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1

Kharitonov, Sergei Alexandrovich. "Exhaled nitric oxide in airway diseases." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266411.

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2

Petersson, Christer. "Preschool children day-care, diseases and drugs : studies of risk factors for respiratory tract infections /." Lund : Dept. of Community Health Sciences, Lund University, 1994. http://books.google.com/books?id=Vs9sAAAAMAAJ.

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3

Almond, Elizabeth Jennifer Philippa. "Epstein-Barr virus infection of the lower respiratory tract." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1989. http://hub.hku.hk/bib/B31208484.

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4

Wrightson, John M. "Pathogen identification in lower respiratory tract infection." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:30c757ec-99b7-492e-a12e-ff996581863a.

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Treatment of lower respiratory tract infection (pneumonia and pleural infection) relies on the use of empirical broad spectrum antibiotics, primarily because reliable pathogen identification occurs infrequently. Another consequence of poor rates of pathogen identification is that our understanding of the microbiology of these infections is incomplete. This thesis addresses some of these issues by combining the acquisition of high quality lower respiratory tract samples, free from nasooropharyngeal contamination, with novel molecular microbiological techniques in an attempt to increase rates of pathogen identification. Four main areas are examined: (i) The role of so-called ‘atypical pneumonia’ bacteria in causing pleural infection. These pathogens have been previously identified in the pleural space infrequently and routine culture usually fails to isolate such bacteria. High sensitivity nested polymerase chain reaction (PCR) is a culture-independent technique which is used to undertake a systematic evaluation for these pathogens in pleural infection samples. (ii) The role of Pneumocystis jirovecii in pleural infection, either as a co-infecting pathogen or in monomicrobial infection. This fungus causes severe pneumonia, particularly in the immunosuppressed, but is increasingly recognised as a co-pathogen in community-acquired pneumonia, and is frequently isolated in the upper and lower respiratory tract in health. A high sensitivity real-time PCR assay is used to examine for this fungus. (iii) Ultra-deep sequencing of the 16S rRNA gene is used to perform a comprehensive microbial survey in samples taken from the multi-centre MIST2 study of pleural infection. The techniques employed allow analysis of polymicrobial samples and give very high taxonomic resolution, whilst incorporating methods to control for potential contamination. Further, these techniques provide confirmation of the results from the ‘atypical’ bacteria nested PCR study. (iv) Bedside ultrasound-guided percutaneous transthoracic needle aspiration (TNA) of consolidated lung is undertaken in patients with pneumonia, as part of the PIPAP study. An evaluation is undertaken of the efficacy and acceptability of TNA. Aspirate samples acquired are also processed using ultra-deep sequencing of the 16S rRNA gene. Other samples obtained as part of the PIPAP study, such as ‘control’ lung aspirates and ‘control’ pleural fluid samples, are similarly processed to enable calculation of sensitivity and specificity of the sequencing methodology.
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5

Wong, Chun-nin Adam, and 黃春年. "Analyses of influenza viral cytopathic effect in human lower respiratory tract." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290860.

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6

Enright, Mark Charles. "Molecular characterization of Moraxella catarrhalis." Thesis, University of Aberdeen, 1994. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158242.

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<I>Moraxella catarrhalis</I> is a gram-negative diplococcus which until recently was thought to be a harmless commensal. Increasing awareness has established the pathogenic nature of this organism and it is now recognised as a major cause of otitis media in children, exacerbations of chronic bronchitis in elderly patients and an occasional cause of invasive disease. <I>M. catarrhalis</I> is spread nosocomially especially in respiratory wards containing elderly patients. This study evaluated four methods for typing nosocomially spread isolates:- immunoblotting with normal human serum (NHS), and three DNA fingerprinting methods. The most discriminatory method found was restriction endonuclease analysis (REA) using <I>Taq</I> I, although immunoblotting with NHS and pulsed-field gel electrophoresis (PFGE) using <I>Sma</I> I sub-divided isolates grouped together by the other methods. PFGE using <I>Not</I> I only confirmed groupings made by other methods. A study of <I>M. catarrhalis</I> and phenotypically similar organisms was performed using comparisons of partial 16S rDNA sequence. 16S rDNA of <I>M. catarrhalis</I> strains from disparate geographical locations was found to be extremely conserved <I>M. catarrhalis</I> 16S rDNA was very similar to that of other <I>Moraxella</I> species whilst <I>Moraxella</I> species were found to be generally distinct from the <I>Neisseria</I> and <I>Kingella</I> species studied. These results confirm <I>M. catarrhalis</I> as a genuine member of the <I>Moraxellae</I>.
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7

Carstens, Ann. "Radiological tracheal dimensions of the normal Thoroughbred horse." Diss., University of Pretoria, 2008. http://hdl.handle.net/2263/30220.

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Respiratory conditions causing poor performance in horses are usually as result of upper respiratory tract diseases or are of pulmonary origin. The tracheal is rarely a cause of primary respiratory problems in the horse, but tracheal dimensions, particularly height, may be useful in evaluating upper repiratory tract conditions cranial to the trachea and lung pathology, due to resultant change in differential pressures between these areas. The normal radiological equine tracheal height along its length has as yet not been reported. Standing lateral radiographs of the cervical and thoracic trachea of 15 clinically normal sedated Thoroughbred horses, 3-6 years old, were made at peak inspiration and end expiration. Maximum height of the larynx, and trachea at the level of the third and fifth cervical vertebra, at the level of the first thoracic vertebra, carina and the left and right primary bronchi were measured. Ratios of laryngeal height relative to the third cervical vertebral body length and tracheal heights relative to the vertebral body lengths of adjacent third and fifth cervical vertebrae and first thoracic vertebra, and carina heights relative to a mid-thoracic vertebra, respectively were made, as well as tracheal height at the fist thoracic vertebra ratio with the thoracic inlet height. Known size metallic markers were used to determine magnification corrected tracheal heights in the sagittal plane and effect of body mass and height at the withers on tracheal height was determined. The magnification corrected radiological airway heights at end expiration and peak inspiration were measured and respectively the mean values were found to be: laryngeal height: 5.89 cm and 5.86 cm, tracheal height at the third cervical vertebra: 4.17 cm and 4.04 cm, tracheal height at the fifth cervical vertebra: 3.62 cm and 3.59 cm, tracheal height at the first thoracic vertebra: 3.4 cm and 3.23 cm and carina height: 3.85 cm and 4.12 cm. The ratios of these measurements to nearby vertebral body lengths were respectively: laryngeal height at the third cervical vertebra: 0.56 and 0.56, tracheal height at the third cervical vertebra: 0.4 and 0.39, tracheal height at the fifth cervical vertebra: 0.37 and 0.37, tracheal height at the first thoracic vertebra: 0.59 and 0.59, and carina height: 0.91 and 0.94. The ratio tracheal height at the first thoracic vertebra to the thoracic inlet respectively 0.15 and 0.15. Although there was no statistical difference in the data, there was a trend towards a higher tracheal height at expiration. No correlation was found between tracheal height and body mass or tracheal height and height at the withers, and measured tracheal height was generally lower than predicted tracheal height, possibly as result of sedation used. The small range of body mass and height in this study as well as the relatively small number of horses evaluated may account for the lack of correlation to predicted tracheal height. This study in normal horses may serve as a reference when radiologically evaluating cases of upper respiratory tract and lung pathology, where the tracheal dimensions may differ significantly due to differences in airway resistance and biomechanics. Radiographs to evaluate tracheal height can be made independent of respiratory phase in sedated horses, and it is recommended that ratios of tracheal height to an adjacent vertebral body length are more reliable values to compare within and between horses. It is recommended to take tracheal height measured at the fifth cervical vertebra since this measurement showed a slightly smaller standard deviation than at other sites measured as well as a medium amount of clinical effect. If only thoracic radiographs are made, measurements of tracheal height at the thoracic inlet is the alternative (the standard cranioventral view), but it is recommended to include the distal aspect of the first rib if the thoracic inlet is to be measured.<br>Dissertation (MMedVet)--University of Pretoria, 2008.<br>Companion Animal Clinical Studies<br>unrestricted
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8

Bello, Ortí Bernardo. "Haemophilus parasuis host-pathogen interactions in the respiratory tract." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/312855.

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En el sector veterinario, la enfermedad de Glässer es un proceso patogénico frecuente que conduce a pérdidas económicas considerables. Esta enfermedad es causada por Haemophilus parasuis. Aunque se ha llevado a cabo un esfuerzo importante hacia la comprensión de los factores que intervienen en la evolución de la enfermedad, la falta de completa protección de las vacunas comerciales sugieren que debe dirigirse más trabajo hacia el estudio de este proceso patogénico. Para aumentar el conocimiento en patogénesis desarrollamos una serie de experimentos. Es bien sabido que existen diferentes cepas de H. parasuis, desde no virulentas a altamente virulentas. Ciertos mecanismos patogénicos se atribuyen a la virulencia de algunas cepas, mientras que las cepas no virulentas solamente colonizan el tracto respiratorio superior y no son capaces de causar enfermedad. Estos diferentes grados de virulencia podrían ser apreciados durante los primeros pasos de la infección. De este modo, usando muestras de las vías respiratorias de lechones infectados con dos cepas virulentas (Nagasaki y IT29755) y dos cepas no virulentas (SW114 y F9), se desarrollaron métodos de inmunohistoquímica e inmunofluorescencia, así como una doble tinción de H. parasuis y macrófagos/neutrófilos. Nuestros resultados revelaron que las cepas virulentas de H. parasuis estaban presentes en cornete nasal, tráquea y pulmón. Detalles adicionales mostraron que las cepas virulentas de H. parasuis no solo se asociaron a macrófagos y neutrófilos del pulmón, sino también a células tipo neumocitos. Por lo tanto, las cepas virulentas de H. parasuis fueron capaces de adherirse al epitelio de las vías respiratorias, invadir y diseminarse en el huésped. Por el contrario, las cepas no virulentas apenas se detectan en el tracto respiratorio. La cepa virulenta Nagasaki mostró patrones de biofilm en tráquea, que nos hizo cuestionar el papel de la formación de biofilm en la infección. Dado que la literatura publicada anteriormente indicaba que la formación de biofilm se presentaba principalmente en cepas no virulentas, se realizó una investigación adicional en esta dirección para comparar la formación de biofilm en cepas virulentas y no virulentas de H. parasuis. Nuestros resultados confirmaron que la capacidad de formar biofilm in vitro se presenta principalmente en cepas no virulentas. Por tanto, se secuenció el transcriptoma de la cepa no virulenta F9 durante su crecimiento en biofilm utilizando un modelo in vitro. Los resultados sugieren que bajo condiciones de biofilm, H. parasuis muestra un metabolismo reducido, demostrado por el perfil de expresión génica. Además, algunos de los genes inducidos en condiciones de biofilm eran específicos de las cepas no virulentas, como la hemaglutinina filamentosa fhaB, previamente asociada a la formación de biofilm en otras bacterias. Finalmente, la observación de cepas virulentas de H. parasuis en pulmón durante la infección motivó la secuenciación del transcriptoma de una cepa patógena en esta ubicación. Se determinó la expresión génica después de una infección corta in vivo y tras la inoculación de pulmón ex vivo. Los resultados mostraron tendencias comunes en la expresión génica de H. parasuis bajo infección pulmonar in vivo y ex vivo, como la reducción del metabolismo y la expresión de genes implicados en la adquisición de nutrientes, lo que podría indicar una estrategia de supervivencia en estas condiciones. Durante la infección pulmonar también se detectaron genes únicos de cepas virulentas de H. parasuis que codifican para proteínas de membrana externa. Estos genes requerirán una mayor caracterización como factores de virulencia, pudiendo ser también útiles para desarrollar nuevos antibióticos y vacunas. Nuestros resultados también apoyan el uso de explantes de pulmón como modelo para estudios de patogenicidad de otras bacterias respiratorias.<br>In the veterinary field, Glässer’s disease is a common pathogenic process that leads to considerable economic losses. This disease is caused by Haemophilus parasuis. Although considerable effort has been focused towards understanding the factors involved in disease outcome, evidences of lack of complete protection of commercial vaccine formulations suggest that more work should be addressed towards understanding this pathogenic process. To fill this gap in pathogenesis knowledge we developed a series of experiments. It is well known that different H. parasuis strains exist, ranging from non-virulent to highly virulent. Particular pathogenic mechanisms are attributed to virulence strains, while non-virulent strains only colonize the upper respiratory tract and are unable to cause disease. It is expected that these different virulence degrees can be appreciated also during the early steps of infection. Using samples from the respiratory tract of piglets infected with two virulent strains (Nagasaki and IT29755) and two non-virulent strains (SW114 and F9), immunohistochemistry and immunofluorescence methods were developed, as well as a double staining targeting H. parasuis and macrophage/neutrophil cells. Our results revealed that H. parasuis virulent strains were present in nasal, trachea and lung locations. Additional details showed that virulent H. parasuis was associated to macrophages and neutrophils in lung, but also to pneumocyte-like cells. Thus, virulent H. parasuis was able to attach to respiratory tract epithelia, invade and disseminate into the host. On the contrary, non-virulent strains were barely detected in the respiratory tract. Biofilm-like patterns were displayed by virulent Nagasaki strain in trachea and this made us question the role of biofilm formation in infection. Since previously published reports indicated that biofilm formation was mainly present in non-virulent strains, we performed additional research in this direction to compare biofilm formation with virulent and non-virulent H. parasuis strains. Our results confirmed that the capacity to form biofilm in vitro was mainly presented by non-virulent strains. Thus, we sequenced the transcriptome of non-virulent F9 strain under biofilm growth using an in vitro model. Results suggested that under biofilm conditions H. parasuis showed a low metabolic state, as indicated by the gene expression profile. Some of the genes induced under biofilm conditions were specific of non-virulent strains, as the filamentous hemagglutinin fhaB, which has been associated to biofilm formation in other bacteria. Additionally, the observation of virulent H. parasuis strains in the lung during infection inspired us to sequence the transcriptome of a pathogenic strain in this location. Gene expression was determined after a short in vivo infection and after ex vivo lung inoculation. Results showed common trends in H. parasuis gene expression under in vivo and ex vivo lung infection, such as reduced metabolism and higher expression of genes involved in nutrient acquisition, which could indicate a survival strategy under these conditions. Genes unique of virulent H. parasuis strains coding for outer membrane proteins were also detected during lung infection. These genes would require further characterization as virulent factors and could be also useful to develop new antimicrobials and vaccines. Our results also support the use of lung explants as models for pathogenicity studies of respiratory bacteria.
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9

Nathell, Lennart. "Some determinants of sick leave for respiratory disease : occupation, asthma, obesity, smoking, and rehabilitation /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-301-5/.

