Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

PubMed

Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

2012-04-15

Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herring, M.J.; Putney, L.F.; St George, J.A.

In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergenmore » (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)« less

Chlamydia vaccine candidates and tools for chlamydial antigen discovery.

PubMed

Rockey, Daniel D; Wang, Jie; Lei, Lei; Zhong, Guangming

2009-10-01

The failure of the inactivated Chlamydia-based vaccine trials in the 1960s has led researchers studying Chlamydia to take cautious and rational approaches to develop safe and effective chlamydial vaccines. Subsequent research efforts focused on three areas. The first is the analysis of the immunobiology of chlamydial infection in animal models, with supporting clinical studies, to identify the immune correlates of both protective immunity and pathological responses. Second, recent radical improvements in genomics, proteomics and associated technologies have assisted in the implementation of creative approaches to search for suitable vaccine candidates. Third, progress in the analysis of host response and adjuvanticity regulating both innate and adaptive immunity at the mucosal site of infection has led to progress in the design of optimal delivery and adjuvant systems for enhancing protective immunity. Considerable progress has been made in the first two areas but research efforts to better define the factors that regulate immunity at mucosal sites of infection and to develop strategies to boost protective immunity via immunomodulation, effective delivery systems and potent adjuvants, have remained elusive. In this article, we will summarize progress in these areas with a focus on chlamydial vaccine antigen discovery, and discuss future directions towards the development of a safe and effective chlamydial vaccine.

Gender-based screening for chlamydial infection and divergent infection trends in men and women.

PubMed

Rogers, Susan M; Turner, Charles F; Miller, William C; Erbelding, Emily; Eggleston, Elizabeth; Tan, Sylvia; Roman, Anthony; Hobbs, Marcia; Chromy, James; Muvva, Ravikiran; Ganapathi, Laxminarayana

2014-01-01

To assess the potential impact of chlamydial screening policy that recommends routine screening of women but not men. Population surveys of probability samples of Baltimore adults aged 18 to 35 years in 1997-1998 and 2006-2009 collected biospecimens to estimate trends in undiagnosed chlamydial infection. Survey estimates are compared to surveillance data on diagnosed chlamydial infections reported to the Health Department. Prevalence of undiagnosed chlamydial infection among men increased from 1.6% to 4.0%, but it declined from 4.3% to 3.1% among women (p = 0.028 for test of interaction). The annual (average) number of diagnosed infections was substantially higher among women than men in both time periods and increased among both men and women. Undiagnosed infection prevalence was substantially higher among black than non-black adults (4.0% vs 1.2%, p = 0.042 in 1997-98 and 5.5% vs 0.7%, p<0.001 in 2006-09). Divergent trends in undiagnosed chlamydial infection by gender parallel divergent screening recommendations that encourage chlamydial testing for women but not for men.

[Newer diagnostic procedures for chlamydial diseases (author's transl)].

PubMed

Edlinger, E; Ardoin, P

1981-12-01

Chlamydiales are bacteries showing a growth cycle unique among procaryotes. The two species Chlamydia trachomatis and Chlamydia psittaci are genetically very distant and their pathogenicity for man is very distinct. Human chlamydial infections by Chlamydia trachomatis are diseases chiefly sexually transmitted and their epidemiological importance is growing. The relationship between chlamydial infections, Reiter disease, and cat scratch disease are discussed. The various laboratory diagnostic procedures are reported, including the techniques and their indications; the method of choice is in the majority of cases the isolation of Chlamydia on cell culture.

Gender-Based Screening for Chlamydial Infection and Divergent Infection Trends in Men and Women

PubMed Central

Rogers, Susan M.; Turner, Charles F.; Miller, William C.; Erbelding, Emily; Eggleston, Elizabeth; Tan, Sylvia; Roman, Anthony; Hobbs, Marcia; Chromy, James; Muvva, Ravikiran; Ganapathi, Laxminarayana

2014-01-01

Objectives To assess the potential impact of chlamydial screening policy that recommends routine screening of women but not men. Methods Population surveys of probability samples of Baltimore adults aged 18 to 35 years in 1997–1998 and 2006–2009 collected biospecimens to estimate trends in undiagnosed chlamydial infection. Survey estimates are compared to surveillance data on diagnosed chlamydial infections reported to the Health Department. Results Prevalence of undiagnosed chlamydial infection among men increased from 1.6% to 4.0%, but it declined from 4.3% to 3.1% among women (p = 0.028 for test of interaction). The annual (average) number of diagnosed infections was substantially higher among women than men in both time periods and increased among both men and women. Undiagnosed infection prevalence was substantially higher among black than non-black adults (4.0% vs 1.2%, p = 0.042 in 1997–98 and 5.5% vs 0.7%, p<0.001 in 2006–09). Conclusion Divergent trends in undiagnosed chlamydial infection by gender parallel divergent screening recommendations that encourage chlamydial testing for women but not for men. PMID:24586491

Chlamydial and Rickettsial Infections

DTIC Science & Technology

1989-01-01

distributed in nature, and causes acute disease and persistent infections in a variety of vertebrate and invertebrate hosts. Transmission of C. psittaci may...specific and acquired immunity in the control of diseases caused by the chlamydiae has been demonstrated, it is important to recognise that immunity...means clear, but certain changes that accompany resolution of acute chlamydial disease may contribute to persistent or chronic infections. Indeed

Innate Immunity to Respiratory Infection in Early Life

PubMed Central

Lambert, Laura; Culley, Fiona J.

2017-01-01

Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung. PMID:29184555

Effects of intratracheal budesonide during early postnatal life on lung maturity of premature fetal rabbits.

PubMed

Li, Ling; Yang, Chen; Feng, Xiuliang; Du, Yongping; Zhang, Zhihong; Zhang, Yueping

2018-01-01

This study aimed to study the effects of intratracheal instillation of budesonide on lung maturity of premature fetal rabbits. The developmental pattern of pulmonary alveoli in rabbits is similar to that in humans. Fetal rabbits were taken out from female rabbits on the 28th day of pregnancy (full term = 31 days) by cesarean section (c-section). The fetal rabbits were divided into four groups: control (normal saline, NS), budesonide (budesonide, BUD), calf pulmonary surfactant for injection (pulmonary surfactant, PS), and calf pulmonary surfactant + budesonide for injection (pulmonary surfactant + budesonide, PS + BUD). All premature rabbits were kept warm after c-section. After 15-min autonomous respiration, a tracheal cannula was implemented for instilling NS, BUD, PS, and PS + BUD. The morphology of lung tissues of premature fetal rabbits was analyzed using optical and electron microscopes. Surfactant protein B (SP-B) mRNA and protein levels in lung tissues were determined using polymerase chain reaction and Western blotting, respectively. Intratracheal instillation of BUD could increase the alveolar area of the fetal rabbits (P < 0.01), decrease the alveolar wall thickness (P < 0.01), and increase the mean density of lamellar bodies (P < 0.05) and SP-B protein levels in type II epithelial cells of pulmonary alveoli (P < 0.05). Intratracheal instillation of BUD during early postnatal life is effective in promoting alveolarization and increasing SP-B expression, the pro-pulmonary maturity of BUD combined with PS is superior to that of BUD or PS alone. However, the long-term effect of BUD on lung development needs further exploration. © 2017 Wiley Periodicals, Inc.

Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression

PubMed Central

Saravia, Jordy; You, Dahui; Thevenot, Paul; Lee, Greg I.; Shrestha, Bishwas; Lomnicki, Slawo; Cormier, Stephania A.

2013-01-01

Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-life CDPM exposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPM+HDM failed to develop a typical asthma phenotype including airway hyperresponsiveness, Th2-inflammation, Muc5ac expression, eosinophilia, and HDM-specific Ig compared to HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was two-fold higher in CDPM+HDM mice compared to HDM-mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and Tregs, resulting in suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific-antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life. PMID:24172848

Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

PubMed Central

Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

2016-01-01

Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

Early Lung Cancer Diagnosis by Biosensors

PubMed Central

Zhang, Yuqian; Yang, Dongliang; Weng, Lixing; Wang, Lianhui

2013-01-01

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. PMID:23892596

A population-based prospective cohort study examining the influence of early-life respiratory tract infections on school-age lung function and asthma.

PubMed

van Meel, Evelien R; den Dekker, Herman T; Elbert, Niels J; Jansen, Pauline W; Moll, Henriëtte A; Reiss, Irwin K; de Jongste, Johan C; Jaddoe, Vincent W V; Duijts, Liesbeth

2018-02-01

Early-life respiratory tract infections could affect airway obstruction and increase asthma risk in later life. However, results from previous studies are inconsistent. We examined the associations of early-life respiratory tract infections with lung function and asthma in school-aged children. This study among 5197 children born between April 2002 and January 2006 was embedded in a population-based prospective cohort study. Information on physician-attended upper and lower respiratory tract infections until age 6 years (categorised into ≤ 3 and >3-6 years) was obtained by annual questionnaires. Spirometry measures and physician-diagnosed asthma were assessed at age 10 years. Upper respiratory tract infections were not associated with adverse respiratory outcomes. Compared with children without lower respiratory tract infections ≤3 years, children with lower respiratory tract infections ≤3 years had a lower FEV 1 , FVC, FEV 1 :FVC and forced expiratory flow at 75% of FVC (FEF 75 ) (Z-score (95% CI): ranging from -0.22 (-0.31 to -0.12) to -0.12 (-0.21 to -0.03)) and an increased risk of asthma (OR (95% CI): 1.79 (1.19 to 2.59)). Children with lower respiratory tract infections >3-6 years had an increased risk of asthma (3.53 (2.37 to 5.17)) only. Results were not mediated by antibiotic or paracetamol use and not modified by inhalant allergic sensitisation. Cross-lagged modelling showed that results were not bidirectional and independent of preschool wheezing patterns. Early-life lower respiratory tract infections ≤3 years are most consistently associated with lower lung function and increased risk of asthma in school-aged children. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Determinants of Quality of Life in Lung Cancer Patients.

PubMed

Hung, Hsiu-Yu; Wu, Li-Min; Chen, Kang-Pan

2018-05-01

To examine the relationships of self-care, symptoms, and a variety of demographic factors to quality of life (QOL), and to identify determinants of QOL in lung cancer patients undergoing chemotherapy. A cross-sectional, correlational study. 159 patients with lung cancer undergoing chemotherapy were recruited from three southern hospitals in Taiwan. Four instruments were used: the Quality of Life Questionnaire Core 30-item (QLQ-C30), M.D. Anderson Symptom Inventory (MDASI), Memorial Symptom Assessment Scale-Short Form (MSAS-SF), and Self-Care Behavior Scale (SCBS). Lung cancer patients rated lower scores of self-care behaviors on food choice and nutrition maintenance, regular exercise and sleep, and medical compliance. Being younger, having spouses as main caregivers, having food choice and nutrition maintenance, and getting regular exercise and sleep were associated with better QOL. Degree of interference with life, age, food choice and nutrition maintenance, and psychological symptoms were found to predict functional QOL and accounted for 43% of total variance. The findings identified factors influencing QOL and provided evidence for designing an intervention to enhance QOL in lung cancer patients undergoing chemotherapy. The findings may be useful for guiding intervention development for early detection and management of symptom interference with daily living, and place greater focus on patient self-care to promote food choice and nutrition maintenance, especially in older patients and those whose caregivers are not their spouses. © 2018 Sigma Theta Tau International.

Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life® in pig lung transplantation model.

PubMed

Glorion, M; Polard, V; Favereau, F; Hauet, T; Zal, F; Fadel, E; Sage, E

2017-10-25

We describe the results of adding a new biological agent HEMO 2 life ® to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMO 2 life ® is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex ® ) was compared with Perfadex ® associated with HEMO 2 life ® and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMO 2 life ® group led to significant improvement in functional parameters: reduction of graft vascular resistance (p < .05) and increase in graft oxygenation ratio (p < .05). Several ischemia-reperfusion related biomarkers showed positive trends in the HEMO 2 life ® group: expression of HMG B1 in serum tended to be lower in comparison (2.1 ± 0.8 vs. 4.6 ± 1.5) with Perfadex ® group, TNF-α and IL-8 in BALF were significantly higher in the two experimental groups compared to control (p < .05). During cold ischemia, expression of HIF1α and histology remained unchanged and similar to control. Supplementation of the Perfadex ® solution by an innovative oxygen carrier HEMO 2 life ® during hypothermic static preservation improves early graft function after prolonged cold ischemia in lung transplantation.

African ancestry, early life exposures, and respiratory morbidity in early childhood.

PubMed

Kumar, R; Tsai, H-J; Hong, X; Gignoux, C; Pearson, C; Ortiz, K; Fu, M; Pongracic, J A; Burchard, E G; Bauchner, H; Wang, X

2012-02-01

Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and

African ancestry, early life exposures, and respiratory morbidity in early childhood

PubMed Central

Kumar, R.; Tsai, H.-J.; Hong, X.; Gignoux, C.; Pearson, C.; Ortiz, K.; Fu, M.; Pongracic, J. A.; Burchard, E. G.; Bauchner, H.; Wang, X.

2012-01-01

Summary Background Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. Objective To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. Methods We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Results Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. Conclusions and Clinical Relevance In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to

Liquid biopsy for early detection of lung cancer.

PubMed

Hofman, Paul

2017-01-01

The possibility of complete recovery for a lung cancer patient depends on very early diagnosis, as it allows total surgical resection. Screening for this cancer in a high-risk population can be performed using a radiological approach, but this holds a certain number of limitations. Liquid biopsy could become an alternative and complementary screening approach to chest imaging for early diagnosis of lung cancer. Several circulating biomarkers indicative of lung cancer can be investigated in blood, such as circulating tumor cells, circulating free nucleic acids (RNA and DNA) and proteins. However, none of these biomarkers have yet been adopted in routine clinical practice and studies are ongoing to confirm or not the usefulness and practical interest in routine early diagnosis and screening for lung cancers. Several potential circulating biomarkers for the early detection of lung cancer exist. When coupled to thoracic imaging, these biomarkers must give diagnosis of a totally resectable lung cancer and potentially provide new recommendations for surveillance by imagery of high-risk populations without a detectable nodule. Optimization of the specificity and sensitivity of the detection methods as well as standardization of the techniques is essential before considering for daily practice a liquid biopsy as an early diagnostic tool, or possibly as a predictive test, of lung cancer.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile.

