover prediction show that our system has leading places quantitative and qualitative in terms of various metrics compared with other existing approaches. It can give a flashover prediction as early as 51 seconds with 94.5% accuracy before it happens.