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10

Paudyal, Priyamvada. "Respiratory symptoms and lung function in relation to cotton dust and endotoxin exposure in textile workers in Nepal." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=166944.

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Background: Cotton workers are highly exposed to organic dust. Inhalation of cotton based particulate has been associated with various respiratory symptoms and impaired lung function. This study investigates the respiratory health profile of textile mill workers in Nepal in relation to dust and endotoxin exposure. Methods: This study was conducted in four sectors (garment, carpet, weaving and recycling) of the textile industry in Kathmandu, Nepal. A total of 938 individuals completed a health questionnaire and performed spirometry. A subset of 384 workers performed cross-shift spirometry. Personal exposure to inhalable dust and airborne endotoxin was measured during a full-shift for a 114 workers. Results: Geometric mean concentrations of personal exposure to cotton dust and endotoxin were 0.81 mg/m3 and 2160 EU/m3 respectively. Overall prevalence of persistent cough, persistent phlegm, wheeze, breathlessness and chest tightness were 8.5%, 12.5%, 3.2%, 6.5%and 3.6% respectively. Symptoms were most common among the recyclers and less in the garment sector. Exposure to inhalable dust significantly predicted the symptoms of persistent cough and chest tightness. Significant cross-shift reduction in FEV1, FVC, and FEF25_75 were measured in the textile workers (p<0.001 for all); reductions being greater in the recyclers (-143 ml) and smallest in the garment workers (-38 ml) (p=0.012). Cross-shift reduction in FEV1 was significantly predicated by exposure to inhalable dust. Exposure to endotoxin did not correlate with any of the respiratory symptoms nor to lung function. Conclusion: The measured association between exposure to inhalable dust and reporting of respiratory symptoms and lung function suggests that despite high levels of endotoxin exposures, inhalable dust is the driver for these effects and attention should turn to what might be the toxic component in this dust other than endotoxin.
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11

Veeranki, Sreenivas P., Shimin Zheng, Yan Cao, and Arsham Alamian. "Association of Serum Vitamin D Levels with Respiratory and Atopic Diseases." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/91.

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Background: Vitamin D is known to be associated with inflammatory diseases, but its relationship with allergic diseases is unclear. The study objective is to determine the association of serum vitamin D levels and markers of wheeze, asthma and atopy. Methods: Data (n = 9,463) on serum vitamin D levels and atopy were obtained from 2005-2006 National Health and Nutrition Examination Survey. Serum vitamin D level was categorized into four groups: Normal (≥30ng/ml), Insufficient (21-29ng/ml), Deficient (11-20ng/ml) and Severely Deficient (≤10ng/ml). Atopy was defined as at least 1 positive allergen-specific IgE level measured for a panel of 5 common aeroallergens- cat, dog, house dust mite, cock roach and Alternaria species. Doctor-diagnosed asthma and wheeze in the previous 12 months were assessed by means of questionnaire. Multivariable logistic regression analyses were conducted to investigate the association of serum vitamin D with wheeze, asthma and atopy adjusting for age, sex, race, smoking, outdoor physical activity, body mass index and poverty income ratio. Results: Overall, 15%, 14% and 28% of subjects had wheeze, asthma and atopy, respectively. Approximately 21% had normal serum vitamin D levels, while 35%, 28% and 5% had insufficient, deficient and severely deficient levels. Compared to subjects with normal vitamin D levels, those with insufficient, deficient and severely deficient levels had increased relative odds of wheeze and atopy with highest adjusted estimates in subjects with severe vitamin D deficiency (adjusted odds ratio [OR] 2.31, 95% Confidence Interval [CI] 1.73-3.10 for wheeze; OR 1.49, 95% CI 1.17-1.89 for atopy). Conclusion: Low serum vitamin D levels were found to be associated with wheeze and atopy. Findings contribute to ongoing efforts to understanding the role of vitamin D in atopic diseases.
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12

Yip, Chik-yan. "Epidemiology of novel viruses associated with human respiratory tract infections in Hong Kong." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41508713.

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13

Soh, Kim Lam. "Knowledge about nosocomial pneumonia prevention among critical care nurses in New Zealand a thesis presented in partial fulfillment of the requirement for the degree of Master of Health Science, Auckland University of Technology, September 2003 /." Full thesis. Abstract, 2003. http://puka2.aut.ac.nz/ait/theses/SohK.pdf.

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Thesis (MHSc--Health Science) -- Auckland University of Technology, 2003.<br>Appendix B not included in e-thesis. Also held in print (128 leaves, 30 cm.) in Akoranga Theses Collection. (T 610.7361 SOH)
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Yip, Chik-yan, and 葉植恩. "Epidemiology of novel viruses associated with human respiratory tract infections in Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41508713.

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15

Gunnbjörnsdóttir, María Ingibjörg. "Asthma and respiratory symptoms in Nordic countries, environmental and personal risk factors /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7076.

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16

Palmer, Benjamin L. "Effect of welder group size on individual respiratory exposures to welding fumes." Oklahoma City : [s.n.], 2010.

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17

Veeranki, Sreenivas P., Yan Cao, Shimin Zheng, Megan Quinn, and Liang Wang. "Two Faces in the Lung! Vitamin E and Respiratory and Atopic Diseases." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/88.

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18

Vian, Bruna Scharlack 1979. "Efeito da aplicação nasal de diferentes soluçõeo salinas sobre os sintomas, sensibilidade olfativa e expressão de fator crescimento neural (NGF) em pacientes com rinopatia alégica persistente." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311764.

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Orientador: Ricardo de Lima Zollner<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas<br>Made available in DSpace on 2018-08-19T21:14:23Z (GMT). No. of bitstreams: 1 Vian_BrunaScharlack_M.pdf: 1879886 bytes, checksum: d9b52c103c4a6cca51810138e9c47e14 (MD5) Previous issue date: 2012<br>Resumo: A rinite alérgica (RA) é definida como uma inflamação da mucosa nasal, resultando em sintomas nasais que incluem rinorréia, obstrução, prurido e espirros. O fator de crescimento neural (NGF) está envolvido na fisiopatologia de inflamação alérgica. Soluções salinas nasais em diversas concentrações têm sido usadas para prevenir ou reduzir sintomas alérgicos, porém as concentrações ideais das soluções de cloreto de sódio nasal ainda não estão bem estabelecidas na literatura disponível. O objetivo desse estudo foi avaliar o efeito das soluções salinas: isotônica (ISO), hipertônica 3% (HIPER) e agua destilada (HIPO) em pacientes com RA persistente, comparando os escores clínicos dos sintomas nasais, avaliação do escore olfativo e a expressão gênica de NGF como marcador inflamatório do conteúdo celular nasal e considerando temperatura e umidade nos diferentes períodos em que utizaram as soluções. Trinta (30) pacientes com diagnóstico de RA persistente iniciaram o estudo, porem apenas 13 terminaram. Os pacientes foram divididos em 3 grupos aleatorizados que utilizaram as 3 soluções: ISO, HIPER e HIPO em 3 períodos diferentes (P1, P2 e P3). Os critérios clínicos de avaliação dos sintomas eram avaliados por meio de "Questionário Validado", onde somava-se o total do escore dos sintomas nasais (TESN). Para a avaliação do sintoma olfato era aplicado um escore olfativo de 0 a 8 com diluições de essência de eucalipto. Foi realizada coleta de material da mucosa nasal para o estudo da expressão gênica de NGF por meio de Reação de Polimerase em Cadeia (PCR). Os resultados observados neste estudo foram que no P1, os pacientes apresentaram melhora do TESN (p=0.004), quando comparada com a HIPER. Tanto o grupo que iniciou o tratamento com a solução ISO (p= 0,056), quanto o grupo que iniciou com HIPO (p= 0,063) tiveram uma tendência de melhora quando comparada com a HIPER. Todos os grupos no P1 apresentaram melhora do escore olfativo. O grupo que iniciou com a solução HIPER mostrou valores de expressão de NGF significativamente maiores (p=0,023). Conclui-se então, que as soluções salinas podem ser utilizadas como tratamento adjuvante na RA, pois melhorou os sintomas e melhorou o escore olfativo, porém a solução HIPER aumentou expressão de NGF na mucosa nasal<br>Abstract: Allergic rhinitis (AR) is defined as inflammation of the nasal mucosa, resulting in nasal symptoms including rhinorrhea, obstruction, itching and sneezing. Neural growth factor (NGF) is involved in the pathophysiology of allergic inflammation. Nasal saline solutions, at various concentrations, have been used to prevent or reduce allergic symptoms, but the ideal concentration of nasal sodium chloride solutions are not well established in the literature. The objective were to evaluate the effect of salt solutions such as isotonic (ISO), hypertonic (3% NaCl - HYPER) and hypotonic (sterile distilled water - HYPO) in patients with persistent allergic rhinitis, comparing clinical scores of nasal symptoms and olfactory score, as well as NGF expression as an inflammatory marker of nasal cell content. Thirteen (13) patients of thirty (30) with diagnosed persistent AR were divided into three randomized groups that used three solutions: ISO, HYPO and HYPER, during three periods (P1, P2 and P3). Clinical evaluation criteria of symptoms were determined by a validated questionnaire that evaluated the total nasal symptom score (TNSS). Nasal mucosa material was collected to analyze NGF expression assessed by the Polymerase Chain Reaction (PCR). The results were: patients showed an improvement in TNSS (p = 0.004) during the first period. The group that began treatment using the ISO solution (p = 0.056), as well the group that started using the HYPO (p = 0.063) showed a trend of improvement in TNSS, when compared with the HYPER group. All groups showed improvement in olfactory score during de first period. With regard to NGF gene expression, the group treated with the HYPER solution showed significantly higher levels (p=0.023) of expression compared with patients treated with the other nasal solutions. The conclusion was that the salt solutions may be used as adjuvant therapy in AR, due to the fact that they improve symptoms and olfactory score. Hyper saline solution can increase the expression of NGF in nasal mucosa<br>Mestrado<br>Clinica Medica<br>Mestre em Clinica Medica
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Piedade, Cátia Marina Rodrigues da. "Etiologia das infeções respiratórias virais em crianças em idade pré-escolar." Master's thesis, Faculdade de Ciências Médicas. UNL, 2013. http://hdl.handle.net/10362/9999.