PubMed

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-12-15

Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60μg/L; and Arica, with long-term water concentrations ≤10μg/L. Compared to adults never exposed >10μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath=5.56, 90% confidence interval (CI): 2.68-11.5), and decreases in pulmonary function (e.g., 224mL decrease in forced vital capacity in nonsmokers, 90% CI: 97-351mL). Subjects with long-term exposure to arsenic water concentrations near 60μg/L also had increases in some pulmonary symptoms and reduced lung function. Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. Copyright © 2016 Elsevier Inc. All rights reserved.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

PubMed Central

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-01-01

Background Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958–1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤10 μg/L. Results Compared to adults never exposed >10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 ml decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 ml). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. PMID:27725189

Crossing the border - Solute entry into the chlamydial inclusion.

PubMed

Haferkamp, Ilka

2017-08-26

Chlamydiales comprise important human and animal pathogens as well as endosymbionts of amoebae. Generally, these obligate intracellular living bacteria are characterized by a biphasic developmental cycle, a reduced genome and a restricted metabolic capacity. Because of their metabolic impairment, Chlamydiales essentially rely on the uptake of diverse metabolites from their hosts. Chlamydiales thrive in a special compartment, the inclusion, and hence are surrounded by an additional membrane. Solutes might enter the inclusion through pores and open channels or by redirection of host vesicles, which fuse with the inclusion membrane and release their internal cargo. Recent investigations shed new light on the chlamydia-host interaction and identified an additional way for nutrient uptake into the inclusion. Proteome studies and targeting analyses identified chlamydial and host solute carriers in inclusions of Chlamydia trachomatis infected cells. These transporters are involved in the provision of UDP-glucose and biotin, and probably deliver further metabolites to the inclusion. By the controlled recruitment of specific solute carriers to the inclusion, the chlamydial resident thus can actively manipulate the metabolite availability and composition in the inclusion. This review summarizes recent findings and new ideas on carrier mediated solute uptake into the chlamydial inclusion in the context of the bacterial and host metabolism. Copyright © 2017 Elsevier GmbH. All rights reserved.

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

PubMed

Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

2015-01-01

Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evolution of cystic fibrosis lung function in the early years.

PubMed

Bush, Andrew; Sly, Peter D

2015-11-01

Most treatment of newborn screening-diagnosed cystic fibrosis is not evidence-based; there are very few randomized controlled trials (RCTs). Furthermore, the advent of novel molecular therapies, which could be started at diagnosis, mandates performing RCTs in very young children. However, unless the natural history of early cystic fibrosis lung disease is known, RCTs are impossible. Here, we review the results of two large prospective cohorts of these infants - London Cystic Fibrosis Collaboration (LCFC) (London, UK) and Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF) (Australia). Nutritional status remained excellent in both the cohorts. Both cohorts reported abnormal lung function aged at 3 months. AREST-CF, which previously reported rapidly declining preschool lung function, now report good conventional school-age spirometry. LCFC reported improvement between 3 months and 1 year, and stability in the second year. AREST-CF also reported a high prevalence of high resolution computed tomographic abnormalities related to free neutrophil elastase in bronchoalveolar lavage; LCFC reported high resolution computed tomographic changes at 1 year, which were too mild to be scored reproducibly. At least in the first 2 years of life, lung function is not a good end-point for RCTs; routine bronchoalveolar lavage and HRCT cannot be justified. Newborn screening has greatly improved outcomes, but we need better point-of-care biomarkers.

The Chlamydia-Secreted Protease CPAF Promotes Chlamydial Survival in the Mouse Lower Genital Tract

PubMed Central

Yang, Zhangsheng; Tang, Lingli; Shao, Lili; Zhang, Yuyang; Zhang, Tianyuan; Schenken, Robert; Valdivia, Raphael

2016-01-01

Despite the extensive in vitro characterization of CPAF (chlamydial protease/proteasome-like activity factor), its role in chlamydial infection and pathogenesis remains unclear. We now report that a Chlamydia trachomatis strain deficient in expression of CPAF (L2-17) is no longer able to establish a successful infection in the mouse lower genital tract following an intravaginal inoculation. The L2-17 organisms were cleared from the mouse lower genital tract within a few days, while a CPAF-sufficient C. trachomatis strain (L2-5) survived in the lower genital tract for more than 3 weeks. However, both the L2-17 and L2-5 organisms maintained robust infection courses that lasted up to 4 weeks when they were directly delivered into the mouse upper genital tract. The CPAF-dependent chlamydial survival in the lower genital tract was confirmed in multiple strains of mice. Thus, we have demonstrated a critical role of CPAF in promoting C. trachomatis survival in the mouse lower genital tracts. It will be interesting to further investigate the mechanisms of the CPAF-dependent chlamydial pathogenicity. PMID:27382018

Antigenic topology of chlamydial PorB protein and identification of targets for immune neutralization of infectivity.

PubMed

Kawa, Diane E; Stephens, Richard S

2002-05-15

The outer membrane protein PorB is a conserved chlamydial protein that functions as a porin and is capable of eliciting neutralizing Abs. A topological antigenic map was developed using overlapping synthetic peptides representing the Chlamydia trachomatis PorB sequence and polyclonal immune sera. To identify which antigenic determinants were surface accessible, monospecific antisera were raised to the PorB peptides and were used in dot-blot and ELISA-based absorption studies with viable chlamydial elementary bodies (EBs). The ability of the surface-accessible antigenic determinants to direct neutralizing Ab responses was investigated using standardized in vitro neutralization assays. Four major antigenic clusters corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2-4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were identified. Collectively, the EB absorption and dot-blot assays established that the immunoreactive PorB Ags were exposed on the surface of chlamydial EBs. Peptide-specific antisera raised to the surface-accessible Ags neutralized chlamydial infectivity and demonstrated cross-reactivity to synthetic peptides representing analogous C. pneumoniae PorB sequences. Furthermore, neutralization of chlamydial infectivity by C. trachomatis PorB antisera was inhibited by synthetic peptides representing the surface-exposed PorB antigenic determinants. These findings demonstrate that PorB Ags may be useful for development of chlamydial vaccines.

Biochemical characterisation of the chlamydial MurF ligase, and possible sequence of the chlamydial peptidoglycan pentapeptide stem.

PubMed

Patin, Delphine; Bostock, Julieanne; Chopra, Ian; Mengin-Lecreulx, Dominique; Blanot, Didier

2012-06-01

Chlamydiaceae are obligate intracellular bacteria that do not synthesise detectable peptidoglycan although they possess an almost complete arsenal of genes encoding peptidoglycan biosynthetic activities. In this paper, the murF gene from Chlamydia trachomatis was shown to be capable of complementing a conditional Escherichia coli mutant impaired in UDP-MurNAc-tripeptide:D-Ala-D-Ala ligase activity. Recombinant MurF from C. trachomatis was overproduced and purified from E. coli. It exhibited ATP-dependent UDP-MurNAc-X-γ-D-Glu-meso-A(2)pm:D-Ala-D-Ala ligase activity in vitro. No significant difference of kinetic parameters was seen when X was L-Ala, L-Ser or Gly. The L-Lys-containing UDP-MurNAc-tripeptide was a poorer substrate as compared to the meso-A(2)pm-containing one. Based on the respective substrate specificities of the chlamydial MurC, MurE, MurF and Ddl enzymes, a sequence L-Ala/L-Ser/Gly-γ-D-Glu-meso-A(2)pm-D-Ala-D-Ala is expected for the chlamydial pentapeptide stem, with Gly at position 1 being less likely.

Life after a lung transplant: a balance of joy and challenges.

PubMed

Graarup, Jytte; Mogensen, Elin Lindberg; Missel, Malene; Berg, Selina Kikkenborg

2017-11-01

To describe patients' experiences throughout the first four months post-lung transplant. Health professionals are familiar with the fact that patients' average survival after a lung transplant is about seven years and that 74% of these patients reject new organs within the first two years. By contrast, knowledge of these patients' perspectives after lung transplantation is scant. A qualitative study was conducted between May 2013-May 2014 in which 26 interviewees participated - four months post-transplant - based on a semistructured interview guide. The data were inductively analysed using a content thematic approach within a phenomenological and hermeneutic frame. The main findings in the study reveal that (1) having a lung transplant is an overwhelming experience, which for some patients includes (2) troubling physical and psychological challenges. The interviewees were happy to get another chance to live, although some of them suffered from medical side effects, postoperative complications and psychological problems. When asked about the future, interviewees stated that life could be described as (3) a balance of joy and challenges. They had received a new chance in life and were eager to fulfil their life hopes and dreams. At the same time, they were worried about the future. Having a lung transplant implies rules that have to be followed. What are the healthy choices they are supposed to make? And will there be a tomorrow? Having a lung transplant is described as an overwhelming experience because of the improvement in the physical function of the body. Patients were grateful to family, friends and healthcare professionals for supporting them. The first four months post-transplantation were described as both physically and psychologically challenging. Interviewees were aware of the prognosis for patients following lung transplantation. They expressed feelings of worry and insecurity but still had hopes and dreams. The patients are troubled by both physical and

Intensity of Anxiety and Depression in Patients with Lung Cancer in Relation to Quality of Life.

PubMed

Polański, Jacek; Chabowski, Mariusz; Chudiak, Anna; Uchmanowicz, Bartosz; Janczak, Dariusz; Rosińczuk, Joanna; Mazur, Grzegorz

2018-01-01

Psychological factors, such as the anxiety and depression, which often occur in patients with lung cancer might negatively influence their quality of life. The aim of the study was to evaluate the effect of anxiety and depression in lung cancer patients on quality of life. The study included 180 lung patients of the mean age of 62.7 ± 9.7 years. The following scales were employed in the study: Quality of Life Questionnaire QLQ-C30 and LC13 scale, and Hospital Anxiety and Depression scale (HADS). The overall score of quality of life measured by QLQ-C30 was 47.1 ± 23.4 points on a hundred-point scale. Anxiety was diagnosed in 67 patients (37.2%) and depression in 75 patients (41.7%) by HADS. Quality of life was significantly worse in case of anxiety and depression (p < 0.05), which negatively influenced both functional and symptom intensity scales measured with QLQ-C30 and QLQ-LC13. We conclude that early identification of anxiety and depression may help in therapeutic decision-making and may be a useful predictive factor in lung cancer patients.

Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

PubMed

Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

2014-07-01

Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Chlamydia-Secreted Protease CPAF Promotes Chlamydial Survival in the Mouse Lower Genital Tract.

PubMed

Yang, Zhangsheng; Tang, Lingli; Shao, Lili; Zhang, Yuyang; Zhang, Tianyuan; Schenken, Robert; Valdivia, Raphael; Zhong, Guangming

2016-09-01

Despite the extensive in vitro characterization of CPAF (chlamydial protease/proteasome-like activity factor), its role in chlamydial infection and pathogenesis remains unclear. We now report that a Chlamydia trachomatis strain deficient in expression of CPAF (L2-17) is no longer able to establish a successful infection in the mouse lower genital tract following an intravaginal inoculation. The L2-17 organisms were cleared from the mouse lower genital tract within a few days, while a CPAF-sufficient C. trachomatis strain (L2-5) survived in the lower genital tract for more than 3 weeks. However, both the L2-17 and L2-5 organisms maintained robust infection courses that lasted up to 4 weeks when they were directly delivered into the mouse upper genital tract. The CPAF-dependent chlamydial survival in the lower genital tract was confirmed in multiple strains of mice. Thus, we have demonstrated a critical role of CPAF in promoting C. trachomatis survival in the mouse lower genital tracts. It will be interesting to further investigate the mechanisms of the CPAF-dependent chlamydial pathogenicity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Use of a Guinea Pig-Specific Transcriptome Array for Evaluation of Protective Immunity against Genital Chlamydial Infection following Intranasal Vaccination in Guinea Pigs

PubMed Central

Veselenak, Ronald L.; Li, Yansong; Yu, Jieh-Juen; Murthy, Ashlesh K.; Cap, Andrew P.; Guentzel, M. Neal; Chambers, James P.; Zhong, Guangming; Rank, Roger G.; Pyles, Richard B.; Arulanandam, Bernard P.

2014-01-01

Guinea pigs have been used as a second animal model to validate putative anti-chlamydial vaccine candidates tested in mice. However, the lack of guinea pig-specific reagents has limited the utility of this animal model in Chlamydia sp. vaccine studies. Using a novel guinea pig-specific transcriptome array, we determined correlates of protection in guinea pigs vaccinated with Chlamydia caviae (C. caviae) via the intranasal route, previously reported by us and others to provide robust antigen specific immunity against subsequent intravaginal challenge. C. caviae vaccinated guinea pigs resolved genital infection by day 3 post challenge. In contrast, mock vaccinated animals continued to shed viable Chlamydia up to day 18 post challenge. Importantly, at day 80 post challenge, vaccinated guinea pigs experienced significantly reduced genital pathology - a sequelae of genital chlamydial infections, in comparison to mock vaccinated guinea pigs. Sera from vaccinated guinea pigs displayed antigen specific IgG responses and increased IgG1 and IgG2 titers capable of neutralizing GPIC in vitro. Th1-cellular/inflammatory immune genes and Th2-humoral associated genes were also found to be elevated in vaccinated guinea pigs at day 3 post-challenge and correlated with early clearance of the bacterium. Overall, this study provides the first evidence of guinea pig-specific genes involved in anti-chlamydial vaccination and illustrates the enhancement of the utility of this animal model in chlamydial pathogenesis. PMID:25502875

Copper(II)-bis(thiosemicarbazonato) complexes as anti-chlamydial agents.

PubMed

Marsh, James W; Djoko, Karrera Y; McEwan, Alastair G; Huston, Wilhelmina M

2017-09-29

Lipophilic copper (Cu)-containing complexes have shown promising antibacterial activity against a range of bacterial pathogens. To examine the susceptibility of the intracellular human pathogen Chlamydia trachomatis to copper complexes containing bis(thiosemicarbazone) ligands [Cu(btsc)], we tested the in vitro effect of CuII-diacetyl- and CuII-glyoxal-bis[N(4)-methylthiosemicarbazonato] (Cu(atsm) and Cu(gtsm), respectively) on C. trachomatis. Cu(atsm) and to a greater extent, Cu(gtsm), prevented the formation of infectious chlamydial progeny. Impacts on host cell viability and respiration were also observed in addition to the Chlamydia impacts. This work suggests that copper-based complexes may represent a new lead approach for future development of new therapeutics against chlamydial infections, although host cell impacts need to be fully explored. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Liquid biopsy for early stage lung cancer.