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RESUMO: Os vírus respiratórios continuam a ocupar um papel relevante na morbilidade e mortalidade infantil, tendo na última década sido alargado o espectro de vírus potencialmente causadores das infeções respiratórias. O diagnóstico destas infeções pode ser efetuado por várias metodologias, sendo as técnicas de biologia molecular consideradas as mais sensíveis para este fim. No âmbito do Projeto Ambiente e Saúde em Creches e Infantários (ENVIRH) foi efetuada uma comparação da prevalência dos principais vírus respiratórios em crianças em idade pré-escolar, com critérios de infeção respiratória, recorrendo a técnicas de biologia molecular, em duas populações: crianças que se encontravam na escola/domicilio e crianças que recorreram a uma urgência hospitalar. O estudo decorreu em dois períodos, de Fevereiro a Maio de 2011 e de Outubro de 2011 a Abril de 2012. Foram efetuadas duas colheitas de zaragatoas, uma nasal e outra orofaríngea. A metodologia utilizada para a identificação viral nas amostras foi a PCR e RT-PCR multiplex em tempo real. Os vírus pesquisados foram: Influenza A e B, Parainfluenza 1-4, Metapneumovirus humano, Vírus Sincicial respiratório (VSR), Rinovírus, Enterovírus, Coronavírus e Bocavirus. Foram realizadas 100 colheitas em crianças com idades compreendidas entre os 5 meses e os 5 anos. Foram obtidas 64 amostras dos infantários/domicílios, das quais 47 foram positivas. Da urgência Hospitalar obtiveram-se 36 amostras, em que 32 foram positivas. O vírus da gripe A (H3) foi o mais frequentemente detetado nas duas populações, mas apenas durante o surto de 2012. O VSR e os adenovírus foram mais frequentes nas crianças que recorreram ao hospital, ao contrário dos enterovirus e dos coronavírus, que não foram detetados nesta população. Os bocavirus nunca foram detetados isoladamente. Este estudo reforça a importância de se utilizarem técnicas de biologia molecular para o diagnóstico etiológico das infeções respiratórias, devido à elevada sensibilidade das mesmas, o que se reflete na elevada percentagem de amostras positivas. O facto de se utilizarem técnicas “multiplex”, que permitem a pesquisa simultânea de vários vírus, facilita a deteção de um maior espectro destes agentes. A elevada prevalência de Influenza A H3N2 deveu-se ao facto de grande parte do estudo ter coincidido com um período de surto por este vírus. O sistema de alerta montado durante o projeto ENVIRH pareceu promissor para uma eventual utilização futura em períodos de atividade gripal.--------------ABSTRACT: In the last decade, as respiratory viruses keep representing a relevant factor in child morbidity and mortality, the spectrum of viruses that may potentially cause respiratory infections has been widened. Within the several methodologies that may be applied in the diagnosis of these types of infections, the ones that use molecular biology are considered to be the most sensitive. The Environment and Health in Daycares and Nurseries Project (ENVIRH) arranged for a study, by means of molecular biology techniques, on the main respiratory viruses' influence in pre-school aged children with respiratory infection symptoms. This study compared children in two different populations: children at school or at home and children that were taken to a hospital emergency service. The study was conducted in two different time periods, one from February to May 2011 and the other from October 2011 to April 2012. During this time, two swab collections were held, one nasal and one oropharyngeal. PCR and RT-PCR multiplex in real time techniques were used for viral identification of the samples, searching for the viruses Influenza A and B, Parainfluenza 1-4, human Metapneumovirus, Respiratory Sincytial Virus (RSV), Rhinovirus, Enterovirus, Coronavirus and Bocavirus. One hundred (100) collections were held in children between the ages of 5 months and 5 years, sixty-four (64) at home/school and thirty-six (36) at the hospital's emergency service. From a total of seventy-nine (79) positive samples, forty-seven (47) were obtained at home/school and thirty-two (32) at the hospital. The virus detected the most in both populations was the Influenza A (H3), but only during the outbreak of 2012. Unlike the enteroviruses and coronaviruses, that were not detected within this population, the RSV and the adenoviruses were most common within the children at the hospital. Bocaviruses were never detected isolated from other viruses. The high percentage of positive samples reinforces the significance of using molecular biology techniques for the etiological diagnosis of respiratory infections. The use of multiplex techniques, that make the simultaneous search for multiple viruses possible, enhances the detection of a larger spectrum of such agents. Most of the study coincided with an outbreak of the Influenza A H3N2 virus, thus explaining the high number of its cases identified. The alert system set up during the ENVIRH project looked promising enough for eventual periods of flu activity in the future.
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20

Yano, Yuichi. "Bayesian and geostatistical analysis of the effect of air pollution on asthma hospitalisation in Perth." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2010. https://ro.ecu.edu.au/theses/1837.

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Asthma is a respiratory disease which carries a risk of hospitalisation in severe cases. Numerous studies have shown that air pollution is one of the factors that exacerbates asthma symptoms and while population increases in asthma hospitalisation have been shown for Perth, the nature of exposure and risk across areas within the metropolitan area have not been determined. This study investigates the effect of air pollution concentrations on asthma hospitalisation through building a mathematical model which calculates the risk of asthma hospitalisation for Perth metropolitan areas. The data used in this study are: averaged emission inventory data (NO, CO and PM10) in 2006 and records of asthma hospitalisation for 75 postcodes in the Perth metropolitan region. A time series analysis of the data shows that the seasonality for NO2 and CO coincides with the health data seasonality for all years and all postcode groups. The study makes use of geostatistical and statistical techniques within the hierarchical stages of modelling procedure. The air pollutant concentration in Perth was estimated with the Gaussian Plume Model (GPM) and the lognormal kriging. The risk of asthma hospitalisation was calculated using Bayesian Hierarchical Model (BHM). The outputs from the air pollution model and asthma risk model were incorporated in a Generalised Linear Model (GLM), where the risk of asthma hospitalisation was regressed against the air pollution concentration estimate. The results of GLM analysis showed that the influence of air pollutant on asthma hospitalisation risk varied over time and space. The comparisons of the yearly GLM output suggested that the asthma hospitalisation risk has decreased over the study period, although few acute rises in the risk were observed in some years. This study has demonstrated how environmental data and health data could be integrated in a series of mathematical modelling procedures for predicting possible health hazards at a postcode level.
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21

Barnes, Steve R., Zimy Wansaula, Kristen Herrick, et al. "Mortality estimates among adult patients with severe acute respiratory infections from two sentinel hospitals in southern Arizona, United States, 2010–2014." BIOMED CENTRAL LTD, 2018. http://hdl.handle.net/10150/627114.

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Background: From October 2010 through February 2016, Arizona conducted surveillance for severe acute respiratory infections (SARI) among adults hospitalized in the Arizona-Mexico border region. There are few accurate mortality estimates in SARI patients, particularly in adults >= 65 years old. The purpose of this study was to generate mortality estimates among SARI patients that include deaths occurring shortly after hospital discharge and identify risk factors for mortality. Methods: Patients admitted to two sentinel hospitals between 2010 and 2014 who met the SARI case definition were enrolled. Demographic data were used to link SARI patients to Arizona death certificates. Mortality within 30 days after the date of admission was calculated and risk factors were identified using logistic regression models. Results: Among 258 SARI patients, 47% were females, 51% were white, non-Hispanic and 39% were Hispanic. The median age was 63 years (range, 19 to 97 years) and 80% had one or more pre-existing health condition; 9% died in hospital. Mortality increased to 12% (30/258, 30% increase) when electronic vital records and a 30-day post-hospitalization time frame were used. Being age >= 65 years (OR = 4.0; 95% CI: 1.6-9.9) and having an intensive care unit admission (OR = 7.4; 95% CI: 3.0-17.9) were independently associated with mortality. Conclusion: The use of electronic vital records increased SARI-associated mortality estimates by 30%. These findings may help guide prevention and treatment measures, particularly in high-risk persons in this highly fluid border population.
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22

Jenkins, Bradlee A., and L. Lee Glenn. "Cystic Fibrosis Carrier Screening Attitudes and Multiple Hypothesis Testing." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/7466.

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The recent study by Cunningham, Lewis, Curnow, Glazner, and Massie [1] on the attitudes of respiratory physicians and clinic coordinators towards cystic fibrosis (CF) carrier screening drew several unsupported conclusions because the α level of 0.05 was not corrected for the large number of hypothesis tests conducted, leading to a Type 2 error and the acceptance of hypotheses that were likely false [2].
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23

Wang, Kay Yee. "Mycoplasma pneumoniae and Bordetella pertussis in patients with persistent cough in primary care." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:74b15a97-708d-4927-b0aa-ce802f4af2aa.

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Background: Persistent cough following an acute respiratory tract infection is a challenging and frequently encountered problem in primary care. Mycoplasma pneumoniae (M. pneumoniae) and Bordetella pertussis (pertussis) particularly predispose patients to persistent cough. Whilst the incidence of M. pneumoniae is highest in children, pertussis may also occur in adults. Method: Four studies were conducted for this thesis. First, a systematic review to assess the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae. Second, a retrospective analysis of a cohort of children with persistent cough to assess the prognostic value of diagnosing M. pneumoniae. Third, a prospective cohort study to estimate the prevalence of M. pneumoniae and pertussis in children with persistent cough following recent changes in vaccination policy. Fourth, a double-blind randomised placebo-controlled trial to determine the effectiveness of montelukast in the treatment of persistent cough and pertussis-induced cough in adults. Results: M. pneumoniae and pertussis can each be found in one-sixth of children who present in primary care with persistent cough. Although coverage with the preschool pertussis booster vaccine is high, its efficacy wanes rapidly, with the likelihood of pertussis increasing by 30% per year after vaccination. Montelukast is not an effective treatment for persistent cough, but may be an effective treatment for pertussis-induced cough. Median duration of cough in children with M. pneumoniae is only one-third of that in children with pertussis (39 days versus 118 days). However, the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae is limited. Since M. pneumoniae occurs in cyclical epidemics, clinicians should consider current prevalence of M. pneumoniae when making a clinical diagnosis. Conclusions: Diagnosing M. pneumoniae and pertussis can help clinicians give patients an explanation for their cough and inform them about its likely prognosis. At the moment, clinicians should adopt a conservative approach to managing postinfectious persistent cough. A further trial is needed to assess the efficacy of montelukast for the treatment of pertussis-induced cough.
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24

Ruangdej, Kannika. "Acute effects of ambient ozone on a daily hospital admissions and daily mortality for respiratory and cardiovascular diseases among residents of Bangkok, Thailand." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/ruangdej.pdf.

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25

Blackley, David, Shimin Zheng, and Winn Ketchum. "Implementing a Weighted Spatial Smoothing Algorithm to Identify a Lung Cancer Belt in the United States." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etsu-works/42.

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Lung cancer is the leading cause of cancer death in the United States, but a large fraction of cases is preventable. We use a spatial smoothing algorithm to identify a geographic pattern of high lung cancer mortality, primarily in the Southeast, which we call a lung cancer belt. Disease belts are an effective mode for conveying patterns of high incidence or mortality; formally defining this lung cancer belt may encourage increased public dialogue and more focused research. Public health officials could complement existing population lung cancer data with this information to help inform resource allocation decisions.
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26

Bugajski, Andrew A. "BIOLOGICAL, BEHAVIORAL, AND PSYCHOSOCIAL ATTRIBUTES OF INDIVIDUALS WITH COPD." UKnowledge, 2018. https://uknowledge.uky.edu/nursing_etds/36.

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The purpose of this dissertation was to evaluate the biological, behavioral, and psychosocial attributes of individuals diagnosed with chronic obstructive pulmonary disease (COPD). Specific aims were to: 1) explore the predictive power of spirometry measures for event-free survival in patients with heart failure and suspected COPD, focusing on the differences in survival between those with and without airflow limitation; 2) examine the psychometric properties of the Multidimensional Scale of Perceived Social Support (MSPSS) in patients with concomitant COPD and heart failure; and 3) test the efficacy of a theory-based, multidimensional, self-care educational intervention using an eHealth platform on measures of symptom severity and variability, anxiety and depressive symptoms, perceived self-care ability, perceived self-care adherence, and selfcare information needs (knowledge) in a sample of adult patients with stable COPD. Specific aim one was addressed by evaluation of the predictive power of spirometry measures (forced expiratory volume/second [FEV1], forced vital capacity [FVC], and the ratio of FEV1/FVC) for event-free time to combined hospitalization/mortality after controlling for clinical and sociodemographic variables. This analysis revealed that those patients with airflow limitation were 2.2 times more likely to experience hospitalization/mortality compared to those without airflow limitation. The second specific aim was addressed with a psychometric evaluation of the Multidimensional Scale of Perceived Social support (MSPSS) which included determination of internal consistency reliability, the factor structure and construct validity by hypothesis testing in participants with comorbid COPD and heart failure. The MSPSS was a valid and reliable instrument to measure perceived social support in patients with comorbid COPD and heart failure. The third specific aim was addressed by a trial of an eHealth educational intervention in participants with COPD (N = 20). This intervention resulted in significant change in symptom severity evaluation in patients categorized as having medium symptom severity for the following symptoms: distress due to cough, chest tightness, dyspnea with activity and fatigue; these symptoms were perceived as more severe in the intervention period. Anxiety, depressive symptoms and perceived self-care ability were unchanged; however, perceived self-care adherence scores improved, and knowledge needs were significantly reduced after the intervention.
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27

Tacao, Guilherme Yassuyuki [UNESP]. "Impacto da exposição à queima de biomassa sobre a taxa de prevalência em doenças respiratórias e cardiovasculares na região de Presidente Prudente." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/152166.

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No. of bitstreams: 1 tacao_gy_me_prud.pdf: 2135735 bytes, checksum: 93545f4e3b7def501ab6778934b0c728 (MD5) Previous issue date: 2017-08-28<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>Introdução: A poluição atmosférica se tornou um importante problema de saúde pública a nível mundial e tem sido apontada como causa de impactos negativos na saúde humana. Esse impacto inclui aumento de mortalidade, de admissões hospitalares, de visitas à emergência e de utilização de medicamentos, devidas a doenças respiratórias e cardiovasculares. Objetivo: Essa dissertação teve como objetivos: analisar o impacto da exposição a poluentes atmosféricos nas doenças respiratórias e cardiovasculares na população adulta, além de investigar as doenças respiratórias nas crianças e adolescentes de uma cidade do sudoeste do estado de São Paulo moradores próximos a uma usina de cana-de-açúcar. Métodos: O estudo foi do tipo transversal, retrospectivo, de base populacional, utilizando-se de dados por meio de um Inquérito de Saúde para adultos e International Study of Asthma and Allergies in Childhood (ISAAC) em crianças e adolescentes, foram entrevistados no total 335 indivíduos. Os questionários foram aplicados diretamente à pessoa ou ao responsável para os menores de 12 anos. Foram utilizados os blocos temáticos de doenças respiratórias e cardiovasculares. Para assegurar a qualidade na coleta dos dados, foram realizadas entrevistas diretamente no domicílio por pesquisadores devidamente treinados. Para análise sanguínea foi analisado hemograma completo e glicemia de maneira que, fossem analisados níveis anormais para possível detecção de fatores de risco cardiovasculares. Conclusões: A exposição a queima de biomassa em moradores próximos a uma usina de cana de açúcar gerou impacto negativo no sistema respiratório nos moradores, tanto adultos quanto crianças moradoras do distrito, principalmente em mulheres e crianças.<br>Introduction: Air pollution is an important public health problem worldwide and has been cited as the cause of negative impacts on human health. This impact includes increased mortality, hospital admissions, emergency visits and medication use, due to respiratory and cardiovascular diseases. Objective: The objective of this dissertation was to analyze the impact of exposure to air pollutants on respiratory and cardiovascular diseases in the adult population, as well as to investigate respiratory diseases in children and adolescents living nearby a sugarcane factory in a city in the southwest of São Paulo. Methods: The study was a cross-sectional, retrospective, population-based study using data from an Adult Health Survey and International Study of Asthma and Allergies in Childhood (ISAAC) in children and adolescents, a total of 335 individuals were interviewed. The questionnaires were applied directly to the person or guardian for those under 12 years of age. Thematic blocks of respiratory and cardiovascular diseases were used. To ensure the quality of the data collection, interviews were conducted directly at the home by properly trained researchers. For blood analysis, complete blood count and glycemia were analyzed so that abnormal levels were analyzed for the possible detection of cardiovascular risk factors. Conclusions: Exposure to biomass burning in residents nearby a sugarcane plantation generated a negative impact on the respiratory system in residents, both adults and children living in the district, especially in women and children.<br>FAPESP: 15/14648-8
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28

Cross, Martyn. "Occupational respiratory health surveillance at Minara Resources, Murrin Murrin mine site." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2011. https://ro.ecu.edu.au/theses/418.

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This thesis outlines the results of occupational respiratory health surveillance at Minara Resources, Murrin Murrin mine site. The research was conducted as part of a collaborative agreement between Edith Cowan University and Minara Resources, the overarching title of which was ‗Establishing best practice protocols in the management of occupational and environmental health in a high-risk mining and ore-processing environment‘. To form the basis of this research it was hypothesised that although the chemical hazards had been adequately identified, and the occupational exposures in each work area at Murrin Murrin were generally well below their respective occupational exposure levels, it was still possible that additive, or even synergistic biological effects could cause adverse respiratory health effects due to the exposure to a combination of these atmospheric contaminants. This was the perception and a concern voiced by the Murrin Murrin workforce. Therefore, in working through the hypothesis, a literature review concentrating on the gaps in current knowledge and research for the early detection of occupational respiratory diseases was conducted, and the research tool and experiment design determined. The case for using pulmonary function tests in conjunction with a respiratory questionnaire in assessing early respiratory changes due to occupational exposures was established. Over a period between 17 February 2004 and 21 June 2006, a longitudinal study was conducted to ascertain the prevalence of respiratory symptoms and lung function of employees at the Murrin Murrin Operation, and compared with a local control group consisting of catering staff who resided at the accommodation camp approximately eight kilometres from the mine site. Lung function data were also compared to established predicted normal values from a reference population with normal lung function. Lung function data were analysed to determine whether there was an effect due to the area worked, and the employee‘s length of service. The lung function parameters of the study group, corrected for age and height were compared using linear regression analysis with both the control group and the predicted normal values. Repeat lung function tests were conducted on a sample of the original study group approximately two years after the initial study and statistically analysed to determine whether there was an effect on lung function over this time period. In addition, lung function tests were conducted for a cohort of refinery workers at the start and end of their two-week work period to determine whether there was a before-and-after effect due to their working conditions. The prevalence of respiratory symptoms was less in the study group compared to the controls; and these respiratory symptoms were determined to be non-work-related. On statistical analysis, for the ‗presumed healthy‘ workers (minus the smokers and those with known non-work-related respiratory symptoms) there was no overall decrement in lung function. Similarly, there was no overall statistically significant decrement in lung function for the ‗presumed healthy‘ workers in the repeat study conducted approximately two years after the initial study. There was no decrement in lung function associated with area work; nor was there a decrement in lung function for the cohort of refinery workers from the start to completion of their two-week work period. However, there were decrements in lung function for the smokers in the study and control groups. There was a significant difference in FEV1 between non-smokers and smokers with length of service (p
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29

Jenkins, Bradlee A., and L. Lee Glenn. "Miglustat Effects on the Basal Nasal Potential Differences in Cystic Fibrosis." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/7490.

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A recent study by Leonard, Lebecque, Dingemanse, and Leal [1] tested the effect of Miglustat, an alpha inhibitor on the cystic fibrosis conductance regulator gene using total chloride secretion in the nasal epithelium as the key variable estimated from basal nasal potential differences. The conclusion was drawn that “There was no evidence of a treatment effect on any nasal potential difference variable.” This conclusion may not be correct because of a slight misinterpretation of their statistical results. There also is a question of whether longer exposure periods than 8 days would have produced a more pronounced effect.
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30

Jenkins, Bradlee A., and L. Lee Glenn. "Effect of Asthma on Morbidity in Cystic Fibrosis." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/7554.

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31

Jenkins, Bradlee A., and L. Lee Glenn. "Morbidity Indicators of Asthma in Cystic Fibrosis." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/7555.

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32

Hugg, T. (Timo). "Exposure to environmental tobacco smoke, animals and pollen grains as determinants of atopic diseases and respiratory infections." Doctoral thesis, University of Oulu, 2009. http://urn.fi/urn:isbn:9789514291968.

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Abstract Little is known about a) the differences in allergic and respiratory diseases between the Finnish and Russian populations, and the environmental factors associated with those differences, and b) exposure to pollen grains indoors and the efficiency of penetration of pollen from outdoor to indoor air. This thesis is based on a cross-sectional population-based epidemiological study conducted in Imatra (Finland) and Svetogorsk (Russia) in 2003 and a rotorod-type-sampler-based pollen study conducted in the province of South Karelia (Finland) between 2003 and 2004. The prevalence of allergic diseases was higher among Finnish than Russian schoolchildren. The symptoms among allergic children were more severe, and the occurrence of respiratory infections was in general more frequent in Russia than in Finland. In the logistic regression analyses the risk of asthma was particularly related to high maternal smoking exposure, and the risk of the common cold was related to high combined parental smoking during infancy (adjusted OR 1.83, 95% CI 1.06–3.17) in Finnish children. Among Russian children, allergic conjunctivitis was related to maternal smoking, while the common cold was inversely related to paternal and parental smoking (0.60, 0.37–0.98 and 0.31, 0.11–0.83, respectively) during the study period. The risk of asthma was inversely related to any indoor dog-keeping in Finland (0.35, 0.13–0.95), whereas in Russia the risk of asthma was increased in relation to combined indoor cat exposure during infancy and the study period (4.56, 1.10–18.91). The concentrations of pollen grains decreased from abundant (0–855 pollen grains per cubic meter, pg/m3) to low (0–3 pg/m3), when moving from outdoors to indoors and further. The differences in diseases and symptoms in these two closely related populations could be ascribed to differences in culture, exposures, diagnostic criteria and treatment. The concentrations of pollen in indoor air during the flowering period were mostly on a level high enough to cause reactions in only the most sensitive subjects. The results suggest that more efforts should be directed to reducing parental smoking, to studying the role and effects of nationally different animal exposures in childhood, and to assessing the importance of different penetration routes of pollen grains<br>Tiivistelmä Suomen ja Venäjän välisistä allergioiden ja hengitystietulehdusten esiintymiseroista ja esiintymiseen vaikuttavista ympäristötekijöistä tiedetään varsin vähän. Myös tutkimuksia siitepölyille altistumisesta sisätiloissa ja siitepölyjen tunkeutumiskyvystä ulkoilmasta sisäilmaan on niukasti. Tutkimus yhdistää sekä lääketieteellisen että luonnontieteellisen tutkimusalan tutkimustraditiot sekä atooppisten sairauksien ja/tai hengitystietulehdusten tärkeimpien määrittäjien tarkastelun yhdeksi tutkimuskokonaisuudeksi. Väestö- ja kyselylomakepohjainen poikkileikkaustutkimus toteutettiin Suomen ja Venäjän rajan molemmin puolin sijaitsevissa Imatran ja Svetogorskin kaupungeissa vuonna 2003. Tutkimusväestö koostui 512 suomalaisesta ja 581 venäläisestä 7–16-vuotiaasta koululaisesta (osallistumisaste 79 %). Rotorod-tyyppisen keräimen käyttöön perustuva siitepölytutkimus toteutettiin erilaisissa ulko- ja sisätiloissa Lappeenrannan ja Imatran kaupungeissa, Rautjärven kunnassa ja valtatie 6:lla vuosina 2003 ja 2004. Atooppisten sairauksien esiintyvyys oli runsaampaa suomalaisten koululaisten keskuudessa. Sitä vastoin allergisten lasten kokemat oireet olivat voimakkaampia ja hengitystietulehdusten esiintyvyys oli runsaampaa venäläisten koululaisten keskuudessa. Astmariski kytkeytyi erityisesti äidin runsaalle tupakoinnille altistumiseen raskauden (vakioitu OR 3.51, 95 % luottamusväli 1.00–12.3), ensimmäisen elinvuoden (3.34, 1.23–9.07) ja tutkimuksen aikana (3.27, 1.26–8.48). Nuhakuumeen riski oli suurentunut suomalaisten koululaisten keskuudessa, jotka olivat altistuneet molempien vanhempien runsaalle tupakoinnille ensimmäisen elinvuoden aikana (1.83, 1.06–3.17). Äidin tupakoinnille ensimmäisen elinvuoden (4.53, 1.49–13.8) ja tutkimuksen aikana (2.82, 1.07–7.44) altistuneilla venäläisillä oli suurentunut allergisen silmän sidekalvotulehduksen riski. Tutkimuksen aikainen isän ja vanhempien tupakointi vähensi nuhakuumeen riskiä (0.60, 0.37–0.98; 0.31, 0.11–0.83) Venäjällä. Suomessa koiranpito sisätiloissa vähensi astmariskiä (0.35, 0.13–0.95), vastaavasti Venäjällä raskauden jälkeinen sisätiloissa tapahtuva kissa-altistus lisäsi koululaisten astmariskiä (4.56, 1.10–18.91). Siitepölyjen pitoisuudet pienenivät siirryttäessä ulkoa (0–855 siitepölyhiukkasta ilmakuutiossa; sp/m3) sisätiloihin (0–17 sp/m3). Ympäristöaltisteisiin ja sairauden ennusteeseen vaikuttavat sekä kansallinen kulttuuri ja vakiintuneet tavat, että erot diagnosointikriteereissä, yleisessä tautitietoisuudessa ja lääkkeiden saatavuudessa. Näin ollen altisteiden voimakkuus ja kesto sekä terveysvaikutukset voivat vaihdella merkittävästi lähellä toisiaan sijaitsevien alueiden välillä. Siitepölypitoisuudet sisätiloissa olivat pääosin tasolla, jolle altistuminen aiheuttaa oireita vain kaikkein herkimmille allergisille. Tutkimuksen tulosten mukaan lisää voimavaroja tulisi suunnata passiiviselle tupakoinnille altistumisen vähentämiseen erityisesti yksilökehityksellisesti herkkien varhaisvaiheiden aikana, kansallisten eläinaltistuserojen terveysvaikutusten selvittämiseen sekä siitepölyjen erilaisten kulkeutumisreittien merkityksen tutkimiseen
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33

Bradley, Jennifer L. "Obesity and Asthma: Adiponectin Receptor 1 (Adipo R1) and Adiponectin Receptor 2 (Adipo R2) are expressed by normal human bronchial epithelial (NHBE) cells at air-liquid interface (ALI) and expression changes with IL-13 stimulation." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4576.