PubMed

Liang, Wenhua; Zhao, Yi; Huang, Weizhe; Liang, Hengrui; Zeng, Haikang; He, Jianxing

2018-04-01

Liquid biopsy, which analyzes biological fluids especially blood specimen to detect and quantify circulating cancer biomarkers, have been rapidly introduced and represents a promising potency in clinical practice of lung cancer diagnosis and prognosis. Unlike conventional tissue biopsy, liquid biopsy is non-invasive, safe, simple in procedure, and is not influenced by manipulators' skills. Notably, some circulating cancer biomarkers are already detectable in disease with low-burden, making liquid biopsy feasible in detecting early stage lung cancer. In this review, we described a landscape of different liquid biopsy methods by highlighting the rationale and advantages, accessing the value of various circulating biomarkers and discussing their possible future development in the detection of early lung cancer.

Targeting eukaryotic Rab proteins: a smart strategy for chlamydial survival and replication.

PubMed

Damiani, María Teresa; Gambarte Tudela, Julián; Capmany, Anahí

2014-09-01

Chlamydia, an obligate intracellular bacterium which passes its entire lifecycle within a membrane-bound vacuole called the inclusion, has evolved a variety of unique strategies to establish an advantageous intracellular niche for survival. This review highlights the mechanisms by which Chlamydia subverts vesicular transport in host cells, particularly by hijacking the master controllers of eukaryotic trafficking, the Rab proteins. A subset of Rabs and Rab interacting proteins that control the recycling pathway or the biosynthetic route are selectively recruited to the chlamydial inclusion membrane. By interfering with Rab-controlled transport steps, this intracellular pathogen not only prevents its own degradation in the phagocytic pathway, but also creates a favourable intracellular environment for growth and replication. Chlamydia, a highly adapted and successful intracellular pathogen, has several redundant strategies to re-direct vesicles emerging from biosynthetic compartments that carry host molecules essential for bacterial development. Although current knowledge is limited, the latest findings have shed light on the role of Rab proteins in the course of chlamydial infections and could open novel opportunities for anti-chlamydial therapy. © 2014 John Wiley & Sons Ltd.

Screening and syndromic approaches to identify gonorrhea and chlamydial infection among women.

PubMed

Sloan, N L; Winikoff, B; Haberland, N; Coggins, C; Elias, C

2000-03-01

The standard diagnostic tools to identify sexually transmitted infections are often expensive and have laboratory and infrastructure requirements that make them unavailable to family planning and primary health-care clinics in developing countries. Therefore, inexpensive, accessible tools that rely on symptoms, signs, and/or risk factors have been developed to identify and treat reproductive tract infections without the need for laboratory diagnostics. Studies were reviewed that used standard diagnostic tests to identify gonorrhea and cervical chlamydial infection among women and that provided adequate information about the usefulness of the tools for screening. Aggregation of the studies' results suggest that risk factors, algorithms, and risk scoring for syndromic management are poor indicators of gonorrhea and chlamydial infection in samples of both low and high prevalence and, consequently, are not effective mechanisms with which to identify or manage these conditions. The development and evaluation of other approaches to identify gonorrhea and chlamydial infections, including inexpensive and simple laboratory screening tools, periodic universal treatment, and other alternatives must be given priority.

9 CFR 113.43 - Detection of chlamydial agents.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Detection of chlamydial agents. 113.43 Section 113.43 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... in a filed Outline of Production. (a) The yolk sac of 6-day-old chicken embryos shall be injected...

Patients' experiences of everyday life after lung transplantation.

PubMed

Thomsen, Doris; Jensen, Birte Østergaard

2009-12-01

To investigate the experiences of everyday life after lung transplantation of patients with previous chronic obstructive pulmonary disease (COPD). Compared with patients being transplanted due to other indications, those with COPD prior to lung transplantation report more problems in the form of shortness of breath, fatigue, sexual problems, insomnia and increased appetite. In addition, they are often faced with problems returning to normal working life. How these problems influence the patient's everyday life is unknown. An exploratory qualitative study. Ten COPD patients (five females and five males) aged 51-69 and more than six months post transplantation, were interviewed using of a semi-structured interview guide. All interviews were taperecorded, transcribed verbatim and analysed using qualitative content analysis. The analysis revealed four themes of experience: a second chance; an ordinary life without chronic rejection; even minor daily activities take time with chronic rejection; and need for support and knowledge that were considered important by the participants for their situation and daily life. This is the first study describing the experiences of everyday life after lung transplantation of patients with COPD prior to surgery. The findings highlight the importance of addressing these patients' experiences of gratitude, positive life orientation and informational needs in relation to everyday life. Health professionals should be aware of the kind of problems both women and men may experience a long time after the lung transplantation. They constitute a basic knowledge of a patient's everyday life that is important when planning individual counselling and rehabilitation.

Chlamydia trachomatis-host cell interactions: role of the chlamydial major outer membrane protein as an adhesin.

PubMed Central

Su, H; Watkins, N G; Zhang, Y X; Caldwell, H D

1990-01-01

The major outer membrane protein (MOMP) of Chlamydia trachomatis is characterized by four symmetrically spaced variable domains (VDs I to IV) whose sequences vary among serotypes. The surface-exposed portions of these VDs contain contiguous sequences that are both serotyping determinants and in vivo target sites for neutralizing antibodies. Previous studies using surface proteolysis of C. trachomatis B implicated VDs II and IV of the MOMP of this serotype in the attachment of chlamydiae to host cells. In this study, we used monoclonal antibodies (MAbs) specific to antigenic determinants located in VDs II and IV of the MOMP of serotype B to further investigate the role of the MOMP in the attachment of chlamydiae to host cells. MABs specific to serotype- and subspecies-specific epitopes located in exposed VDs II and IV, respectively, neutralized chlamydial infectivity for hamster kidney cells by blocking chlamydial attachment. We radioiodinated these MAbs and used them to determine the number and topology of the surface-exposed VDs II and IV epitopes on chlamydial elementary bodies. VDs II and IV each comprised approximately 2.86 x 10(4) negatively charged sites and were in proximity on the chlamydial cell surface. These studies suggest that the MAbs blocked chlamydial attachment by inhibiting electrostatic interactions with host cells. We examined the effects of thermal inactivation on both chlamydial attachment and conformation of the MOMP. Heat-inactivated chlamydiae failed to attach to host cells and exhibited a conformational change in an inaccessible invariant hydrophobic nonapeptide sequence located within VD IV of the MOMPs of C. trachomatis serotypes. These findings suggest that in addition to electrostatic interactions, a common hydrophobic component of the MOMP also contributes to the binding of chlamydiae to host cells. Thus, we propose that the MOMP functions as a chlamydial adhesin by promoting nonspecific (electrostatic and hydrophobic) interactions

Physical activity levels early after lung transplantation.

PubMed

Wickerson, Lisa; Mathur, Sunita; Singer, Lianne G; Brooks, Dina

2015-04-01

Little is known of the early changes in physical activity after lung transplantation. The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population. This was a prospective cohort study. Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire). Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=-.48, P=.007), daily steps (r=-.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=-.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps. Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study. Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise

Epidemiology of chlamydial infection and disease in a free-ranging koala (Phascolarctos cinereus) population

PubMed Central

Waugh, Courtney A.; Dong, Jianbao; Quigley, Bonnie L.; Hanger, Jonathan; Loader, Joanne; Polkinghorne, Adam; Timms, Peter

2017-01-01

Chlamydial disease continues to be one of the main factors threatening the long-term survival of the koala (Phascolarctos cinereus). Despite this, large epidemiological studies of chlamydial infection and disease in wild koala populations are lacking. A better understanding of the prevalence, transmission and pathogenesis is needed to improve control measures, such as the development of vaccines. We investigated the prevalence of Chlamydia pecorum infection and disease in 160 koalas in a peri-urban wild population in Queensland, Australia and found that 31% of koalas were Chlamydia PCR positive and 28% had clinically detectable chlamydial disease. Most infections were at the urogenital site (27%; both males and females) with only 14% at the ocular site. Interestingly, we found that 27% (4/15) of koalas considered to be sexually immature (9–13 months) were already infected with C. pecorum, suggesting that a significant percentage of animals are infected directly from their mother. Ocular infection levels were less prevalent with increasing age (8% in koalas older than 4 years), whereas the prevalence of urogenital tract infections remained high into older age (26% in koalas older than 4 years), suggesting that, after mother-to-young transmission, C. pecorum is predominantly a sexually transmitted infection. While 28% of koalas in this population had clinically detectable chlamydial disease (primarily urogenital tract disease), many PCR positive koalas had no detectable disease and importantly, not all diseased animals were PCR positive. We also observed higher chlamydial loads in koalas who were C. pecorum infected without clinical disease than in koalas who were C. pecorum infected with clinical disease. These results shed light on the potential mechanisms of transmission of C. pecorum in koalas and also guide future control measures, such as vaccination. PMID:29281731

Pre- and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life.

PubMed

de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais

2018-06-04

Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.

Strategic targeting of essential host-pathogen interactions in chlamydial disease.

PubMed

Coombes, B K; Johnson, D L; Mahony, J B

2002-09-01

The chlamydiae are obligate intracellular gram-negative bacteria that are exquisitely adapted for exploitation of their hosts and contribute to a wide range of acute and chronic human diseases. Acute infections treated with non-cidal antibiotics can lead to the development of persistent, non-replicating bacteria with the corollary that these persistent (yet viable) chlamydiae can resist eradication by further antimicrobial treatment and cause chronic disease. These findings highlight an urgent need for therapeutics that are effective against persistent infections and call for creative approaches to identify potential drug targets. The C. pneumoniae and C. trachomatis genome projects have greatly expanded our knowledge of chlamydial pathogenesis and have provided an enormous potential for the identification and characterization of unknown genes and potential virulence factors in these bacteria. As intracellular pathogens, chlamydiae rely on host cells for all aspects of their survival, from the initial attachment with host cell membranes, to cellular invasion, acquisition of host cell metabolites and intracellular replication. As such, the molecules participating in interactions with the host could be attractive targets for therapeutic intervention. This review describes recent advances in chlamydial genomics, proteomics and cell biology that have cast light on host-pathogen relations that are essential for chlamydial survival. Using this knowledge, we discuss how strategically interfering with essential interactions between chlamydiae and the host cell could be exploited to develop an innovative, and potentially more relevant arsenal of therapeutic compounds.

Early Life Wildfire Smoke Exposure Is Associated with Immune Dysregulation and Lung Function Decrements in Adolescence.

PubMed

Black, Carolyn; Gerriets, Joan E; Fontaine, Justin H; Harper, Richart W; Kenyon, Nicholas J; Tablin, Fern; Schelegle, Edward S; Miller, Lisa A

2017-05-01

The long-term health effects of wildfire smoke exposure in pediatric populations are not known. The objectives of this study were to determine if early life exposure to wildfire smoke can affect parameters of immunity and airway physiology that are detectable with maturity. We studied a mixed-sex cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008. Peripheral blood mononuclear cells (PBMCs) and pulmonary function measures were obtained when animals were approximately 3 years of age. PBMCs were cultured with either LPS or flagellin, followed by measurement of secreted IL-8 and IL-6 protein. PBMCs from a subset of female animals were also evaluated by Toll-like receptor (TLR) pathway mRNA analysis. Induction of IL-8 protein synthesis with either LPS or flagellin was significantly reduced in PBMC cultures from wildfire smoke-exposed female monkeys. In contrast, LPS- or flagellin-induced IL-6 protein synthesis was significantly reduced in PBMC cultures from wildfire smoke-exposed male monkeys. Baseline and TLR ligand-induced expression of the transcription factor, RelB, was globally modulated in PBMCs from wildfire smoke-exposed monkeys, with additional TLR pathway genes affected in a ligand-dependent manner. Wildfire smoke-exposed monkeys displayed significantly reduced inspiratory capacity, residual volume, vital capacity, functional residual capacity, and total lung capacity per unit of body weight relative to control animals. Our findings suggest that ambient wildfire smoke exposure during infancy results in sex-dependent attenuation of systemic TLR responses and reduced lung volume in adolescence.

Regional Emphysema Score Predicting Overall Survival, Quality of Life and Pulmonary Function Recovery in Early-stage Lung Cancer Patients

PubMed Central

Dai, Jie; Liu, Ming; Swensen, Stephen J.; Stoddard, Shawn M.; Wampfler, Jason A.; Limper, Andrew H.; Jiang, Gening; Yang, Ping

2017-01-01

Introduction Pulmonary emphysema is a common comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on patient’s overall survival, quality of life (QOL), and pulmonary function recovery in stage I–II lung cancer. Methods Between 1997 and 2009, 1,073 patients were identified and divided into two surgical groups (cancer in emphysematous [group 1, n=565] and non-emphysematous [group 2, n=435] region) and one non-surgical group (group 3, n=73). RES was derived from the emphysematous region and categorized into mild (≤5%), moderate (6–24%) and severe (25–60%). Results In group 1, patients with moderate and severe RES experienced slight decreases in postoperative FEV1, but increases in FEV1/FVC, compared to those with mild RES (p<0.01); however, this correlation was not observed in group 2. Post-treatment QOL was lower in patients with greater RES in all groups mainly due to dyspnea (p<0.05). Cox-regression analysis revealed that patients with higher RES had a significantly poorer survival in both surgical groups, with adjusted HRs of 1.41 and 1.43 for moderate RES and 1.63 and 2.04 for severe RES, respectively; however, this association was insignificant in the non-surgical group (adjusted HR of 0.99 for moderate/severe RES). Conclusions In surgically-treated patients with cancer in emphysematous region, RES is associated with postoperative changes in lung function. RES is also predictive of post-treatment QOL related to dyspnea in early-stage lung cancer. In both surgical groups, RES is an independent predictor of survival. PMID:28126539

Regional Emphysema Score Predicting Overall Survival, Quality of Life, and Pulmonary Function Recovery in Early-Stage Lung Cancer Patients.