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Obesity is recognized as an important risk factor for the development of many chronic diseases such as hypertension, Type 2 diabetes mellitus (T2DM) cardiovascular disease, cancer, renal disease, neurologic dysfunction, metabolic syndrome and asthma (3, 4). Circulating serum adiponectin levels in obese asthmatics have been reported to be low. Therefore, we aimed to investigate the role of adiponectin in a mucus hypersecretion model and hypothesized that adiponectin would decrease IL-13 induced MUC5AC expression from differentiated NHBE cells and that increasing concentrations of IL-13 would cause a decrease in Adipo R1 and Adipo R2 expression. MUC5AC expression with exposure to adiponectin was not significant. However, mRNA expression of Adipo R1 and Adipo R2 was significantly decreased by stimulation of IL-13 for acute (24 hours) and chronic (14 days) exposure. Therefore, the obese state and specifically IL-13 concentration could play a role in Adipo R1 and Adipo R2 expression within NHBE cells.
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34

Cruz, Belen A. "Oxygen Tension Modulates Growth Of Ovine Newborn Pulmonary Vascular Smooth Muscle Cells." Scholarship @ Claremont, 2014. http://scholarship.claremont.edu/scripps_theses/333.

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Background: Platelet activating factor (PAF) is a phospholipid synthesized by the action of phospholipase A2 and acetyl transferase. PAF possesses a wide range of biological activities. In the lung of the fetus and newborn, PAF binds to its G protein couple receptor to evoke its biological activities via a well-defined signaling pathway. High levels of PAF receptor (PAFr) activity in fetal ovine lung vascular smooth muscle cells (PVSMC) at baseline has previously been demonstrated, a finding that is further perpetuated by conditions of hypoxia similar to fetal lung environment. Additionally in fetal ovine PVSMC, a cross-talk between PAFr-mediated cell signaling and activity of the vasodilator cyclic nucleotides cGMP and cAMP acting via their respective receptors protein kinase (PK) G and PKA has been shown. The interaction of PAF with its receptor has been implicated in the pathogenesis of persistent pulmonary hypertension in the newborn (PPHN) which has a high incidence of hospitalization and death of newborn infants. Successful transition of fetus to newborn life entails a mechanism whereby vasoconstrictors necessary for fetal existence are abrogated in the immediate newborn. Hypothesis: We hypothesize that PPHN results from the failure to down regulate PAFr- mediated activity and /or failure to up-regulate activity of the vasodilators cGMP and cAMP. PPHN is triggered by chronic intrauterine or postnatal hypoxia. Then newborn PVSMC undergo hyperplasia and hypertrophy, which over time, results in irreversible vascular remodeling. Methods: My study aims to employ in vitro models to delineate the consequences of PAF-PAFr mediated pathway in the pharmacological effects of the cAMP-PKA and cGMP-PKG signaling and the involvement of this cross-talk in the pathogenesis of PPHN. I modeled my cell culture studies to mimic the low oxygen environment of fetal lungs (hypoxia), the normal oxygen environment of newborn lungs (normoxia) and high oxygen environment (hyperoxia) to which the newborn lung may be exposed in incidental clinical condition of PPHN. I studied the effect of PAF, a vasoconstrictor, cAMP/cGMP, vasodilators, and other inhibitors of the PAFr pathway on growth of newborn PVSMC, by DNA synthesis, and measured their effects on expression of mitogenic and non-mitogenic proteins. Results: We found that both hypoxia and hyperoxia decreased cell growth even in the presence of PAF which up-regulates cell growth in fetal PVSMC. Also PAF treatment of cells resulted in down regulation of the vasodilator proteins, PKA and PKG. Conclusion: Our data suggests that in the lung of the newborn a high activity of PAF-PAFr mediated activities will worsen the condition of PPHN imposed on the newborn lung by environmental or therapeutic conditions. We can speculate that, in the long run, these findings may translate into the establishment of less toxic protein-based management of PPHN.
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35

Härter, Martin, Harald Baumeister, Katrin Reuter, et al. "Increased 12-Month Prevalence Rates of Mental Disorders in Patients with Chronic Somatic Diseases." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-100021.

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Background: Although it is well established that chronic somatic diseases are significantly associated with a wide range of psychopathology, it remains unclear to what extent subjects with chronic somatic diseases are at increased risk of experiencing mental disorders. The present epidemiological study investigates age- and sex-adjusted 12-month prevalence rates of mental disorders in patients with cancer, and musculoskeletal, cardiovascular and respiratory tract diseases, based on comprehensive physicians’ diagnoses and compared with physically healthy probands. Methods: Prevalence rates were calculated from two large epidemiological surveys. These studies investigated inpatients and patients from the general population with cancer (n = 174) and musculoskeletal (n = 1,416), cardiovascular (n = 915) and respiratory tract diseases (n = 453) as well as healthy controls (n = 1,083). The prevalence rates were based on the Munich Composite International Diagnostic Interview, a standardized interview for the assessment of mental disorders. Results: Prevalence rates were very similar for inpatients (43.7%) and patients from the general population (42.2%). The adjusted odds ratios (OR) of patients with chronic somatic diseases were significantly elevated for mental disorders in comparison with healthy probands (OR: 2.2). Mood, anxiety and somatoform disorders were most frequent. The prevalence rates did not differ significantly between the somatic index diseases. The number of somatic diseases per patient had a higher association with mental disorders. Conclusions: There is a strong relationship between chronic somatic diseases and mental disorders. A future task is to improve the care of mental disorders in patients with chronic physical illness, specifically with multimorbid conditions.
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Fialho, Paula Mayara Matos 1983. "Estudo da associação entre toxocaríase, asma e obesidade em crianças de um bairro do município de Campinas-SP." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308559.

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Orientador: Carlos Roberto Silveira Correa<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas<br>Made available in DSpace on 2018-08-19T23:23:18Z (GMT). No. of bitstreams: 1 Fialho_PaulaMayaraMatos_M.pdf: 4006179 bytes, checksum: 3811feb02dfa10d8653c3dbcd13e9b40 (MD5) Previous issue date: 2012<br>Resumo: A associação entre toxocaríase, asma e aumento de peso ainda não foi estudada. Considerando-se que, provavelmente, haja diferenças entre os diversos fatores de risco para asma, assim como, o aumento de peso e levando-se em consideração que a toxocaríase é uma doença que acomete principalmente crianças, torna-se importante descrever a associação entre essas três variáveis. O objetivo deste trabalho foi estudar a associação entre toxocaríase, prevalência de asma e o sobrepeso e obesidade em crianças adscritas em uma Unidade Básica de Saúde (UBS) do município de Campinas, SP. Os resultados desta dissertação são apresentados no capítulo que engloba o artigo, Associação entre toxocaríase, asma e o índice de massa corporal em crianças, trata-se de um estudo transversal, realizado a partir de uma análise documental feita nos prontuários de 116 crianças atendidas na UBS do Jardim Santa Mônica em Campinas entre os anos 1996 a 1998. As seguintes informações foram obtidas dos prontuários: peso, altura, idade, sexo, presença ou não de asma, resultado do teste sorológico para Toxocara canis, presença ou não de eosinofilia. Para avaliação da antropometria foi usado os escores z. Para o estudo das associações entre presença de sorologia positiva para Toxocara canis, asma e IMC, foi utilizado o teste Wilcoxon para duas amostras. A amplitude da idade foi de 2 a 14 anos. Quanto ao sexo, 57,8% foram do sexo masculino. A prevalência de asma foi de 37,9% e a de crianças com sorologia positiva para infecção por T. canis foi de 54,3%. Comparando-se a distribuição z do IMC das crianças com sorologia positiva para infecção por T. canis com os das não infectadas, observou-se que os escores z mais elevados eram os das crianças com asma e com toxocaríase. Este trabalho aponta para a existência de uma associação entre a infecção por T. canis, asma e aumento do índice de massa corporal em crianças. A infecção por Toxocara tem associação com duas doenças de maior relevância na pediatria, a asma e a obesidade, as quais necessitam da atenção de todos os profissionais da saúde<br>Abstract: The association between toxocariasis, asthma and weight gain has not been studied. Considering that probably there are differences between the various risk factors for asthma, as well as weight gain and taking into account that toxocariasis is a disease that mainly affects children, it is important to describe the association between these three variables. The objective of this study was to investigate the association between toxocariasis and prevalence of overweight and obesity and asthma in children ascribed in a Health Basic Unit (UBS) in Campinas in São Paulo States. The results of this work are presented in the chapter that includes the article, "Association between toxocariasis, asthma and body mass index in children", it is a cross-sectional study from a documentary analysis made in the clinical reports of 116 children seen at UBS Jardim Santa Mônica in Campinas between the years 1996 to 1998. The following information was obtained from clinical reports: weight, height, age, sex, presence or absence of asthma, the serologic test for Toxocara canis, presence or not of eosinophilia. To evaluate the anthropometric z scores. To study the associations between positive serology for Toxocara canis, asthma and BMI, we used the Wilcoxon test for two samples. The age range was from 2 to 14 years. Regarding gender, 57.8% were male. The prevalence of asthma was 37.9% and children with positive serology for T. canis was 54.3%. Comparing the distribution of BMI z of children with positive serology for T. canis with those not infected, it was observed that the z-scores were higher for children with asthma and toxocariasis. This work points to the existence of an association between infection with T. canis, asthma and increased body mass index in children. Toxocara infection is associated with two diseases of major relevance in pediatrics, asthma and obesity, which require the attention of all health professionals<br>Mestrado<br>Epidemiologia<br>Mestre em Saude Coletiva
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37

Minagawa, Aurea Tamami. "Problemas respiratórios em crianças menores de dois anos e a reprodução social das famílias (estudo populacional no município de Itupeva SP)." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/7/7136/tde-23012008-102924/.

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A estreita relação entre saúde da criança e fatores sociais e econômicos é reconhecida há muito tempo, mas ainda a grande maioria das crianças pobres que adoece morre mais. Portanto, é necessário ampliar o conhecimento a respeito da rede de determinantes (distais, intermediários e proximais) dos problemas de saúde mais prevalentes nas crianças. As doenças respiratórias constituem uma das principais causas de morbidade e mortalidade infantil no Brasil e no mundo Justifica-se, pois, reconhecer os processos determinantes dos problemas respiratórios, considerando a determinação social do processo saúde-doença. Assim, os objetivos deste trabalho foram estimar a prevalência dos problemas respiratórios nos diferentes grupos sociais homogêneos; caracterizar como esses problemas se relacionam às formas de reprodução social das famílias e avaliar os determinantes proximais, intermediários e distais associados à sua ocorrência. Este estudo populacional transversal foi realizado no município de Itupeva (SP), numa amostra representativa de 261 crianças menores de dois anos. A partir de um modelo teórico hierarquizado, centrado na categoria da reprodução social, foram compostos os perfis de reprodução social, utilizando-se uma base teórico-metodológica-operacional que predefiniu três grupos sociais homogêneos (GSH): formas de trabalhar e de viver adequadas (GSH1); formas de trabalhar ou de viver adequadas (GSH2) e formas de trabalhar e de viver inadequadas (GSH3). Os problemas respiratórios foram detectados segundo informações obtidas por meio de inquérito recordatório do último mês. Associações foram verificadas pelo teste Qui-quadrado (variáveis categóricas) ou teste de Fischer, e teste t de Student (variáveis contínuas). Utilizou-se o modelo de regressão logística não condicional para a análise múltipla. Para evitar exclusão de variáveis importantes, utilizou-se um nível de significância de 0,20 e para indicar associação estatisticamente significativa, nível de 0,05. Na análise múltipla, as associações foram expressas em odds ratio e seu intervalo de confiança [IC] para 95%. A prevalência de problema respiratório foi de 71,6% (IC95% 65,8 - 77,0), sendo maior nos estratos inferiores, porém sem diferença estatisticamente significativa: 64,0% no GSH1, 75,8% no GSH2 e de 71,5% GSH3 (p>0,05). Com relação ao total da amostra, a escolaridade do pai se mostrou estatisticamente diferente entre as crianças que haviam apresentado problema respiratório e aquelas que não haviam apresentado: 56,1% dos pais das crianças com problemas respiratórios tinham menos de 7 anos de estudo, enquanto 62,9% dos pais das crianças sem problemas respiratórios tinham mais de 7 anos de estudo. A escolaridade materna seguiu a mesma tendência. A ocorrência de problemas respiratórios foi discretamente maior nas crianças do sexo feminino, e naquelas de 12 a 18 meses. A primeira etapa da regressão logística testou cada variável que se associou com a ocorrência de problemas respiratórios (p<0,20). A segunda etapa foi verificar em cada nível hierárquico (determinantes distais, intermediários e proximais), as variáveis que mantinham associação com a ocorrência de problemas respiratórios, quando analisadas em conjunto com as outras variáveis do mesmo nível. A terceira etapa incluiu, no modelo, os determinantes distais (variáveis sociodemográficas e de trabalho do chefe) e intermediários (formas de viver). Nessa fase, o modelo selecionou, como significativamente associadas com a ocorrência de problemas respiratórios, a escolaridade do pai e a ventilação da casa. Variáveis essas que permaneceram na quarta etapa, em que se incluíram os determinantes proximais (características infantis e de atendimento à saúde). Permaneceram significativamente associadas à ocorrência de problemas respiratórios, até a última etapa do modelo hierarquizado, a escolaridade do pai e a idade da criança, o que demonstra a importância dos determinantes distais no desfecho do processo saúde-doença. Embora a melhoria nas formas de trabalhar e de viver das famílias aparentemente não seja atribuição de profissionais de saúde, uma vez que se atrelam a transformações estruturais, estes são responsáveis pela conscientização da população e sua mobilização em torno de objetivos comuns, em busca de uma melhor integração social<br>The close relation between children\'s health and socioeconomics factors is recognized for a long time; however, even so the most majority of poor children which become sick die more than others. Therefore, it\'s necessary to enlarge de knowledge about the determinants (distal, intermediate and proximal) of most prevalent children\'s health problems. Respiratory disease is one of the main causes of infant morbidity and mortality in Brazil and in the world. So it\'s justified to recognize the processes that determine the respiratory problems, considering the social determination of health-disease process. Thus, this work aimed to estimate the prevalence of respiratory problems at different homogeneous social groups; to characterize how these problems are related to social reproduction of families and to evaluate the proximal and distal determinants related to their occurrence. This transverse population study was carried out at the city of Itupeva (São Paulo, Brazil), with a representative sample of 261 children under 2 years old. Based on a hierarchical theoretical model, focused on social reproduction, the profiles of social reproduction were composed by using an operationalmethodological- theoretical basis that pre-defined three homogeneous social groups (HSG): proper ways of working and living (HSG1), proper ways of working or living (HSG2); improper ways of working and living (HSG3). The respiratory problems were detected through information got from the remainder inquiry of the last month. Associations were observed through Chi-square test (scaled variables) or Fischer Test, and Student t-test (continuous variables). The non-conditional logistic regression model was used to accomplish the multiple analyses. In order to avoid exclusion of important variables, it was used a significance level of 0.20, and a level of 0.05 was used to indicate a statistically significant association. At the multiple analysis, the association were expressed by odds ratio (OR) and their confidence interval (CI) to 95%. The prevalence of respiratory problem was 71.6% (CI95% 65.8 - 77), being greater at inferior layers, but without a statistically significant difference: 64.0% at HSG1, 75.8% at HSG2 and 71.5% at HSG3 (p>0.05). With regard to the total of sample, father\'s schooling level has showed to be statistically different among children which have presented respiratory problem and children which not presented: 56.1% of fathers (children with respiratory problems) have less than seven years of schooling, while 62.9 of fathers (children without respiratory problems) have more than seven years of schooling. Mother\'s schooling follows the same tendency. The occurrence of respiratory problems was a little bigger to female children and to those with ages among 12-18 months. The first step of logistic regression has tested each variable associated with the occurrence of respiratory problem (p<0.20). The objective of the second step was to check in each hierarchical level (distal, intermediate and proximal determinants) the variables that kept an association with the occurrence of respiratory problems when analyzed together with others of the same level. The third step has included (in the model) the distal determinants (socialdemographics variables and work of household variables) and intermediate determinants (ways of living). At this stage, the model has chosen, as significantly related to respiratory problems, the father\'s schooling level and the house ventilation. These variables have remained in the fourth step, and in these same step it has been included the proximal determinants (infant characteristics and health care). Also the father\'s schooling level and children\'s age have remained significantly associated to until the last step of the model respiratory problems; this demonstrates the importance of the distal determinants in the conclusion of the process health-disease. Although the improvement of the ways of working and living of the families appear not to be part of attributions of health professionals (once these ways are linked to structural transformations), they are responsible to aware and mobilize the population around a common objective, that is a better social integration
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38

Muchão, Fabio Pereira. "Avaliação da eficácia e segurança de doses crescentes de salbutamol, administrado através de inalador dosimetrado, em crianças e adolescentes com crise de asma." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-06022017-151909/.

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INTRODUÇÃO: A dosagem ideal de salbutamol através de inaladores dosimetrados para o tratamento da asma aguda na infância não está bem estabelecida. Este estudo visou comparar dois regimes de dosagem de salbutamol via inalador dosimetrado com espaçador em crianças com crises moderadas ou graves de asma. As hipóteses deste estudo foram: I. Pacientes em vigência de crises de sibilância moderadas ou graves necessitam doses de salbutamol maiores que as até recentemente recomendadas pelo Global Initiative for Asthma (GINA). II. Doses maiores de salbutamol são seguras para crianças com idade igual ou superior a dois anos de idade. OBJETIVOS: I. Avaliar a eficácia (principalmente tempo de permanência na sala de emergência e taxas de internação hospitalar) de um regime de doses maiores de salbutamol em comparação com as até recentemente recomendadas pelo GINA. II. Verificar a segurança destas dosagens de salbutamol através do monitoramento de possíveis efeitos colaterais e dos níveis plasmáticos desta droga. MÉTODOS: Este foi um estudo prospectivo, randomizado, duplo-cego e controlado realizado em salas de emergência de três centros na cidade de São Paulo. Foram incluídos pacientes com 2-17 anos de idade com asma aguda moderada a grave (escore PRAM, Pediatric Respiratory Assessment Measure, >= 5). As dosagens de salbutamol via inalador dosimetrado com espaçador administradas durante a primeira hora foram: 6 (até 25 kg) ou 12 jatos ( > 25 kg) no grupo controle e 9 (até 15 kg), 12 ( > 15 a 20 kg), 15 ( > 20 a 25 kg) ou 18 jatos ( > 25 kg) no grupo estudo. Cada jato continha 100 mcg de salbutamol. Os pacientes dos dois grupos receberam corticosteroides e brometo de ipratrópio. Os desfechos principais do estudo foram o tempo de permanência na sala de emergência para os pacientes não internados e a necessidade ou não de internação hospitalar. Os desfechos secundários foram: mudança no volume expiratório forçado no primeiro segundo (VEF1) após uma hora, mudanças no escore PRAM, na oximetria de pulso e na frequência respiratória após uma hora e no tempo final (momento da alta ou internação hospitalar, máximo de quatro horas) e a necessidade de tratamentos adicionais após a primeira hora. Os desfechos de segurança incluíram mudanças nos níveis séricos de potássio, glicose, bicarbonato e pH no tempo final em relação ao tempo inicial, bem como possíveis anormalidades no eletrocardiograma, níveis plasmáticos de salbutamol, mudanças na frequência cardíaca e presença ou ausência de tremores, os dois últimos após uma hora e no tempo final. RESULTADOS: Foram incluídos 119 pacientes com condições basais semelhantes e não foram observadas diferenças significativas entre os grupos no tempo de permanência na sala de emergência (p=0.55) ou nas taxas de internação hospitalar (p=0.48). Não foram observadas diferenças significativas entre os grupos nas mudanças de VEF1 após uma hora, nas mudanças de escore PRAM, na oximetria de pulso e na frequência respiratória após uma hora e no tempo final. Não houve diferenças significativas entre os grupos na necessidade de tratamentos adicionais administrados após a primeira hora. Não foram observadas diferenças significativas nos desfechos de segurança entre os grupos. CONCLUSÕES: O uso de doses maiores de salbutamol administradas através de inalador dosimetrado com espaçador em crianças com asma aguda moderada ou grave não resultou em menor taxa de internação, menor tempo de permanência na sala de emergência ou melhora em outros desfechos de eficácia em comparação com o regime de dosagens até recentemente proposto pelo GINA. Os dois regimes de dosagens mostraram perfis de segurança semelhantes<br>INTRODUCTION: The ideal dosing of albuterol via metered-dose inhalers for acute childhood asthma is not well established. This study aimed to compare two dosing regimens of albuterol via metered-dose inhaler with spacer in children with moderate to severe asthma attacks. The hypothesis of this study were: I. Patients with moderate to severe asthma attacks would benefit from higher doses of albuterol than those recommended until recently by the Global Initiative for Asthma (GINA). II. Higher doses of albuterol are safe for children two years of age and older. OBJECTIVES: I. To compare the efficacy (mainly length of stay in the emergency room and admission rates) of higher doses of albuterol with those recommended until recently by the GINA. II. To assess the safety of different doses of albuterol by monitoring for possible side effects and measuring drug plasma levels. METHODS: This was a prospective, randomized, controlled, double-blind study conducted in emergency rooms of the three participating centers in the city of São Paulo. We included patients with 2-17 years old with moderate to severe acute asthma (Pediatric Respiratory Assessment Measure, PRAM, score >= 5). Dosages of albuterol via metered-dose inhaler with spacer administered during the first hour included: 6 (up to 25 kg) or 12 puffs ( > 25 kg) in the control group and 9 (up to 15 kg), 12 ( > 15 to 20 kg), 15 ( > 20 to 25 kg) or 18 puffs ( > 25 kg) in the study group. Each puff contained 100 mcg of albuterol. All patients received corticosteroids and ipratropium bromide. Primary outcomes were the length of stay in the emergency room for non-admitted patients, and rate of admission. Secondary outcomes included forced expiratory volume in one second (FEV1) changes following one hour, PRAM score, pulse oximetry and respiratory rate changes following one hour and at the final time (discharge or admission, maximum four hours) and the need for additional therapies after the first hour. Safety outcomes included changes in serum potassium, glucose, bicarbonate and pH at the final time in comparison with the initial time, as well as electrocardiogram abnormalities, plasma albuterol levels, heart rate, and tremors (the last two after one hour and at the final time). RESULTS: We included 119 patients with similar baseline conditions, and no significant differences were observed between groups in the length of stay in the emergency room (p=0.55) or admission rates (p=0.48). No significant differences were observed between groups in FEV1 changes after one hour, and PRAM score, pulse oximetry and respiratory rate changes after one hour and at the final time. There were no significant differences between groups in additional therapies administered after the first hour. No significant differences were observed in safety outcomes between groups. CONCLUSIONS: Higher dosage regimens of albuterol via metered-dose inhaler with spacer for children with moderate to severe acute asthma did not result in lower admission rate, shorter length of stay in the emergency room or improvement in other efficacy outcomes in comparison with those recommended until recently by the GINA. Both dosage regimens showed similar safety profile
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39

Karandashova, Sophia. "The Role of Ceramide in Neutrophil Elastase Induced Inflammation in the Lungs." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5468.

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Alterations to sphingolipid metabolism are associated with increased pulmonary inflammation, but the impact of inflammatory mediators, such as neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. NE is a protease associated CF lung disease progression, and can be found in up to micromolar concentrations in patient airways. While sphingolipids have been investigated in the context of CF, the focus has been on loss of cystic fibrosis transmembrane conductance regulator (CFTR) function. Here, we present a novel observation: oropharyngeal aspiration of NE increases airway ceramides in mice. Using a previously characterized mouse model of NE-induced inflammation, we demonstrate that NE increases de novo ceramide production, which is likely mediated via increased SPTLC2 levels. Inhibition of de novo sphingolipid synthesis using myriocin, an SPT inhibitor, decreases airway ceramide as well as the release of pro-inflammatory signaling molecules induced by NE. Furthermore, in a retrospective study of the sphingolipid content of CF sputum—the largest of its type in this patient cohort to date, we investigated the association between NE and sphingolipids. There were linear correlations between the concentration of active NE and ceramide, sphingomyelin, and monohexosylceramide moieties as well as sphingosine-1-phosphate. The presence of Methicillin-resistant Staphylococcus aureus (MRSA) positive culture and female gender both strengthened the association of NE and sphingolipids, but higher FEV1 % predicted weakened the association, and Pseudomonas aeruginosa had no effect on the association between NE and sphingolipids. These data suggest that NE may increase sphingolipids in CF airways as it did in our in vivo model, and that this association is stronger in patients that have worse lung function, are female, and whose lungs are colonized with MRSA. Modulating sphingolipid homeostasis could provide novel pharmacological approaches for alleviating pulmonary inflammation.
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40

Main, Carey Anne. "To determine the relationship between dietary intake, body composition and incidence of upper respiratory tract infections in triathletes during training and competition for the Ironman." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/80006.