PubMed

Dai, Jie; Liu, Ming; Swensen, Stephen J; Stoddard, Shawn M; Wampfler, Jason A; Limper, Andrew H; Jiang, Gening; Yang, Ping

2017-05-01

Pulmonary emphysema is a frequent comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on a patient's overall survival, quality of life (QOL), and recovery of pulmonary function in stage I to II lung cancer. Between 1997 and 2009, a total of 1073 patients were identified and divided into two surgical groups-cancer in the emphysematous (group 1 [n = 565]) and nonemphysematous (group 2 [n = 435]) regions-and one nonsurgical group (group 3 [n = 73]). RES was derived from the emphysematous region and categorized as mild (≤5%), moderate (6%-24%), or severe (25%-60%). In group 1, patients with a moderate or severe RES experienced slight decreases in postoperative forced expiratory volume in 1 second, but increases in the ratio of forced expiratory volume in 1 second to forced vital capacity compared with those with a mild RES (p < 0.01); however, this correlation was not observed in group 2. Posttreatment QOL was lower in patients with higher RESs in all groups, mainly owing to dyspnea (p < 0.05). Cox regression analysis revealed that patients with a higher RES had significantly poorer survival in both surgical groups, with adjusted hazard ratios of 1.41 and 1.43 for a moderate RES and 1.63 and 2.04 for a severe RES, respectively; however, this association was insignificant in the nonsurgical group (adjusted hazard ratio of 0.99 for a moderate or severe RES). In surgically treated patients with cancer in the emphysematous region, RES is associated with postoperative changes in lung function. RES is also predictive of posttreatment QOL related to dyspnea in early-stage lung cancer. In both surgical groups, RES is an independent predictor of survival. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In utero and early childhood exposure to arsenic decreases lung function in children

PubMed Central

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

2016-01-01

Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh

PubMed Central

Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

2013-01-01

Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry. PMID:24062297

Screening for Chlamydial Cervicitis in a Sexually Active University Population.

ERIC Educational Resources Information Center

Malotte, C. Kevin; And Others

1990-01-01

Enzyme-linked immunoabsorbent assays to detect chlamydial cervicitis were performed on samples from 1,320 sexually active university women. Seventy-five had positive tests. Demographic, history, symptom, and physical examination variables were insufficient to predict infection accurately. Concludes that screening during routine visits with this…

Early Life Wildfire Smoke Exposure Is Associated with Immune Dysregulation and Lung Function Decrements in Adolescence

PubMed Central

Black, Carolyn; Gerriets, Joan E.; Fontaine, Justin H.; Harper, Richart W.; Kenyon, Nicholas J.; Tablin, Fern; Schelegle, Edward S.

2017-01-01

The long-term health effects of wildfire smoke exposure in pediatric populations are not known. The objectives of this study were to determine if early life exposure to wildfire smoke can affect parameters of immunity and airway physiology that are detectable with maturity. We studied a mixed-sex cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008. Peripheral blood mononuclear cells (PBMCs) and pulmonary function measures were obtained when animals were approximately 3 years of age. PBMCs were cultured with either LPS or flagellin, followed by measurement of secreted IL-8 and IL-6 protein. PBMCs from a subset of female animals were also evaluated by Toll-like receptor (TLR) pathway mRNA analysis. Induction of IL-8 protein synthesis with either LPS or flagellin was significantly reduced in PBMC cultures from wildfire smoke–exposed female monkeys. In contrast, LPS- or flagellin-induced IL-6 protein synthesis was significantly reduced in PBMC cultures from wildfire smoke–exposed male monkeys. Baseline and TLR ligand–induced expression of the transcription factor, RelB, was globally modulated in PBMCs from wildfire smoke–exposed monkeys, with additional TLR pathway genes affected in a ligand-dependent manner. Wildfire smoke–exposed monkeys displayed significantly reduced inspiratory capacity, residual volume, vital capacity, functional residual capacity, and total lung capacity per unit of body weight relative to control animals. Our findings suggest that ambient wildfire smoke exposure during infancy results in sex-dependent attenuation of systemic TLR responses and reduced lung volume in adolescence. PMID:28208028

Early fundoplication is associated with slower decline in lung function after lung transplantation in patients with gastroesophageal reflux disease.

PubMed

Biswas Roy, Sreeja; Elnahas, Shaimaa; Serrone, Rosemarie; Haworth, Cassandra; Olson, Michael T; Kang, Paul; Smith, Michael A; Bremner, Ross M; Huang, Jasmine L

2018-06-01

Gastroesophageal reflux disease (GERD) is prevalent after lung transplantation. Fundoplication slows lung function decline in patients with GERD, but the optimal timing of fundoplication is unknown. We retrospectively reviewed patients who underwent fundoplication after lung transplantion at our center from April 2007 to July 2014. Patients were divided into 2 groups: early fundoplication (<6 months after lung transplantation) and late fundoplication (≥6 months after lung transplantation). Annual decline in percent predicted forced expiratory volume in 1 second (FEV 1 ) was analyzed. Of the 251 patients who underwent lung transplantation during the study period with available pH data, 86 (34.3%) underwent post-transplantation fundoplication for GERD. Thirty of 86 (34.9%) had early fundoplication and 56 of 86 (65.1%) had late fundoplication. Median time from lung transplantation to fundoplication was 4.6 months (interquartile range, 2.0-5.2) and 13.8 months (interquartile range, 9.0-16.1) for the early and late groups, respectively. The median DeMeester score was comparable between groups. One-, 3-, and 5-year actuarial survival rates in the early group were 90%, 70%, and 70%, respectively; in the late group, these rates were 91%, 66%, and 66% (log rank P = .60). Three- and 5-year percent predicted FEV 1 was lower in the late group by 8.9% (95% confidence interval, -30.2 to 12.38; P = .46) and 40.7% (95% confidence interval, -73.66 to -7.69; P = .019). A linear mixed model showed a 5.7% lower percent predicted FEV 1 over time in the late fundoplication group (P < .001). In this study, patients with early fundoplication had a higher FEV 1 5 years after lung transplantation. Early fundoplication might protect against GERD-induced lung damage in lung transplant recipients with GERD. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

In utero and early childhood exposure to arsenic decreases lung function in children.

PubMed

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

2015-04-01

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

PubMed

Tammemagi, Martin C; Schmidt, Heidi; Martel, Simon; McWilliams, Annette; Goffin, John R; Johnston, Michael R; Nicholas, Garth; Tremblay, Alain; Bhatia, Rick; Liu, Geoffrey; Soghrati, Kam; Yasufuku, Kazuhiro; Hwang, David M; Laberge, Francis; Gingras, Michel; Pasian, Sergio; Couture, Christian; Mayo, John R; Nasute Fauerbach, Paola V; Atkar-Khattra, Sukhinder; Peacock, Stuart J; Cressman, Sonya; Ionescu, Diana; English, John C; Finley, Richard J; Yee, John; Puksa, Serge; Stewart, Lori; Tsai, Scott; Haider, Ehsan; Boylan, Colm; Cutz, Jean-Claude; Manos, Daria; Xu, Zhaolin; Goss, Glenwood D; Seely, Jean M; Amjadi, Kayvan; Sekhon, Harmanjatinder S; Burrowes, Paul; MacEachern, Paul; Urbanski, Stefan; Sin, Don D; Tan, Wan C; Leighl, Natasha B; Shepherd, Frances A; Evans, William K; Tsao, Ming-Sound; Lam, Stephen

2017-11-01

Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer

Chronic lung disease of prematurity and early childhood wheezing: is foetal inflammatory response syndrome to blame?

PubMed

Dessardo, Nada Sindičić; Dessardo, Sandro; Mustać, Elvira; Banac, Srđan; Petrović, Oleg; Peter, Branimir

2014-09-01

Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. We aimed to investigate the perinatal and maternal risk factors involved in the development of chronic respiratory morbidity in preterm infants, with an emphasis on the importance of Foetal Inflammatory Response Syndrome (FIRS). Prospective cohort study. Demographic, antenatal, delivery and outcomes data were collected from 262 infants with less than 32 completed weeks of gestational age, over a 10-year period. Presence of chronic lung disease of prematurity and early childhood wheezing. In multivariate logistic regression analysis the presence of FIRS appears to be the most important risk factor for both, chronic lung disease of prematurity (OR 31.05, 95% CI 10.7-87.75, p<0.001) and early childhood wheezing (OR 5.63, 95% CI 2.42-13.05, p=0.01). In the alternative regression model for early childhood wheezing, with chronic lung disease included as a variable, the statistical significance of FIRS completely vanished (OR 1.15, 95% CI 0.39-3.34, p=0.79), whilst chronic lung disease became the most important risk factor (OR 23.45, 95% CI 8.5-63.25, p<0.001). Prenatal and early neonatal events are of utmost importance in the development of chronic respiratory symptoms in children. The influence of FIRS on the development of chronic respiratory symptoms goes far beyond its impact on gestational age and may be related to direct inflammation-mediated lung tissue damage. CLD appears to be an intermittent step on the way from FIRS to ECW. Copyright © 2014 Elsevier Ltd. All rights reserved.

In Vivo and Ex Vivo Imaging Reveals a Long-Lasting Chlamydial Infection in the Mouse Gastrointestinal Tract following Genital Tract Inoculation

PubMed Central

Zhang, Qi; Huang, Yumeng; Gong, Siqi; Yang, Zhangsheng; Sun, Xin; Schenken, Robert

2015-01-01

Intravaginal infection with Chlamydia muridarum in mice can ascend to the upper genital tract, resulting in hydrosalpinx, a pathological hallmark for tubal infertility in women infected with C. trachomatis. Here, we utilized in vivo imaging of C. muridarum infection in mice following an intravaginal inoculation and confirmed the rapid ascent of the chlamydial organisms from the lower to upper genital tracts. Unexpectedly, the C. muridarum-derived signal was still detectable in the abdominal area 100 days after inoculation. Ex vivo imaging of the mouse organs revealed that the long-lasting presence of the chlamydial signal was restricted to the gastrointestinal (GI) tract, which was validated by directly measuring the chlamydial live organisms and genomes in the same organs. The C. muridarum organisms spreading from the genital to the GI tracts were detected in different mouse strains and appeared to be independent of oral or rectal routes. Mice prevented from orally taking up excretions also developed the long-lasting GI tract infection. Inoculation of C. muridarum directly into the upper genital tract, which resulted in a delayed vaginal shedding of live organisms, accelerated the chlamydial spreading to the GI tract. Thus, we have demonstrated that the genital tract chlamydial organisms may use a systemic route to spread to and establish a long-lasting infection in the GI tract. The significance of the chlamydial spreading from the genital to GI tracts is discussed. PMID:26099591

Evaluation of intra- and extra-epithelial secretory IgA in chlamydial infections

PubMed Central

Armitage, Charles W; O’Meara, Connor P; Harvie, Marina C G; Timms, Peter; Wijburg, Odilia L; Beagley, Kenneth W

2014-01-01

Immunoglobulin A is an important mucosal antibody that can neutralize mucosal pathogens by either preventing attachment to epithelia (immune exclusion) or alternatively inhibit intra-epithelial replication following transcytosis by the polymeric immunoglobulin receptor (pIgR). Chlamydia trachomatis is a major human pathogen that initially targets the endocervical or urethral epithelium in women and men, respectively. As both tissues contain abundant secretory IgA (SIgA) we assessed the protection afforded by IgA targeting different chlamydial antigens expressed during the extra- and intra-epithelial stages of infection. We developed an in vitro model using polarizing cells expressing the murine pIgR together with antigen-specific mouse IgA, and an in vivo model using pIgR−/− mice. Secretory IgA targeting the extra-epithelial chlamydial antigen, the major outer membrane protein, significantly reduced infection in vitro by 24% and in vivo by 44%. Conversely, pIgR-mediated delivery of IgA targeting the intra-epithelial inclusion membrane protein A bound to the inclusion but did not reduce infection in vitro or in vivo. Similarly, intra-epithelial IgA targeting the secreted protease Chlamydia protease-like activity factor also failed to reduce infection. Together, these data suggest the importance of pIgR-mediated delivery of IgA targeting extra-epithelial, but not intra-epithelial, chlamydial antigens for protection against a genital tract infection. PMID:24827556

Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life.

PubMed

Bui, Dinh S; Lodge, Caroline J; Burgess, John A; Lowe, Adrian J; Perret, Jennifer; Bui, Minh Q; Bowatte, Gayan; Gurrin, Lyle; Johns, David P; Thompson, Bruce R; Hamilton, Garun S; Frith, Peter A; James, Alan L; Thomas, Paul S; Jarvis, Deborah; Svanes, Cecilie; Russell, Melissa; Morrison, Stephen C; Feather, Iain; Allen, Katrina J; Wood-Baker, Richard; Hopper, John; Giles, Graham G; Abramson, Michael J; Walters, Eugene H; Matheson, Melanie C; Dharmage, Shyamali C

2018-04-05

Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV 1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline

Chlamydia trachomatis today: treatment, detection, immunogenetics and the need for a greater global understanding of chlamydial disease pathogenesis

PubMed Central

Dean, Deborah

2012-01-01

Summary Chlamydia trachomatis is an important human pathogen causing a myriad of severe and debilitating diseases. While antibiotics have been a mainstay of treatment, there is increasing evidence for potential drug resistance, re-infection and persistent infections that require a reevaluation of treatment strategies. A critical need to address these issues will be a rapid, sensitive and cost-effect diagnostic that can be used for global screening, treatment and test-of-cure of infected individuals instead of empiric therapy that not only drives drug resistance but is not cost effective. This type of diagnostic would allow clinicians and researchers to evaluate the true incidence and prevalence of chlamydial infections in both developed and developing countries. There is extremely limited data on chlamydial sexually transmitted diseases (STD) in many developing countries including those in Central and South America. In addition, advancing our understanding of chlamydial disease pathogenesis will required an evaluation of host genetic susceptibility to infection and sequelae. We provide preliminary data on rates of chlamydial STDs and host genetic factors that predispose to infection among adolescent pregnant and non-pregnant commercial sex worker populations residing in Quito, Ecuador. PMID:20011691

Best practices in the treatment of early cystic fibrosis lung disease.

PubMed

Proesmans, Marijke

2017-02-01

For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

Emotional Problems, Quality of Life, and Symptom Burden in Patients With Lung Cancer.