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Thesis (MNutr)--Stellenbosch University, 2013.<br>ENGLISH ABSTRACT: Background: The Ironman® triathlon is an ultra-endurance event. It has previously been shown that heavy training schedules and racing ultra-endurance events can lead to immune impairment. Evidence supporting the potential role of dietary intake and body composition on immune impairment or upper respiratory tract infections (URTIs) is currently lacking. Aim: To investigate the relationship between dietary intake, body composition and the incidence of URTI in triathletes residing in Port Elizabeth (PE), during training and competition for the Ironman® 2011 triathlon. Method: An observational longitudinal descriptive study with an analytical component was conducted. The study population included triathletes living in PE, who completed an Ironman® distance event one year prior to, and who were training for the April 2011 Ironman®. Habitual dietary intake was assessed with a quantitative food frequency questionnaire; and race dietary strategies with a three day food record. Body composition was determined with anthropometry and the incidence of URTI was assessed with the WURSS-44. A general health screen (SF-36) was also administered. Results: Habitual dietary intake during the three months pre- and post-Ironman® 2011 triathlon was adequate for all nutrients except for carbohydrate intake in female and male participants (pre-Ironman® of 4.0 (1.7) g/kg body weight (BW)/day and 5.4 (1.8) g/kg BW/day; and post-Ironman® 3.0 (1.0) g/kg BW/day and 4.7 (1.5) g/kg BW/day respectively). Carbohydrate-loading strategies were below recommendations with intakes of 6.0 (2.9) and 5.1 (2.5) g/kg BW/day for female and male participants respectively. Race day nutrition strategies were below recommendations for carbohydrate intake. Post-race dietary intake was below recommendations for carbohydrate in the female participants (0.9 (0.5) g/kg BW). Body mass index was 26.6 (3.4) kg/m2 and 26.1 kg/m2 (1.40) for female and male study participants respectively. Body fat percentage was at the upper end for endurance athletes (29.3 (9.4) % and 13.7 (5.1) % for females and males respectively). In this study 25 % of the triathletes (N=20) developed an episode of URTI during the 3 months post-Ironman®. Dietary intake parameters measured three months pre-Ironman® that had a significant influence on URTI were: potassium (p=0.04) and thiamine (p=0.02) and dietary intake parameters measured 3 months post-Ironman® that had a significant influence on URTI were: total protein (p=0.04); isoleucine (p=0.03); leucine (p=0.03); phenylalanine (p=0.03); valine (p=0.02); thiamine (p=0.01); and Beta-tocopherol (p=0.03). Dietary intake parameters measured during the race that had a significant influence on URTI were: selenium (p=0.04); folate (p=0.04) and proline (p=0.02). Body composition did not have a significant influence on URTI. Conclusion: Habitual dietary intake three months pre- and post-Ironman® as well as pre- and post Ironman race strategies were low for carbohydrate. Body composition indicated that athletes were at the upper end associated with endurance sport. There was a relationship found between an episode of URTI and dietary intake.<br>AFRIKAANSE OPSOMMING: Agtergrond: Die Ironman® driekamp is 'n ultra-uithouvermoë kompetisie. Daar is voorheen bewys dat swaar oefening skedules en ultra-uithouvermoë kompetisies kan lei tot ‘n immuungebrek. Daar is tans ‘n tekort aan wetenskaplike bewyse wat die potensiële rol van dieetinname en liggaamsamestelling op immuungebrek of boonste lugweginfeksies ondersoek. Doel: Die doel van die studie was om ondersoek in te stel oor die verhouding tussen dieetinname, liggaamsamestelling en die insidensie van boonste lugweg infeksies in driekamp atlete woonagtig in Port Elizabeth (PE), tydens oefening en deelname aan die Ironman® 2011 driekamp. Metodes: 'n Waargenome, longitudinale beskrywende studie is gedoen met 'n analitiese komponent. Die studiepopulasie het bestaan uit driekampatlete woonagtig in PE, wat 'n Ironman® afstand kompetisie voltooi het een jaar voor en wat oefen vir die April 2011 Ironman® kompetisie. Gewoontelike dieetinname is bepaal met 'n kwantitatiewe voedselfrekwensie vraelys, en dieet strategieë rondom die byeenkoms met 'n drie dag voedselrekord. Liggaamsamestelling is bepaal met antropometrie en die insidensie van boonste lugweg infeksies is bepaal met die WURSS-44. 'n algemene gesondheid vraelys (SF- 36) is ook ingevul. Resultate: Die gewoontelike dieetinname gedurende die drie maande voor- en na-Ironman® 2011 was voldoende vir alle voedingstowwe, behalwe vir koolhidraat-inname in die vroulike en manlike deelnemers (voor Ironman® 4.0 (1.7) g / kg liggaamsmassa (LM) / dag en 5.4 (1.8) g / kg LM / dag, en na Ironman® 3.0 (1.0) g / kg LM / dag en 4.7 (1.5) g / kg LM / dag onderskeidelik). Koolhidraatlading strategieë was ontoereikend met innames van 6.0 (2.9) en 5.1 (2.5) g / kg BW / dag vir vroulike en manlike deelnemers onderskeidelik. Die inname op die dag van die byeenkoms was onvoldoende vir koolhidraat. Die dieetinname na die byeenkoms was onvoldoende vir koolhidraat inname in die vroulike deelnemers (0.9 (0.5) g / kg LM). Die liggaamsmassa-indeks was 26.6 (3.4) kg/m2 en 26.1 (1.4) kg/m2 vir vroulike en manlike deelnemers onderskeidelik. Persentasie liggaamsvet was aan die boonste grens geassosieer met uithouvermoë oefening atlete 29.3 (9.4) % en 13.7 (5.1) % vir vrouens en mans onderskeidelik. Die insidense van boonste lugweg infeksies was 25% (N=20) gedurende die drie maande na Ironman®. Dieetinname paramters wat gemeet was drie maande voor Ironman® wat beduidende beïnvloed met boonste lugweginfeksies getoon het, was, kalium (p=0.04) en tiamien (p=0.02) en die dieetinname parameters wat drie maande na Ironman® gemeet is en betekenisvolle beïnvloed getoon het met boonste lugweginfeksies was, totale proteïen (p=0.04); isoleusien (p=0.03), leusien (p=0.03), fenielalanien (p=0.03), valien (p=0.02), tiamien (p=0.01), en B-tocopherol (p=0.03). Die dieetinname parameters wat gemeet was tydens die wedloop wat beduidende beïnvloed met boonste lugweginfeksies getoon het na Ironman® 2011 was, selenium (p=0.04), folaat (p=0.04) en prolien (p=0.02). Die antropometriese parameters gemeet het nie beïnvloed op boonste lugweginfeksies gehad nie. Gevolgtrekking: Die gewoontelike dieetinname drie maande voor- en na Ironman® sowel as voor- en na Ironman® kompetisie strategieë was onvoldoende vir koolhidrate. Liggaamsamestelling het aangedui dat atlete aan die boonste grens geassosieer met uithouvermoë oefening geval het. Daar was beduidende beïnvloed gevind tussen dieetinname en boonste lugweginfeksies.
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41

Mohammed, Bassem M. "Vitamin C: A potential regulator of inflammatory response." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3699.

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Introduction: Neutrophils (PMNs) and Macrophages are the first responders recruited consecutively to the site of injury/inflammation. PMNs’ response/fate as well as macrophage reprogramming ultimately determine the course of resolution of inflammation. Physiologic wound healing has a significant inflammatory component. An exaggerated inflammation however is self-defeating leading to delayed healing. Parenteral vitamin C (VitC) attenuated inflammation in murine sepsis models and in patients with sepsis. However information about the mechanisms by which VitC regulates these events is limited. Methods: Humanized mice lacking VitC synthesis capability (Gulo-/-) were used. VitC sufficient and deficient mice were challenged with sterile inflammation, or septic insults. Some VitC deficient mice received parenteral VitC (200mg/kg) following the challenge to give deficient + AscA mice up to 14 days. Using a murine model of excisional wound, two full thickness excisional wounds were created on the back of the different Gulo-/- mice groups. Wound tissues were excised at day 7 and 14 post-wounding for analysis. Cell counts, immunohistochemistry, circulating free DNA, the expression of pro- and anti-inflammatory proteins were investigated. Additional in vitro experiments were carried out using human PMN (huPMNs), THP-1 monocyte/macrophage, and neonatal human dermal fibroblasts (HnDF). Results: VitC deficiency delayed resolution of lung inflammation and led to exaggerated pro-inflammatory responses. PMNs from VitC deficient mice demonstrated increased autophagy, histone citrullination, and NFκB activation, while inhibiting apoptosis. VitC sufficiency/supplementation restored macrophage phenotype, as well as attenuated neutrophil extracellular trap (NET) formation. VitC attenuated pro-inflammatory responses in THP-1 macrophages. In wound healing model, wounds from VitC sufficient/AscA infused mice had lower gene expression of the pro-inflammatory mediators; higher expression of genes promoting wound healing and resolution. Exposure of HnDF to AscA increased their intracellular VitC levels; promoted fibroblast proliferation and induced expression of fibroblast self-renewal genes. Conclusion: Our findings identify VitC as a novel regulator of PMN and macrophage responses. In wound healing, VitC favorably impacted the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodeling. Collectively, these results substantiate the protective notion of parenteral VitC and support its clinical use.
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42

Chuc, Nguyen Thi Kim. "Towards good pharmacy practice in Hanoi : a multi-intervention study in private sector /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-316-3.

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43

Smith, Eliot T. "Bioengineering the Expression of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, and C-Reactive Protein in Yeast." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etd/1198.

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The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human cathepsin G (hCatG) and human neutrophil elastase (HNE) were expressed in P. pastoris and HNE was also expressed in K. lactis. The recombinant variants rhCatG and rHNE, with intact C-terminal extensions, were expressed as fusion proteins with the soluble heme-binding domain of cytochrome B5 (CytB5) and an N-terminal hexahistidine (6xHis) tag for purification. The CytB5 domain was linked to the native N-termini of active rhCatG and rHNE by the EPLcleavable substrate sequence DDDDK~I, where ~ is the sessile bond. These fusion proteins were directed for secretion. The yeast P. pastoris expressed up to 3.5 mg/L of EPL-activable rHNE in fermentation broth; however, only 200 μg/L of rhCatG could be produced by this method. Recombinant expression in K. lactis never surpassed 100 μg/L of activable rHNE. The CytB5 fusion domain was present in the heme-bound form, conferring a red color and 410 nm absorbance peak to solutions containing the fusion proteins. This absorbance pattern was most readily visible during the purification of CytB5-rHNE from P. pastoris. Human C-reactive protein (hCRP) and the substitution variant CRP E42Q were expressed in recombinant form and secreted by P. pastoris. Both products were found to bind phosphocholine (PCh) in the same manner as native hCRP. Difficulties encountered during purification revealed that wild type recombinant CRP (rCRP) was produced at 2 different molecular masses. The P. pastoris recombinant expression system yielded better results than K. lactis. Bioreactor-scale fermentation in a 5 L vessel facilitated expression and characterization of these recombinant proteins.
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44

Härter, Martin, Harald Baumeister, Katrin Reuter, et al. "Increased 12-Month Prevalence Rates of Mental Disorders in Patients with Chronic Somatic Diseases." Karger, 2007. https://tud.qucosa.de/id/qucosa%3A26278.

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Background: Although it is well established that chronic somatic diseases are significantly associated with a wide range of psychopathology, it remains unclear to what extent subjects with chronic somatic diseases are at increased risk of experiencing mental disorders. The present epidemiological study investigates age- and sex-adjusted 12-month prevalence rates of mental disorders in patients with cancer, and musculoskeletal, cardiovascular and respiratory tract diseases, based on comprehensive physicians’ diagnoses and compared with physically healthy probands. Methods: Prevalence rates were calculated from two large epidemiological surveys. These studies investigated inpatients and patients from the general population with cancer (n = 174) and musculoskeletal (n = 1,416), cardiovascular (n = 915) and respiratory tract diseases (n = 453) as well as healthy controls (n = 1,083). The prevalence rates were based on the Munich Composite International Diagnostic Interview, a standardized interview for the assessment of mental disorders. Results: Prevalence rates were very similar for inpatients (43.7%) and patients from the general population (42.2%). The adjusted odds ratios (OR) of patients with chronic somatic diseases were significantly elevated for mental disorders in comparison with healthy probands (OR: 2.2). Mood, anxiety and somatoform disorders were most frequent. The prevalence rates did not differ significantly between the somatic index diseases. The number of somatic diseases per patient had a higher association with mental disorders. Conclusions: There is a strong relationship between chronic somatic diseases and mental disorders. A future task is to improve the care of mental disorders in patients with chronic physical illness, specifically with multimorbid conditions.
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45

Rahman, Anisur. "Prenatal Arsenic Exposure and Consequences for Pregnancy Outcome and Infant Health : Epidemiological Studies in Bangladesh." Doctoral thesis, Uppsala universitet, Internationell mödra- och barnhälsovård (IMCH), 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-100770.