PubMed

Morrison, Eleshia J; Novotny, Paul J; Sloan, Jeff A; Yang, Ping; Patten, Christi A; Ruddy, Kathryn J; Clark, Matthew M

2017-09-01

Lung cancer is associated with a greater symptom burden than other cancers, yet little is known about the prevalence of emotional problems and how emotional problems may be related to the physical symptom burden and quality of life in newly diagnosed patients with lung cancer. This study aimed to identify the patient and disease characteristics of patients with lung cancer experiencing emotional problems and to examine how emotional problems relate to quality of life and symptom burden. A total of 2205 newly diagnosed patients with lung cancer completed questionnaires on emotional problems, quality of life, and symptom burden. Emotional problems at diagnosis were associated with younger age, female gender, current cigarette smoking, current employment, advanced lung cancer disease, surgical or chemotherapy treatment, and a lower Eastern Cooperative Oncology Group performance score. Additionally, strong associations were found between greater severity of emotional problems, lower quality of life, and greater symptom burden. Certain characteristics place patients with lung cancer at greater risk for emotional problems, which are associated with a reduced quality of life and greater symptom burden. Assessment of the presence of emotional problems at the time of lung cancer diagnosis provides the opportunity to offer tailored strategies for managing negative mood, and for improving the quality of life and symptom burden management of patients with lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia.

PubMed

Piairo, Paulina; Moura, Rute S; Baptista, Maria João; Correia-Pinto, Jorge; Nogueira-Silva, Cristina

2018-01-01

Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH. © 2018 The Author(s). Published by S. Karger AG, Basel.

Rab11-family of interacting protein 2 associates with chlamydial inclusions through its Rab-binding domain and promotes bacterial multiplication.

PubMed

Leiva, Natalia; Capmany, Anahí; Damiani, María Teresa

2013-01-01

Chlamydia trachomatis, an obligate intracellular pathogen, survives within host cells in a special compartment named 'inclusion' and takes advantage of host vesicular transport pathways for its growth and replication. Rab GTPases are key regulatory proteins of intracellular trafficking. Several Rabs, among them Rab11 and Rab14, are implicated in chlamydial development. FIP2, a member of the Rab11-Family of Interacting Proteins, presents at the C-terminus a Rab-binding domain that interacts with both Rab11 and Rab14. In this study, we determined and characterized the recruitment of endogenous and GFP-tagged FIP2 to the chlamydial inclusions. The recruitment of FIP2 is specific since other members of the Rab11-Family of Interacting Proteins do not associate with the chlamydial inclusions. The Rab-binding domain of FIP2 is essential for its association. Our results indicate that FIP2 binds to Rab11 at the chlamydial inclusion membrane through its Rab-binding domain. The presence of FIP2 at the chlamydial inclusion favours the recruitment of Rab14. Furthermore, our results show that FIP2 promotes inclusion development and bacterial replication. In agreement, the silencing of FIP2 decreases the bacterial progeny. C. trachomatis likely recruits FIP2 to hijack host intracellular trafficking to redirect vesicles full of nutrients towards the inclusion. © 2012 Blackwell Publishing Ltd.

Noninvasive screening for genital chlamydial infections in asymptomatic men: Strategies and costs using a urine PCR assay

PubMed Central

Peeling, Rosanna W; Toye, Baldwin; Jessamine, Peter; Gemmill, Ian

1998-01-01

OBJECTIVE: To evaluate cost saving strategies to screen for genital chlamydial infection in men using polymerase chain reaction (PCR) technology. METHODS: Men with no urethral symptoms presenting to a sexually transmitted disease (STD) clinic were recruited. Study participants underwent a questionnaire interview. Urethral swabs were taken to perform a smear for polymorphonuclear leucocytes (PMN) and for the detection of Chlamydia trachomatis by culture and PCR. First-catch urine was collected for a leukocyte esterase test (LET) and PCR. RESULTS: C trachomatis infection was detected in 36 of 463 (7.8%) men. LET and PMN were positive in 10 (28%) and 12 (33%) infected men, respectively. Risk factors for chlamydial infection were younger than age 25 years, LET-positive, PMN-positive and STD contact (P<0.001). The direct cost of genital chlamydial infection in men in Canada has been previously estimated at $381/case. Based on a sensitivity of 90% for urine PCR, the estimated direct cost of testing all participants to detect 32 cases was $453/case. Using risk factors recommended in the Canadian STD Guidelines (age younger than 25 years, new partner, STD contact or unprotected sex), the same number of cases would have been detected by testing only 384 men at $376/case. Using age younger than 25 years or STD contact as the screening criterion, 78% of those infected would have been detected at $259/case, and no new cases would have been detected by adding LET-positive or PMN-positive as risk factors. CONCLUSION: Targeted screening for chlamydial infection using urine PCR assay and risk factors recommended in the Canadian guidelines could substantially reduce the cost of screening at a STD clinic setting. LET and PMN smear did not appear to be useful indicators of chlamydial infection in this population. PMID:22346549

Early Life Exposures and Cancer

Cancer.gov

Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

Extracorporeal life support in lung and heart-lung transplantation for pulmonary hypertension in adults.

PubMed

Kortchinsky, Talna; Mussot, Sacha; Rezaiguia, Saïda; Artiguenave, Margaux; Fadel, Elie; Stephan, François

2016-09-01

After bilateral lung and heart-lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life-threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30-day and 1-year survival rates in patients managed with vs without post-operative venoarterial ECLS in 2008-2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart-lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0-6] hours after surgery completion and for a median of 3.0 [2.0-8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart-lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early lung retrieval from traumatic brain-dead donors does not compromise outcomes following lung transplantation.

PubMed

Moreno, Paula; Alvarez, Antonio; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Cerezo, Francisco; Algar, Francisco Javier; Salvatierra, Angel

2013-06-01

To determine whether lung retrieval from traumatic donors performed within 24 h of brain death has a negative impact on early graft function and survival after lung transplantation (LT), when compared with those retrieved after 24 h. Review of lung transplants performed from traumatic donors over a 17-year period. Recipients were distributed into two groups: transplants from traumatic donor lungs retrieved within 24 h of brain death (Group A), and transplants from traumatic donor lungs retrieved after 24 h of brain death (Group B). Demographic data of donors and recipients, early graft function, perioperative complications and mortality were compared between both groups. Among 356 lung transplants performed at our institution, 132 were from traumatic donors (70% male, 30% female). Group A: 73 (55%); Group B: 59 (45%). There were 53 single, 77 double, and 2 combined LT. Indications were emphysema in 41 (31%), pulmonary fibrosis in 31 (23%), cystic fibrosis in 38 (29%), bronchiectasis in 9 (7%) and other indications in 13 patients (10%). Donor and recipient demographic data, need or cardiopulmonary bypass, postoperative complications and Intensive Care Unit and hospital stay did not differ between groups. Primary graft dysfunction (A vs B): 9 (16%) vs 13 (26%) P = 0.17. PaO2/FiO2 24 h post-transplant (A vs B): 303 mmHg vs 288 mmHg (P = 0.57). Number of acute rejection episodes (A vs B): 0.93 vs 1.49 (P = 0.01). Postoperative intubation time (A vs B): 99 vs 100 h (P = 0.99). 30-day mortality (A vs B): 7 (10%) vs 2 (3.5%) (P = 0.13). Freedom from bronchiolitis obliterans syndrome (A vs B): 82, 72, 37, 22 vs 78, 68, 42, 15%, at 3, 5, 10 and 15 years, respectively (P = 0.889). Survival (A vs B): 65, 54, 46, 42 and 27 vs 60, 50, 45, 43 and 29% at 3, 5, 7, 10 and 15 years, respectively (P = 0.937). In our experience, early lung retrieval after brain death from traumatic donors does not adversely affect early and long-term outcomes after LT.

Rac interacts with Abi-1 and WAVE2 to promote an Arp2/3-dependent actin recruitment during chlamydial invasion.

PubMed

Carabeo, Rey A; Dooley, Cheryl A; Grieshaber, Scott S; Hackstadt, Ted

2007-09-01

Chlamydiae are Gram-negative obligate intracellular pathogens to which access to an intracellular environment is fundamental to their development. Chlamydial attachment to host cells induces the activation of the Rac GTPase, which is required for the localization of WAVE2 at the sites of chlamydial entry. Co-immunoprecipitation experiments demonstrated that Chlamydia trachomatis infection promoted the interaction of Rac with WAVE2 and Abi-1, but not with IRSp53. siRNA depletion of WAVE2 and Abi-1 abrogated chlamydia-induced actin recruitment and significantly reduced the uptake of the pathogen by the depleted cells. Chlamydia invasion also requires the Arp2/3 complex as demonstrated by its localization to the sites of chlamydial attachment and the reduced efficiency of chlamydial invasion in cells overexpressing the VCA domain of the neural Wiskott-Aldrich syndrome protein. Thus, C. trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion.

SNPs in PTGS2 and LTA Predict Pain and Quality of Life in Long Term Lung Cancer Survivors

PubMed Central

Rausch, Sarah M.; Gonzalez, Brian D.; Clark, Matthew M.; Patten, Christi; Felten, Sara; Liu, Heshan; Li, Yafei; Sloan, Jeff; Yang, Ping

2015-01-01

PURPOSE Lung cancer survivors report the lowest quality of life relative to other cancer survivors. Pain is one of the most devastating, persistent, and incapacitating symptoms for lung cancer survivors. Prevalence rates vary with 80–100% of survivors experiencing cancer pain and healthcare costs are five times higher in cancer survivors with uncontrolled pain. Cancer pain often has a considerable impact on quality of life among cancer patients and cancer survivors. Therefore, early identification, and treatment is important. Although recent studies have suggested a relationship between single nucleotide polymorphisms (SNPs) in several cytokine and inflammation genes with cancer prognosis, associations with cancer pain are not clear. Therefore, the primary aim of this study was to identify SNPs related to pain in long term lung cancer survivors. PATIENTS AND METHODS Participants were enrolled in the Mayo Clinic Lung Cancer Cohort upon diagnosis of their lung cancer. 1149 Caucasian lung cancer survivors, (440 surviving < 3 years; 354 surviving 3–5 years; and 355 surviving> 5 years) completed study questionnaires and had genetic samples available. Ten SNPS from PTGS2 and LTA genes were selected based on the serum literature. Outcomes included pain, and quality of life as measured by the SF-8. RESULTS Of the 10 SNPs evaluated in LTA and PTGS2 genes, 3 were associated with pain severity (rs5277; rs1799964), social function (rs5277) and mental health (rs5275). These results suggested both specificity and consistency of these inflammatory gene SNPs in predicting pain severity in long term lung cancer survivors. CONCLUSION These results provide support for genetic predisposition to pain severity and may aid in identification of lung cancer survivors at high risk for morbidity and poor QOL. PMID:22464751

A deep learning method for early screening of lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Kunpeng; Jiang, Huiqin; Ma, Ling; Gao, Jianbo; Yang, Xiaopeng

2018-04-01

Lung cancer is the leading cause of cancer-related deaths among men. In this paper, we propose a pulmonary nodule detection method for early screening of lung cancer based on the improved AlexNet model. In order to maintain the same image quality as the existing B/S architecture PACS system, we convert the original CT image into JPEG format image by analyzing the DICOM file firstly. Secondly, in view of the large size and complex background of CT chest images, we design the convolution neural network on basis of AlexNet model and sparse convolution structure. At last we train our models on the software named DIGITS which is provided by NVIDIA. The main contribution of this paper is to apply the convolutional neural network for the early screening of lung cancer and improve the screening accuracy by combining the AlexNet model with the sparse convolution structure. We make a series of experiments on the chest CT images using the proposed method, of which the sensitivity and specificity indicates that the method presented in this paper can effectively improve the accuracy of early screening of lung cancer and it has certain clinical significance at the same time.

Respiratory physiology during early life.

PubMed

Stocks, J

1999-08-01

Despite the rapid adaptation to extrauterine life, the respiratory system of an infant is not simply a miniaturized version of that of an adult, since the rapid somatic growth that occurs during the first year of life is accompanied by major developmental changes in respiratory physiology. The highly compliant chest wall of the infant results in relatively low transpulmonary pressures at end expiration with increased tendency of the small peripheral airways to close during tidal breathing. This not only impairs gas exchange and ventilation-perfusion balance, particularly in dependent parts of the lung, but, together with the small absolute size of the airways, renders the infant and young child particularly susceptible to airway obstruction. Premature airways are highly compliant structures compared with those of mature newborns or adults. This increased compliance can cause airway collapse, resulting in increased airways resistance, flow limitation, poor gas exchange and increased work of breathing. Although there is clear evidence that airway reactivity is present from birth, its role in wheezing lower respiratory tract illnesses in young infants may be overshadowed by pre-existing abnormalities of airway geometry and lung mechanics, or by pathological changes such as airway oedema and mucus hypersecretion. Attempts to assess age-related changes in airway reactivity or response to aerosol therapy in the very young is confounded by changes in breathing patterns and the fact that infants are preferential nose breathers. There is increasing evidence that pre-existing abnormalities of respiratory function, associated with adverse events during foetal life (including maternal smoking during pregnancy), and familial predisposition to wheezing are important determinants of wheezing illnesses during the first years of life. This emphasizes the need to identify and minimize any factors that threaten the normal development of the lung during this critical period if

Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

PubMed Central

Abbosh, Christopher; Birkbak, Nicolai J.; Wilson, Gareth A.; Jamal-Hanjani, Mariam; Constantin, Tudor; Salari, Raheleh; Le Quesne, John; Moore, David A; Veeriah, Selvaraju; Rosenthal, Rachel; Marafioti, Teresa; Kirkizlar, Eser; Watkins, Thomas B K; McGranahan, Nicholas; Ward, Sophia; Martinson, Luke; Riley, Joan; Fraioli, Francesco; Al Bakir, Maise; Grönroos, Eva; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M.; Sponer, Nicole; Johnson, Diana; Laycock, Joanne; Shafi, Seema; Czyzewska-Khan, Justyna; Rowan, Andrew; Chambers, Tim; Matthews, Nik; Turajlic, Samra; Hiley, Crispin; Lee, Siow Ming; Forster, Martin D.; Ahmad, Tanya; Falzon, Mary; Borg, Elaine; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Hafez, Dina; Naik, Ashwini; Ganguly, Apratim; Kareht, Stephanie; Shah, Rajesh; Joseph, Leena; Quinn, Anne Marie; Crosbie, Phil; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-sellers, Melanie; Prakash, Vineet; Lester, Jason; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Oukrif, Dahmane; Akarca, Ayse U; Hartley, John A; Lowe, Helen L; Lock, Sara; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Elgar, Greg; Szallasi, Zoltan; Schwarz, Roland F; Herrero, Javier; Stewart, Aengus; Quezada, Sergio A; Peggs, Karl S.; Van Loo, Peter; Dive, Caroline; Lin, Jimmy; Rabinowitz, Matthew; Aerts, Hugo JWL; Hackshaw, Allan; Shaw, Jacqui A; Zimmermann, Bernhard G.; Swanton, Charles

2017-01-01

Summary The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies PMID:28445469

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

PubMed

Abbosh, Christopher; Birkbak, Nicolai J; Wilson, Gareth A; Jamal-Hanjani, Mariam; Constantin, Tudor; Salari, Raheleh; Le Quesne, John; Moore, David A; Veeriah, Selvaraju; Rosenthal, Rachel; Marafioti, Teresa; Kirkizlar, Eser; Watkins, Thomas B K; McGranahan, Nicholas; Ward, Sophia; Martinson, Luke; Riley, Joan; Fraioli, Francesco; Al Bakir, Maise; Grönroos, Eva; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M; Sponer, Nicole; Johnson, Diana; Laycock, Joanne; Shafi, Seema; Czyzewska-Khan, Justyna; Rowan, Andrew; Chambers, Tim; Matthews, Nik; Turajlic, Samra; Hiley, Crispin; Lee, Siow Ming; Forster, Martin D; Ahmad, Tanya; Falzon, Mary; Borg, Elaine; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Hafez, Dina; Naik, Ashwini; Ganguly, Apratim; Kareht, Stephanie; Shah, Rajesh; Joseph, Leena; Marie Quinn, Anne; Crosbie, Phil A; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean A; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-Sellers, Melanie; Prakash, Vineet; Lester, Jason F; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Oukrif, Dahmane; Akarca, Ayse U; Hartley, John A; Lowe, Helen L; Lock, Sara; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Elgar, Greg; Szallasi, Zoltan; Schwarz, Roland F; Herrero, Javier; Stewart, Aengus; Quezada, Sergio A; Peggs, Karl S; Van Loo, Peter; Dive, Caroline; Lin, C Jimmy; Rabinowitz, Matthew; Aerts, Hugo J W L; Hackshaw, Allan; Shaw, Jacqui A; Zimmermann, Bernhard G; Swanton, Charles

2017-04-26

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

A nested multiplex polymerase chain reaction assay for the differential identification of three zooanthroponotic chlamydial strains in porcine swab samples.