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The aim of this thesis was to analyse possible effects of prenatal arsenic exposure on foetal and infant health. The setting is Bangladesh, where two cohorts were studied, both part of a health and demographic surveillance system in Matlab. A historical cohort 1991-2000 included 29,134 pregnant women with information on drinking water sources and arsenic testing of tube well water. A prospective cohort study included pregnant women 2002 - 2003 where urinary arsenic concentrations were assessed twice during pregnancy; 2,924 women and their pregnancy outcomes were evaluated for foetal loss, perinatal and infant mortality; 1,578 mother-infant pairs were analysed for size at birth; and 1,552 were analysed for morbidity during infancy. Women exposed to arsenic levels ≥ 50 µg/L in water had an increased risk of foetal loss and infant death in comparison with women exposed to arsenic levels &lt; 50 µg/L. These findings were confirmed in the prospective cohort study. Women with urine arsenic concentrations at the 5th quintile had 62% increased risk of spontaneous abortion (OR 1.62, 95% CI 1.04 - 2.55) in comparison with women who had arsenic concentrations at the 1st quintile level. Increased risks of perinatal morality (RR 3.01, 95% CI 1.07 - 8.45) and infant mortality (RR 5.01; 95% CI: 1.41 - 17.84) were also observed at the 5th quintile of exposure. Significant negative dose-effect associations were found between arsenic exposure and birth weight, head and chest circumferences at a relatively low level of exposure (&lt;100 µg/L in urine). In this range of exposure birth weight decreased by 1.68 g (SE 0.62) for each 1 µg/L increase of arsenic in urine. In comparison with exposure at the 1st quintile level the risk of lower respiratory tract infection was significantly increased (RR 1.68, 95% CI 1.35-2.07) for women who had urinary arsenic concentrations at the 5th quintile level. The risk was also increased for diarrhoeal diseases. The study findings highlight the negative effects of arsenic exposures on pregnancy outcomes and infant health. Mitigation programs need to be strengthened and women of reproductive ages should be prioritized in arsenic affected regions worldwide.
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46

Dunn, Melissa A. "Childhood Asthma: Contextual Influences Affecting Family Management." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsn_diss/64.

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Purpose: The purpose of this study was to explore the way(s) in which family management of childhood asthma is affected by contextual influences as described in the Family Management Style Framework (FMSF) and to explore additional factors that affect family asthma management. Specific Aims: The specific aims of this study were 1) to describe the everyday experiences of childhood asthma management within families, 2) to explore the way(s) in which family management of childhood asthma is affected by contextual influences (social network, care providers & systems and resources) as described in the FMSF, and 3) to explore additional sociocultural factors (supported by the literature but not currently described in the FMSF) that affect asthma management in families. Framework: The Family Management Style Framework guided this study. Design: A qualitative descriptive design was used to gather data from a purposive sample of female primary caregivers. Demographic data were collected, and individual interviews were conducted using a flexible interview guide. Results: The findings support the contextual influences as described in the FMSF. An additional three contextual themes were identified: environment, emerging threats to health and work-life conditions. The themes are interrelated demonstrating the complexity of asthma management. Conclusion: Family management of asthma is challenging and complex. The findings move towards understanding the connection between family asthma management and the social determinants of health. Nurses can support families managing childhood asthma by considering each of the contextual influences when planning interventions and working on policy initiatives that support the health of children with asthma.
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47

Gruntman, Alisha. "A Translational Pathway for Recombinant Adeno-Associated Virus Human Gene Therapy: From Target Identification and Animal Modeling of the Disease to Non-Human Primate and Human Studies." eScholarship@UMMS, 2011. http://escholarship.umassmed.edu/gsbs_diss/882.

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Many steps go into developing a clinical viral gene therapy. The course starts with appropriate disease selection and moves through the many hurdles of in-vitro testing, animal model validation and proof-of-concept studies, all the way through pre-clinical large animal studies. In this thesis, I propose to outline the process of developing a translation pathway for a gene therapy using recombinant adeno-associated virus (rAAV). I will expand on this outline using data that I have generated during the course of my Ph.D. that ranges from animal model validation all the way through pre-clinical vector stability studies. Two disease models will be discussed throughout this thesis, Cockayne Syndrome (CS) and Alpha-1 Antitrypsin Deficiency (AATD). Cockayne Syndrome is a rare autosomal recessive genetic disorder involving mutations in either the CSA or CSB gene, leading to defects in DNA repair. Clinically this presents as progressive degeneration of the central nervous system, retina, cardiovascular system, and cochlea, which leads to mental retardation, post-natal growth defects, ocular abnormalities, and shortened life expectancy. Alpha-1 antitrypsin is a serine protease inhibitor largely produced in the liver that mainly functions to inhibit neutrophil elastase within the lung. AATD leads to an increased risk of emphysema, with shortened life expectancy, and also results in accumulations of mutant AAT polymers in the liver, sometimes leading to liver failure. Using these two disease models I will outline the upstream and downstream pre-clinical work as well as the transition to clinical trials of a rAAV based gene therapy.
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48

Gruntman, Alisha. "A Translational Pathway for Recombinant Adeno-Associated Virus Human Gene Therapy: From Target Identification and Animal Modeling of the Disease to Non-Human Primate and Human Studies." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/882.

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Many steps go into developing a clinical viral gene therapy. The course starts with appropriate disease selection and moves through the many hurdles of in-vitro testing, animal model validation and proof-of-concept studies, all the way through pre-clinical large animal studies. In this thesis, I propose to outline the process of developing a translation pathway for a gene therapy using recombinant adeno-associated virus (rAAV). I will expand on this outline using data that I have generated during the course of my Ph.D. that ranges from animal model validation all the way through pre-clinical vector stability studies. Two disease models will be discussed throughout this thesis, Cockayne Syndrome (CS) and Alpha-1 Antitrypsin Deficiency (AATD). Cockayne Syndrome is a rare autosomal recessive genetic disorder involving mutations in either the CSA or CSB gene, leading to defects in DNA repair. Clinically this presents as progressive degeneration of the central nervous system, retina, cardiovascular system, and cochlea, which leads to mental retardation, post-natal growth defects, ocular abnormalities, and shortened life expectancy. Alpha-1 antitrypsin is a serine protease inhibitor largely produced in the liver that mainly functions to inhibit neutrophil elastase within the lung. AATD leads to an increased risk of emphysema, with shortened life expectancy, and also results in accumulations of mutant AAT polymers in the liver, sometimes leading to liver failure. Using these two disease models I will outline the upstream and downstream pre-clinical work as well as the transition to clinical trials of a rAAV based gene therapy.
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49

Wang, Ke-Sheng, Liang Wang, Shimin Zheng, and Long-Yang Wu. "Associations of Smoking Status and Serious Psychological Distress with Chronic Obstructive Pulmonary Disease." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/39.

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Background: Chronic obstructive pulmonary disease (COPD) has been a major public health problem due to its high prevalence, morbidity, and mortality. Smoking is a major risk factor for COPD, while serious psychological distress (SPD) is prevalent among COPD patients. However, no study focusing on the effect of SPD on COPD has been so far conducted, while few studies have focused on the associations of SPD and behavioral factors with COPD by smoking status. Objectives: This study aimed to examine the associations of SPD and behavioral factors (such as smoking and physical activity) with COPD. Materials and Methods: Weighted logistic regression models were used for the analysis of 1,248 cases and 39,995 controls from the 2005 California Health Interview Survey (CHIS). Results: The prevalence of SPD was 10% in cases and 4% in controls, respectively. The percentages of past and current smoking were higher in cases than controls (50% vs. 24% and 27% vs. 15%, respectively). After adjusting for other factors, smoking (OR = 4.56, 95% CI = 3.41-6.11 and OR = 3.24, 95% CI = 2.57-4.08 for current and past smoking, respectively), physical activity (OR = 0.69, 95% CI = 0.55-0.87), obesity (OR = 1.25, 95% CI = 1.03-1.52), older age (OR = 2.86, 95% CI = 2.15-3.82, and OR = 5.97, 95% CI = 4.42-8.08 for middle-aged and elder groups, respectively), SPD (OR = 2.11, 95% CI = 1.47-3.04), employment (OR = 0.62, 95% CI = 0.51-0.76), race (OR = 0.35, 95% CI = 0.23-0.54, OR = 0.59, 95% CI = 0.36-0.97, and OR = 0.47, 95% CI=0.29-0.75 for Latino, Asian, and African American, respectively) and lower federal poverty level (OR=1.89, 95% CI = 1.35-2.63, OR = 1.65, 95% CI = 1.27-2.14, and OR = 1.39, 95% CI = 1.12-1.72 for 0-99% FPL, 100-199% FPL and 200-299% FPL, respectively) were all associated with COPD (P < 0.05). Age group, SPD, race, and employment showed significant interactions with smoking status. Stratified by smoking status, aging was the only risk factor for COPD in the never smoking group; whereas, lack of physical activity, older age, SPD, race, unemployment, and lower federal poverty level were associated with COPD in the smoking groups. Conclusions: Smoking and aging were major risk factors for COPD, while lack of physical activity and SPD were strongly associated with COPD in the smoking groups.
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50

Doke, Mayur Arvind. "The Role of ID3 and PCB153 in the Hyperproliferation and Dysregulation of Lung Endothelial Cells." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3808.

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Abstract:
Uncontrolled growth of vascular stem cells as a result of endothelial-mesenchymal transition is considered to cause hyper-proliferative vascular remodeling in severe pulmonary arterial hypertension (PAH) patients. Hyperplastic intimal growth is one of the causes of closure of the lumen of pulmonary arterioles. This abnormal vessel remodeling leads to the progressive increase in pressure of the pulmonary arterioles causing severe PAH; and debilitating harm to patients resulting in mortality from right heart failure. Environmental factors, including polychlorinated biphenyls (PCBs), are considered to be involved in hyper-proliferative vascular remodeling because genetic makeup can only explain about 10% of severe PAH cases. PCB involvement in lung toxicity has received attention because (i) they have been reported to accumulate in the lung; (ii) PCBs produce pathological vascular remodeling in the experimental model; high levels of PCBs are found in human lung tissue; and (iii) epidemiological studies show the association between lung toxicity and PCBs; and prevalence of hypertension and elevated concentrations of particularly PCB153. Recent studies identify PCB153 as one of the largest contributors for total PCB body burden in humans. Our previous studies demonstrated PCB153 mediated vascular endothelial dysfunction and activated the inhibitor of differentiation protein 3 (ID3). ID3 is an important determinant of mitogen and reactive oxygen species-induced G1→S phase cell cycle progression. Although phosphorylation of ID3 increases cell growth by antagonizing the transcription of cell cycle inhibitors, still there is a critical gap in understanding the molecular mechanism(s) of pulmonary proliferative vascular remodeling associated with PCB exposure in humans and the role of the transcription regulator ID3. Our overall objective was to investigate ID3 mediated transcriptional reprogramming as a driver of PCB153-induced pathological proliferative vascular remodeling. Stable ectopic expression of ID3 in lung endothelial cells contributed to endothelial-mesenchymal transition (EndMT), cell proliferation, and cell migration. Using an endothelial spheroid assay, an established method to measure aberrant hyper-proliferation of endothelial cells in PAH patients, we show that stable ectopic expression of ID3 increased the number and size of vascular spheres. ID3 overexpressing cells exposed to environmentally relevant concentrations of PCB153 showed a two-fold increase in cell proliferation as determined by MTT, SRB, and BrdU assays. ID3 overexpressing cells showed the loss of VE-cadherin and gain of MMP9 and vimentin, which are markers of EndMT. PCB153 also increased phosphorylation of ID3 in lung endothelial cells. To determine the molecular mechanism by which ID3 contributes to hyper-proliferative endothelial cells, we investigated ID3 transcriptional reprogramming using ChIP-Seq and RNA-Seq technology. We show here for the first time that ID3 is part of a more general mechanism of transcriptional regulation. Our ChIP-Seq data show that ID3 binds to a subset of approximately 1200 target genes. Comprehensive motif analysis of ChIP-Seq data using the MEME Suite software toolkit revealed that ID3 bound to the GAGAGAGAGA motif sequence on genomic DNA. We also show a significant preference of ID3 binding to motifs associated with transcription factors IRF1, BC11A, IRF4, PRDM1, FOXJ3, SMAD4, ZBTB6, GATA1, and STAT2. Using an integrative approach of ChIP-Seq and RNA-Seq data, we identified 19 genes whose promoter region was bound by ID3 and RNA was differentially expressed in ID3 overexpressing cells. In summary, our data demonstrated that PCB153 and/or ID3 induces proliferation of lung endothelial cells via transcriptional reprogramming. Discoveries from these findings will lay the necessary groundbreaking work for testing the efficacy of ID3 antagonists for the prevention and treatment of pathological vascular remodeling as well as provide a new paradigm by which PCBs may contribute to lung vascular toxicity.
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