PubMed

Li, Yingguo; Wang, Yu; Nie, Fuping; Xiao, Jinwen; Wang, Guoming; Yuan, Ling; Li, Zhengguo

2011-07-01

Porcine chlamydial infection is an enzootic infectious disease caused by multiple members of the family Chlamydiaceae (e.g. Chlamydophila abortus, Chlamydia suis, and Chlamydophila pneumoniae). Rapid and accurate differentiation of these pathogens is critical in the control and prevention of disease. The aim of the current study was to develop a nested multiplex polymerase chain reaction (nmPCR) assay to simultaneously detect the 3 chlamydial pathogens in clinical samples. In the first round of the nmPCR, 1 pair of family-specific primers were used to amplify the 1,100 base pair (bp) fragment of chlamydial ompA gene. In the second round of the nmPCR, 4 inner primers were designed for Ch. abortus, C. suis, and Ch. pneumoniae. Each pathogen produced a specific amplicon with a size of 340 bp, 526 bp, and 267 bp respectively. The assay was sensitive and specific for detecting target pathogens in both cell cultures and clinical specimens. The results, incorporated with the improved rapid DNA extraction protocol, suggest that the nmPCR could be a promising assay for differential identification of different chlamydial strains in pigs.

Respiratory Symptoms, Sleep, and Quality of Life in Patients With Advanced Lung Cancer.

PubMed

Lou, Vivian W Q; Chen, Elaine J; Jian, Hong; Zhou, Zhen; Zhu, Jingfen; Li, Guohong; He, Yaping

2017-02-01

Maintenance of quality of life and symptom management are important in lung cancer therapy. To the author's knowledge, the interplay of respiratory symptoms and sleep disturbance in affecting quality of life in advanced lung cancer remains unexamined. The study was designed to examine the relationships among respiratory symptoms, sleep disturbance, and quality of life in patients with advanced lung cancer. A total of 128 patients with advanced lung cancer (from chest oncology inpatient-units in Shanghai, China) participated in the study. They completed two questionnaires: the Functional Assessment of Cancer Therapy-Lung and the Pittsburgh Sleep Quality Index. Symptomatic breathing difficulty, coughing, shortness of breath, and tightness in the chest were reported in 78.1%, 70.3%, 60.9%, and 60.2% of the patients, respectively. Sleep disturbance affected 62.5% of the patients. The patients with severe respiratory symptoms were more likely to be poor sleepers and to have a lower quality of life. After the covariates were controlled for, regression analysis showed that respiratory symptoms and sleep disturbance were significant indicators of quality of life. In addition, some of the effect of the respiratory symptoms on quality of life was mediated by sleep disturbance. Respiratory symptoms and sleep disturbance were common in the advanced lung cancer patients and had a negative impact on their quality of life; sleep disturbance may mediate the relationship between respiratory symptoms and quality of life. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Endotoxin Inhalation Alters Lung Development in Neonatal Mice

PubMed Central

Kulhankova, Katarina; George, Caroline L.S.; Kline, Joel N.; Darling, Melissa; Thorne, Peter S.

2012-01-01

Background Childhood asthma is a significant public health problem. Epidemiologic evidence suggests an association between childhood asthma exacerbations and early life exposure to environmental endotoxin. Although the pathogenesis of endotoxin-induced adult asthma is well studied, questions remain about the impact of environmental endotoxin on pulmonary responsiveness in early life. Methods We developed a murine model of neonatal/juvenile endotoxin exposures approximating those in young children and evaluated the lungs inflammatory and remodeling responses. Results Persistent lung inflammation induced by the inhalation of endotoxin in early life was demonstrated by the influx of inflammatory cells and pro-inflammatory mediators to the airways and resulted in abnormal alveolarization. Conclusions Results of this study advance the understanding of the impact early life endotoxin inhalation has on the lower airways, and demonstrates the importance of an experimental design that approximates environmental exposures as they occur in young children. PMID:22576659

Early Detection of Lung Cancer Using Nano-Nose - A Review

PubMed Central

Fernandes, M. P.; Venkatesh, S; Sudarshan, B. G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer. PMID:26628933

Early Detection of Lung Cancer Using Nano-Nose - A Review.

PubMed

Fernandes, M P; Venkatesh, S; Sudarshan, B G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer.

[Newer diagnostic procedures for chlamydial diseases (author's transl)].

PubMed

Edlinger, E; Ardoin, P

1982-06-17

Chlamydiales are bacteries showing a growth cycle unique among procaryotes. The two species Chlamydia trachomatis and Chlamydia psittaci are genetically very distant and their pathogenicity for man is very distinct. Human chlamydia infections by Chlamydia trachomatis are diseases chiefly sexually transmitted and their epidemiological importance is growing. The relationship between chlamydial infections, Reiter disease, and cat scratch disease are discussed. The various laboratory diagnostic procedures are reported, including the techniques and their indications; the method of choice is in the majority of cases the isolation of Chlamydia on cell culture.

Pediatric lung transplantation and end of life care in cystic fibrosis: Barriers and successful strategies.

PubMed

Dellon, Elisabeth; Goldfarb, Samuel B; Hayes, Don; Sawicki, Gregory S; Wolfe, Joanne; Boyer, Debra

2017-11-01

Pediatric lung transplantation has advanced over the years, providing a potential life-prolonging therapy to patients with cystic fibrosis. Despite this, many challenges in lung transplantation remain and result in worse outcomes than other solid organ transplants. As CF lung disease progresses, children and their caregivers are often simultaneously preparing for lung transplantation and end of life. In this article, we will discuss the current barriers to success in pediatric CF lung transplantation as well as approaches to end of life care in this population. © 2017 Wiley Periodicals, Inc.

Chlamydial variants differ in ability to ascend the genital tract in the guinea pig model of chlamydial genital infection.

PubMed

Yeruva, Laxmi; Bowlin, Anne K; Spencer, Nicole; Maurelli, Anthony T; Rank, Roger G

2015-08-01

An important question in the study of chlamydial genital tract disease is why some women develop severe upper tract disease while others have mild or even "silent" infections with or without pathology. Animal studies suggest that the pathological outcome of an infection is dependent upon both the composition of the infecting chlamydial population and the genotype of the host, along with host physiological effects, such as the cyclical production of reproductive hormones and even the size of the infecting inoculum or the number of repeated infections. In this study, we compared two variants of Chlamydia caviae, contrasting in virulence, with respect to their abilities to ascend the guinea pig genital tract. We then determined the effect of combining the two variants on the course of infection and on the bacterial loads of the two variants in the genital tract. Although the variants individually had similar infection kinetics in the cervix, SP6, the virulent variant, could be isolated from the oviducts more often and in greater numbers than the attenuated variant, AZ2. SP6 also elicited higher levels of interleukin 8 (IL-8) in the lower genital tract and increased leukocyte infiltration in the cervix and uterus compared to AZ2. When the two variants were combined in a mixed infection, SP6 outcompeted AZ2 in the lower genital tract; however, AZ2 was able to ascend the genital tract as readily as SP6. These data suggest that the ability of SP6 to elicit an inflammatory response in the lower genital tract facilitates the spread of both variants to the oviducts. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Quality of life in caregivers providing care for lung transplant candidates.

PubMed

Lefaiver, Cheryl A; Keough, Vicki A; Letizia, Marijo; Lanuza, Dorothy M

2009-06-01

Caregivers are essential members of the health care team who provide care, valued at more than $250 billion each year, to millions of persons who require assistance with health and daily care. Patients with respiratory diseases who are waiting for a lung transplant are required to have an identified caregiver. The caregivers are rarely studied. To explore the relationships among the health status of caregivers of lung transplant candidates, caregivers' reaction to caregiving, and caregivers' perceived quality of life. This descriptive study examined the quality of life of lung transplant caregivers from a multidimensional perspective. Twenty-nine dyads of lung transplant candidates and their caregivers were recruited from a Midwestern medical center. Data were collected by self-report: caregivers completed the Quality of Life Index, SF-12 health survey, Profile of Mood States-Short Form, and the Caregiver Reaction Assessment. Caregivers reported favorable levels of quality of life, physical health, and mood during the pretransplant waiting phase. However, problem areas for caregivers during this time included fatigue, depression, and the financial impact of the transplant. Data analyses indicated that depression, caregiver general health, impact on finances, and lack of family support had the greatest effect on caregivers' quality of life. Nurses are urged to recognize the role of caregivers in the transplant process, ask about and listen to caregivers' needs, and include caregivers in the plan of care.

Ex vivo lung perfusion.

PubMed

Reeb, Jeremie; Cypel, Marcelo

2016-03-01

Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Resolution of a life-threatening complication after lung radiofrequency ablation.

PubMed

Andreetti, Claudio; Maurizi, Giulio; Cassiano, Francesco; Rendina, Erino Angelo

2014-10-01

Lung radiofrequency ablation (RFA) is an option for the treatment of unresectable lung cancer. Clinical investigators have previously warned against severe complications associated with this procedure. We report a case of life-threatening complication after lung RFA for non-operable non-small-cell lung cancer consisting of pulmonary abscess evolving into a bronchopleural fistula, severe pneumothorax and septic pleuritis, which was successfully treated with a multimodal conservative approach. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The Impact of Protein Phosphorylation on Chlamydial Physiology

PubMed Central

Claywell, Ja E.; Matschke, Lea M.; Fisher, Derek J.

2016-01-01

Chlamydia are Gram negative bacterial pathogens responsible for disease in humans and economically important domesticated animals. As obligate intracellular bacteria, they must gain entry into a host cell where they propagate within a parasitophorous organelle that serves as an interactive interface between the bacterium and the host. Nutrient acquisition, growth, and evasion of host defense mechanisms occur from this location. In addition to these cellular and bacterial dynamics, Chlamydia differentiate between two morphologically distinct forms, the elementary body and reticulate body, that are optimized for either extracellular or intracellular survival, respectively. The mechanisms regulating and mediating these diverse physiological events remain largely unknown. Reversible phosphorylation, including classical two-component signaling systems, partner switching mechanisms, and the more recently appreciated bacterial Ser/Thr/Tyr kinases and phosphatases, has gained increasing attention for its role in regulating important physiological processes in bacteria including metabolism, development, and virulence. Phosphorylation modulates these events via rapid and reversible modification of protein substrates leading to changes in enzyme activity, protein oligomerization, cell signaling, and protein localization. The characterization of several conserved chlamydial protein kinases and phosphatases along with phosphoproteome analysis suggest that Chlamydia are capable of global and growth stage-specific protein phosphorylation. This mini review will highlight the current knowledge of protein phosphorylation in Chlamydia and its potential role in chlamydial physiology and, consequently, virulence. Comparisons with other minimal genome intracellular bacterial pathogens also will be addressed with the aim of illustrating the importance of this understudied regulatory mechanism on pathogenesis and the principle questions that remain unanswered. PMID:28066729

Early bronchiectasis in cystic fibrosis detected by surveillance CT.

PubMed

Pillarisetti, Naveen; Linnane, Barry; Ranganathan, Sarath

2010-08-01

There is emerging evidence that cystic fibrosis lung disease begins early in infancy. Newborn screening allows early detection and surveillance of pulmonary disease and the possibility of early intervention in this life-shortening condition. We report two children with cystic fibrosis who underwent a comprehensive assessment from diagnosis that included measurement of lung function, limited-slice high-resolution CT and BAL performed annually. Early aggressive surveillance enabled significant lung disease and bronchiectasis to be detected during the first few years of life and led to a change in management, highlighting a clinical role for CT scanning during the preschool years in children with cystic fibrosis.

Chlamydial infections in free-living birds

USGS Publications Warehouse

Brand, C.J.

1989-01-01

Most studies of chlamydial infections in free-living wild birds have been limited to surveys for the presence of Chlamydia psittaci or antibody to C psittaci and have largely been done in association with the identification of chlamydiosis in human beings, commercial fowl, or pet birds. The emphasis of these studies has been to determine the prevalence of infection and the potential role of wild birds in the spread of chlamydiae to domestic birds and human beings. Little is known about the epizootiology of chlamydiosis in free-living birds or its affect on their population dynamics. The following article is a summary of reported studies of chlamydiosis in free-living wild birds in relation to host range, ecologic aspects of transmission and maintenance, and the prevalence of disease.

Evaluation of an anti-chlamydial antibiotic therapy influence on asthma patients.

PubMed

Gryglicka, Beata; Wegrzyn-Szkutnik, Irena; Michnar, Marek; Mazur, Elzbieta; Niedźwiadek, Justyna; Milanowski, Janusz

2003-01-01

Chlamydia pneumoniae is one of the most frequent pathogens causing airways infections. Contribution of chronic chlamydial infection to the following diseases: asthma, POChP, coronary heart disease, abdominal aortic aneurysm, is particularly interesting. The connection between such infection and bronchial asthma was described in the literature in 1991. C. pneumoniae often causes asthma exacerbation; it is suggested that it also may be an etiologic factor of the disease. In a group of 55 subjects with chronic, stable bronchial asthma treated in the Pulmonary Department, serologic characteristic of C. pneumoniae infection was found in 34 patients (61,8%). Thirteen of these subjects agreed to participate in the study. They were divided into two groups; placebo was administered to the first one and azithromycin in a dose of 1000 mg once a week--to the other one. The research was conducted using the double blind trial method. Anti-chlamydial antibody level was evaluated before and after treatment. Spirometry tests as well as subjective estimation of physical fitness and dyspnoea degree were also determined. In comparison with 'the placebo group', statistically significant improvement in respiratory parameters 'in the treated group' was not ascertained.

Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

PubMed

Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

2015-05-01

The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

Early detection of cystic fibrosis lung disease: multiple‐breath washout versus raised volume tests

PubMed Central

Lum, Sooky; Gustafsson, Per; Ljungberg, Henrik; Hülskamp, Georg; Bush, Andrew; Carr, Siobhán B; Castle, Rosemary; Hoo, Ah‐fong; Price, John; Ranganathan, Sarath; Stroobant, John; Wade, Angie; Wallis, Colin; Wyatt, Hilary; Stocks, Janet

2007-01-01

Background Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple‐breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco–abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow‐volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV0.5 and FEF25–75 ) than boys (mean (95% CI girls–boys): –1.2 (–2.1 to −0.3) for FEV0.5 Z score; FEF25–75: –1.2 (–2.2 to −0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC. PMID:17121870

Changes in the Staphylococcus aureus Transcriptome during Early Adaptation to the Lung

PubMed Central

Chaffin, Donald O.; Taylor, Destry; Skerrett, Shawn J.; Rubens, Craig E.

2012-01-01

Staphylococcus aureus is a common inhabitant of the human nasopharynx. It is also a cause of life-threatening illness, producing a potent array of virulence factors that enable survival in normally sterile sites. The transformation of S. aureus from commensal to pathogen is poorly understood. We analyzed S. aureus gene expression during adaptation to the lung using a mouse model of S. aureus pneumonia. Bacteria were isolated by bronchoalveolar lavage after residence in vivo for up to 6 hours. S. aureus in vivo RNA transcription was compared by microarray to that of shake flask grown stationary phase and early exponential phase cells. Compared to in vitro conditions, the in vivo transcriptome was dramatically altered within 30 minutes. Expression of central metabolic pathways changed significantly in response to the lung environment. Gluconeogenesis (fbs, pckA) was down regulated, as was TCA cycle and fermentation pathway gene expression. Genes associated with amino acid synthesis, RNA translation and nitrate respiration were upregulated, indicative of a highly active metabolic state during the first 6 hours in the lung. Virulence factors regulated by agr were down regulated in vivo and in early exponential phase compared to stationary phase cells. Over time in vivo, expression of ahpCF, involved in H2O2 scavenging, and uspA, which encodes a universal stress regulator, increased. Transcription of leukotoxic α and β-type phenol-soluble modulins psmα1-4 and psmβ1-2 increased 13 and 8-fold respectively; hld mRNA, encoding δ-hemolysin, was increased 9-fold. These were the only toxins to be significantly upregulated in vivo. These data provide the first complete survey of the S. aureus transcriptome response to the mammalian airway. The results present intriguing contrasts with previous work in other in vitro and in vivo models and provide novel insights into the adaptive and temporal response of S. aureus early in the pathogenesis of pneumonia. PMID:22876285

Specific early fine structural changes in the lung following irradiation. [X rays; mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penney, D.P.; Rubin, P.

1977-01-01

The lungs of mice were irradiated with single and fractionated doses of 1000 R, 2000 R, and 3000 R and recovered 1 hr, 1 day, 1 week, and 1 month following exposure. Electron microscopy revealed early changes in the decrement of lamellar bodies of Type II pneumocytes and increased fibrous content and edema in the septal walls of all animals treated. Those lungs treated with fractionated doses of irradiation displayed more pronounced cellular damage than did singly-dosed lungs. It is proposed that these early changes may predict for subsequent atelectasis.

Discovery of chlamydial peptidoglycan reveals bacteria with murein sacculi but without FtsZ

NASA Astrophysics Data System (ADS)

Pilhofer, Martin; Aistleitner, Karin; Biboy, Jacob; Gray, Joe; Kuru, Erkin; Hall, Edward; Brun, Yves V.; Vannieuwenhze, Michael S.; Vollmer, Waldemar; Horn, Matthias; Jensen, Grant J.

2013-12-01

Chlamydiae are important pathogens and symbionts with unique cell biological features. They lack the cell-division protein FtsZ, and the existence of peptidoglycan (PG) in their cell wall has been highly controversial. FtsZ and PG together function in orchestrating cell division and maintaining cell shape in almost all other bacteria. Using electron cryotomography, mass spectrometry and fluorescent labelling dyes, here we show that some environmental chlamydiae have cell wall sacculi consisting of a novel PG type. Treatment with fosfomycin (a PG synthesis inhibitor) leads to lower infection rates and aberrant cell shapes, suggesting that PG synthesis is crucial for the chlamydial life cycle. Our findings demonstrate for the first time the presence of PG in a member of the Chlamydiae. They also present a unique example of a bacterium with a PG sacculus but without FtsZ, challenging the current hypothesis that it is the absence of a cell wall that renders FtsZ non-essential.

Predicting Later-Life Outcomes of Early-Life Exposures

EPA Science Inventory

Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

Cysts mark the early stage of metastatic tumor development in non-small cell lung cancer

PubMed Central

Thakur, Chitra; Rapp, Ulf R.; Rudel, Thomas

2018-01-01

Identifying metastatic tumor growth at an early stage has been one of the biggest challenges in the treatment of lung cancer. By genetic lineage tracing approach in a conditional model of Non-Small Cell Lung Cancer (NSCLC) in mice, we demonstrate that cystic lesions represent an early stage of metastatic invasion. We generated a mouse model for NSCLC which incorporated a heritable DsRed fluorescent tag driven by the ubiquitous CAG promoter in the alveolar type II cells of the lung. We found early cystic lesions in a secondary organ (liver) that lacked the expression of bona fide lung makers namely Scgb1a1 and surfactant protein C Sftpc and were DsRed positive hence identifying lung as their source of origin. This demonstrates the significant potential of alveolar type II cells in orchestrating the process of metastasis, rendering it as one of the target cell types of the lung of therapeutic importance in human NSCLC. PMID:29464089

Epidemiology of lung cancer prognosis: quantity and quality of life.

PubMed

Yang, Ping

2009-01-01

Primary lung cancer is very heterogeneous in its clinical presentation, histopathology, and treatment response; and like other diseases, the prognosis consists of two essential facets: survival and quality of life (QOL). Lung cancer survival is mostly determined by disease stage and treatment modality, and the 5-Year survival rate has been in a plateau of 15% for three decades. QOL is focused on life aspects that are affected by health conditions and medical interventions; the balance of physical functioning and suffering from treatment side effects has long been a concern of care providers as well as patients. Obviously needed are easily measurable biologic markers to stratify patients before treatment for optimal results in survival and QOL and to monitor treatment responses and toxicities. Targeted therapies toward the mechanisms of tumor development, growth, and metastasis are promising and actively translated into clinical practice. Long-term lung cancer (LTLC) survivors are people who are alive 5 Years after the diagnosis. Knowledge about the health and QOL in LTLC survivors is limited because outcome research in lung cancer has been focused mainly on short-term survival. The independent or combined effects of lung cancer treatment, aging, smoking and drinking, comorbid conditions, and psychosocial factors likely cause late effects, including organ malfunction, chronic fatigue, pain, or premature death among lung cancer survivors. New knowledge to be gained should help lung cancer survivors, their healthcare providers, and their caregivers by providing evidence for establishing clinical recommendations to enhance their long-term survival and health-related QOL.

Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer.

PubMed

Hinde, S; McKenna, C; Whyte, S; Peake, M D; Callister, M E J; Rogers, T; Sculpher, M

2015-06-30

Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the 'worried-well' population and the route of diagnosis that might occur as a result of the campaigns. The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of £13 660 and £18 173 per QALY gained, respectively. The scenarios found that increases in the 'worried-well' population may impact the cost-effectiveness conclusions. Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population.

Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer

PubMed Central

Hinde, S; McKenna, C; Whyte, S; Peake, M D; Callister, M E J; Rogers, T; Sculpher, M

2015-01-01

Background: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. Methods: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well' population and the route of diagnosis that might occur as a result of the campaigns. Results: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of £13 660 and £18 173 per QALY gained, respectively. The scenarios found that increases in the ‘worried-well' population may impact the cost-effectiveness conclusions. Conclusions: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population. PMID:26010412

Audit of the autoantibody test, EarlyCDT®-lung, in 1600 patients: an evaluation of its performance in routine clinical practice.

PubMed

Jett, James R; Peek, Laura J; Fredericks, Lynn; Jewell, William; Pingleton, William W; Robertson, John F R

2014-01-01

EarlyCDT(®)-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient. Clinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging. Six month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity=41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II. EarlyCDT-Lung has been extensively tested and validated in case-control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Liquid biopsy for lung cancer early detection.

PubMed

Santarpia, Mariacarmela; Liguori, Alessia; D'Aveni, Alessandro; Karachaliou, Niki; Gonzalez-Cao, Maria; Daffinà, Maria Grazia; Lazzari, Chiara; Altavilla, Giuseppe; Rosell, Rafael

2018-04-01

Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients. Novel sensitive and specific biomarkers for identification of high-risk subjects and early detection that can be used alternatively and/or complement current routine diagnostic procedures are needed. Liquid biopsy has recently demonstrated its clinical usefulness in advanced NSCLC as a surrogate of tissue biopsy for noninvasive assessment of specific genomic alterations, thereby providing prognostic and predictive information. Different biosources from liquid biopsy, including cell free circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs), have also been widely investigated for their potential role in lung cancer diagnosis. This review will provide an overview on the circulating biomarkers being evaluated for lung cancer detection, mainly focusing on results from most recent studies, the techniques developed to perform their assessment in blood and other biologic fluids and challenges in their clinical applications.

Liquid biopsy for lung cancer early detection

PubMed Central

Liguori, Alessia; D’Aveni, Alessandro; Karachaliou, Niki; Gonzalez-Cao, Maria; Daffinà, Maria Grazia; Lazzari, Chiara; Altavilla, Giuseppe; Rosell, Rafael

2018-01-01

Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients. Novel sensitive and specific biomarkers for identification of high-risk subjects and early detection that can be used alternatively and/or complement current routine diagnostic procedures are needed. Liquid biopsy has recently demonstrated its clinical usefulness in advanced NSCLC as a surrogate of tissue biopsy for noninvasive assessment of specific genomic alterations, thereby providing prognostic and predictive information. Different biosources from liquid biopsy, including cell free circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs), have also been widely investigated for their potential role in lung cancer diagnosis. This review will provide an overview on the circulating biomarkers being evaluated for lung cancer detection, mainly focusing on results from most recent studies, the techniques developed to perform their assessment in blood and other biologic fluids and challenges in their clinical applications. PMID:29780635

Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

PubMed Central

Prusty, Bhupesh K.; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

2012-01-01

Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance. PMID:23077614

Chlamydial infections in wildlife-conservation threats and/or reservoirs of 'spill-over' infections?

PubMed

Burnard, Delaney; Polkinghorne, Adam

2016-11-30

Members of the order Chlamydiales are biphasic intracellular pathogens known to cause disease in both humans and animals. As we learn more about the genetic diversity of this group of pathogens, evidence is growing that these bacteria infect a broader range of animal hosts than previously thought. Over 400 host species are now documented globally with the majority of these being wild animals. Given the impact of chlamydial infections on humans and domesticated animals, the identification of members of the order Chlamydiales in wildlife raises significant questions over a) their impact on animal health and b) the relationships to those strains also found in humans and domestic animals. In some species such as the iconic marsupial, the koala, the conservation impact is known with chlamydial infections associated with debilitating disease, however, in general, little is known about the pathogenic potential of Chlamydiae infecting most wildlife hosts. Accumulating evidence suggests contact with wild animals is a risk factor for infections in domestic animals and/or humans. Beyond the well-recognised zoonotic pathogen, Chlamydia psittaci, a range of studies have now reported traditional pathogens in the family Chlamydiaceae such as Chlamydia pecorum, Chlamydia suis, Chlamydia pneumoniae and Chlamydia abortus in wild animals. The spectre of cross-host transmission 'spill-over' and 'spill-back' in the epidemiology of infections is of potential concern, however, comprehensive epidemiological studies are lacking for most of these. Accurate evaluation of the significance of chlamydial infections in wildlife is otherwise hampered by i) the cross-sectional nature of most impact studies, ii) a lack of standardised diagnostic approaches, iii) limited study sizes, and iv) biases associated with opportunistic sampling. Copyright © 2016 Elsevier B.V. All rights reserved.

The airway microbiota in early cystic fibrosis lung disease.

PubMed

Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

2017-11-01

Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

Lung transplant recipients holding companion animals: impact on physical health and quality of life.

PubMed

Irani, S; Mahler, C; Goetzmann, L; Russi, E W; Boehler, A

2006-02-01

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

Chlamydial and gonococcal infection in men without polymorphonuclear leukocytes on gram stain: implications for diagnostic approach and management.

PubMed

Geisler, William M; Yu, Shuying; Hook, Edward W

2005-10-01

Gram stain is used to detect urethral inflammation, suggestive of infection, in men and guide therapeutic decisions. In the absence of signs, symptoms, or polymorphonuclear leukocytes (PMNs) on urethral Gram stain, treatment and sometimes testing is deferred. Determine the proportion of men with chlamydia or gonorrhea diagnosed by nucleic acid amplification testing (NAAT) or culture who lack Gram stain evidence of inflammation and compare their clinical characteristics to men with inflammation. Records from 2629 men presenting for routine sexually transmitted disease care with urethral PMN count and NAAT data were retrospectively analyzed. A subpopulation tested by NAAT and culture was analyzed. Men receiving antibiotics within the prior month or those reporting a sexual partner with trichomoniasis were excluded. Among 2266 eligible men, 353 (16%) had chlamydia and 462 (20%) had gonorrhea. Among chlamydia-infected men, PMNs per oil-immersion field (oif) on Gram stain were > or =5 in 291 (82%), 1 to 4 in 20 (6%), and none in 42 (12%). In men with gonorrhea, PMNs/oif were > or =5 in 433 (94%), 1 to 4 in 6 (1%), and none in 23 (5%). Urethral symptoms, discharge, and/or > or =5 PMNs/oif were absent in 47 (13%) and 22 (5%) of chlamydial and gonococcal infections, respectively (including no PMNs/oif and 1-4 PMNs/oif). None of these 47 chlamydial-infected men and only 4 of 22 men with gonorrhea received therapy at the time of initial examination. Twelve percent of chlamydial and 5% of gonococcal infections had no Gram stain evidence of urethral inflammation. Absence of symptoms and discharge is not uncommon in chlamydial infection detected by NAAT, and without testing, many infections will go untreated, furthering the possibility of complications or partner transmission.

Apoptosis Modulation in the Immune System Reveals a Role of Neutrophils in Tissue Damage in a Murine Model of Chlamydial Genital Infection.

PubMed

Zortel, Tom; Schmitt-Graeff, Annette; Kirschnek, Susanne; Häcker, Georg

2018-05-05

Chlamydial infection frequently causes damage to the female genital tract. The precise mechanisms of chlamydial clearance and tissue damage are unknown, but studies suggest immunopathology with a particular role of neutrophils. The goal of this study was to understand the contribution of the immune system, in particular neutrophils. Using Chlamydia muridarum, we infected mice with a prolonged immune response due to expression of B-cell lymphoma 2 (Bcl-2) in hematopoietic cells (Bcl-2 mice), and mice where mature neutrophils are lacking due to the deletion of Myeloid cell leukemia 1 (Mcl-1) in myeloid cells (LysM-cre-mcl-1-flox mice; Mcl-1 mice). We monitored bacterial clearance, cellular infiltrate, and long-term tissue damage. Both mutant strains showed slightly delayed clearance of the acute infection. Bcl-2 mice had a strongly increased inflammatory infiltrate concerning almost all cell lineages. The infection of Bcl-2 mice caused increased tissue damage. The loss of neutrophils in Mcl-1 mice was associated with substantial quantitative and qualitative alterations of the inflammatory infiltrate. Mcl-1 mice had higher chlamydial burden and reduced tissue damage, including lower incidence of hydrosalpinx and less uterine dilation. Inhibition of apoptosis in the hematopoietic system increases inflammation and tissue damage. Neutrophils have broad functions, including a role in chlamydial clearance and in tissue destruction.

Early-life origins of life-cycle well-being: research and policy implications.

PubMed

Currie, Janet; Rossin-Slater, Maya

2015-01-01

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the life cycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socioeconomic status. However, there is some variation in the degree to which current policies in the United States are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early-childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited.

Upregulation of endothelin receptors A and B in the nitrofen induced hypoplastic lung occurs early in gestation.

PubMed

Dingemann, Jens; Doi, Takashi; Ruttenstock, Elke; Puri, Prem

2010-01-01

Pulmonary hypoplasia and persistent pulmonary hypertension (PPH) aggravate clinical courses in congenital diaphragmatic hernia (CDH). Endothelin 1 enhances PPH by vasoconstriction and proliferation of vessel walls. Up-regulation of pulmonary Endothelin Receptors A and B (EDNRA, EDNRB) has been reported in human CDH and animal models, but the onset of those alterations during lung development remains unclear. We hypothesized that pulmonary expression of EDNRA and EDNRB is up-regulated at early gestational stages in the nitrofen model. Pregnant rats were exposed to nitrofen or vehicle on gestational day 9 (D9). Embryos were sacrificed on D15, D18 and D21 and divided into nitrofen- and control group. Pulmonary RNA was extracted and mRNA levels of EDNRA and EDNRB were determined by real-time PCR. Immunohistochemistry for protein expression of both receptors was performed. mRNA levels of EDNRA and EDNRB were significantly increased in the nitrofen group on D15, D18 and D21. Immunohistochemistry revealed increased pulmonary vascular expression of EDNRA and EDNRB compared to controls. Altered expression of EDNRA and EDNRB is an early event in lung morphogenesis in the nitrofen model. We speculate that pulmonary arteries in CDH become excessively muscularised in early fetal life, becoming unable to adapt normally at birth.

Impact of micro-environmental changes on respiratory tract infections with intracellular bacteria.

PubMed

Shima, Kensuke; Coopmeiners, Jonas; Graspeuntner, Simon; Dalhoff, Klaus; Rupp, Jan

2016-11-01

Community-acquired pneumonia is caused by intra- and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia pneumoniae is an obligate intracellular pathogen that is highly sensitive to micro-environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon-γ levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular C. pneumoniae. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body. © 2016 Federation of European Biochemical Societies.

Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

PubMed

Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

2017-07-20

Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

Exogenous determinants of early-life conditions, and mortality later in life.

PubMed

van den Berg, Gerard J; Doblhammer, Gabriele; Christensen, Kaare

2009-05-01

We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather indicators, and demographic indicators. We argue that these features can only affect high-age mortality by way of the individual early-life conditions. Moreover, they are exogenous from the individual point of view, which is a methodological advantage compared to the use of unique characteristics of the newborn individual or his or her family or household as early-life indicators. We collected national annual time-series data on the above-mentioned indicators, and we combine these to the individual data records from the Danish Twin Registry covering births in 1873-1906. The empirical analyses (mostly based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life.

[Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

PubMed

Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

2017-02-20

Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

Expression of Iroquois genes is up-regulated during early lung development in the nitrofen-induced pulmonary hypoplasia.

PubMed

Doi, Takashi; Lukošiūtė, Aušra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2011-01-01

Iroquois homeobox (Irx) genes have been implicated in the early lung morphogenesis of vertebrates. Irx1-3 and Irx5 gene expression is seen in fetal lung in rodents up to day (D) 18.5 of gestation. Fetal lung in Irx knockdown mice shows loss of mesenchyme and dilated airspaces, whereas nitrofen-induced hypoplastic lung displays thickened mesenchyme and diminished airspaces. We hypothesized that the Irx genes are up-regulated during early lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed either to olive oil or nitrofen on D9. Fetal lungs harvested on D15 were divided into control and nitrofen groups; and the lungs harvested on D18 were divided into control, nitrofen without congenital diaphragmatic hernia (CDH[-]), and nitrofen with CDH (CDH[+]). Irx gene expression levels were analyzed by reverse transcriptase polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of Irx family. Pulmonary Irx1-3 and Irx5 messenger RNA expression levels were significantly up-regulated in nitrofen group compared with controls at D15. On D15, Irx immunoreactivity was increased in nitrofen-induced hypoplastic lung compared with controls. Overexpression of Irx genes in the early lung development may cause pulmonary hypoplasia in the nitrofen CDH model by inducing lung dysmorphogenesis with thickened mesenchyme and diminished airspaces. Copyright © 2011 Elsevier Inc. All rights reserved.

Early Life Stages

EPA Pesticide Factsheets

Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

Lung Cancers Associated with Cystic Airspaces: Underrecognized Features of Early Disease.

PubMed

Sheard, Sarah; Moser, Joanna; Sayer, Charlie; Stefanidis, Konstantinos; Devaraj, Anand; Vlahos, Ioannis

2018-01-01

Early lung cancers associated with cystic airspaces are increasingly being recognized as a cause of delayed diagnoses-owing to data gathered from screening trials and encounters in routine clinical practice as more patients undergo serial imaging. Several morphologic subtypes of cancers associated with cystic airspaces exist and can exhibit variable patterns of progression as the solid elements of the tumor grow. Current understanding of the pathogenesis of these malignancies is limited, and the numbers of cases reported in the literature are small. However, several tumor cell types are represented in these lesions, with adenocarcinoma predominating. The features of cystic airspaces differ among cases and include emphysematous bullae, congenital or fibrotic cysts, subpleural blebs, bronchiectatic airways, and distended distal airspaces. Once identified, these cystic lesions pose management challenges to radiologists in terms of distinguishing them from benign mimics of cancer that are commonly seen in patients who also are at increased risk of lung cancer. Rendering a definitive tissue-based diagnosis can be difficult when the lesions are small, and affected patients tend to be in groups that are at higher risk of requiring biopsy or resection. In addition, the decision to monitor these cases can add to patient anxiety and cause the additional burden of strained departmental resources. The authors have drawn from their experience, emerging evidence from international lung cancer screening trials, and large databases of lung cancer cases from other groups to analyze the prevalence and evolution of lung cancers associated with cystic airspaces and provide guidance for managing these lesions. Although there are insufficient data to support specific management guidelines similar to those for managing small solid and ground-glass lung nodules, these data and guidelines should be the direction for ongoing research on early detection of lung cancer. © RSNA, 2018.

Experimental Lung Cancer Drug Shows Early Promise | Poster

Cancer.gov

By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for

Application of a High Throughput Method of Biomarker Discovery to Improvement of the EarlyCDT®-Lung Test

PubMed Central

Macdonald, Isabel K.; Murray, Andrea; Healey, Graham F.; Parsy-Kowalska, Celine B.; Allen, Jared; McElveen, Jane; Robertson, Chris; Sewell, Herbert F.; Chapman, Caroline J.; Robertson, John F. R.

2012-01-01

Background The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)). Methods and Findings Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7). Conclusion This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT­-Lung test, and so further aid the early detection of lung cancer. PMID:23272083

Regulatory parameters of the lung immune response during the early phase of experimental trichinellosis.

PubMed

Falduto, Guido H; Vila, Cecilia C; Saracino, María P; Gentilini, María V; Venturiello, Stella M

2016-11-15

Parasitic infection caused by Trichinella spiralis provokes an early stimulation of the mucosal immune system which causes an allergic inflammatory response in the lungs. The present work was intended to characterize the kinetics of emergence of regulatory parameters in Wistar rat lungs during this early inflammatory response, between days 0 and 13p.i. The presence of regulatory cells such as regulatory T cells (Tregs) and alternatively activated macrophages (AAM) was analyzed in lung cell suspensions. Moreover, a regulatory cytokine (TGF-β) was studied in lung tissue extracts. Considering that newborn larvae (NBL) travel along the pulmonary microvasculature, the ability of this parasite stage to modulate the activation of lung macrophages was evaluated. For this purpose, lung macrophages from non-infected or infected rats (day 6p.i.) were cultured with live or dead NBL. Arginase activity (characteristic of AAM) and nitric oxide (NO produced by iNOS, characteristic of classical activated macrophages) were measured after 48h. Our results revealed a significant increase in the percentage of Tregs on days 6 and 13p.i., arginase activity on day 13p.i. and TGF-β levels on days 6 and 13p.i. Lung macrophages from non-infected rats cultured with live NBL showed a significant increase in arginase activity and NO levels. Live and dead NBL induced a significant increase in arginase activity in lung macrophages from infected rats. Only live NBL significantly increased NO levels in these macrophages. The present work demonstrates for the first time, the emergence of regulatory parameters in the early lung immune response during T. spiralis infection. The immumodulatory properties exerted by NBL during its passage through this organ could be the cause of such regulation. Moreover, we have shown the ability of NBL to activate macrophages from the lung parenchyma by the classical and alternative pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

Early palliative care in advanced lung cancer: a qualitative study.

PubMed

Yoong, Jaclyn; Park, Elyse R; Greer, Joseph A; Jackson, Vicki A; Gallagher, Emily R; Pirl, William F; Back, Anthony L; Temel, Jennifer S

2013-02-25

BACKGROUND Early ambulatory palliative care (PC) is an emerging practice, and its key elements have not been defined. We conducted a qualitative analysis of data from a randomized controlled trial that demonstrated improved quality of life, mood, and survival in patients with newly diagnosed metastatic non-small cell lung cancer who received early PC integrated with standard oncologic care vs standard oncologic care alone. Our objectives were to (1) identify key elements of early PC clinic visits, (2) explore the timing of key elements, and (3) compare the content of PC and oncologic visit notes at the critical time points of clinical deterioration and radiographic disease progression. METHODS We randomly selected 20 patients who received early PC and survived within 4 periods: less than 3 months (n = 5), 3 to 6 months (n = 5), 6 to 12 months (n = 5), and 12 to 24 months (n = 5). We performed content analysis on PC and oncologic visit notes from the electronic health records of these patients. RESULTS Addressing symptoms and coping were the most prevalent components of the PC clinic visits. Initial visits focused on building relationships and rapport with patients and their families and on illness understanding, including prognostic awareness. Discussions about resuscitation preferences and hospice predominantly occurred during later visits. Comparing PC and oncologic care visits around critical time points, both included discussions about symptoms and illness status; however, PC visits emphasized psychosocial elements, such as coping, whereas oncologic care visits focused on cancer treatment and management of medical complications. CONCLUSIONS Early PC clinic visits emphasize managing symptoms, strengthening coping, and cultivating illness understanding and prognostic awareness in a responsive and time-sensitive model. During critical clinical time points, PC and oncologic care visits have distinct features that suggest a key role for PC involvement and enable

Antenatal vitamin A administration attenuates lung hypoplasia by interfering with early instead of late determinants of lung underdevelopment in congenital diaphragmatic hernia.

PubMed

Baptista, Maria J; Melo-Rocha, Gustavo; Pedrosa, Carla; Gonzaga, Sílvia; Teles, Antónia; Estevão-Costa, José; Areias, José C; Flake, Alan W; Leite-Moreira, Adelino F; Correia-Pinto, Jorge

2005-04-01

Early and late lung underdevelopment in congenital diaphragmatic hernia (CDH) is likely caused by nonmechanical (directly mediated by nitrofen) and mechanical (mediated by thoracic herniation) factors, respectively. The authors investigated if vitamin A enhances lung growth because of effects on both early and late determinants of lung hypoplasia. Twenty-seven pregnant Wistar rats were exposed on embryonic day (E)9.5 to 100 mg of nitrofen or just olive oil. From nitrofen-exposed pregnant rats, 12 were treated at day 9.5 or 18.5 with 15,000 IU of vitamin A. Lungs were harvested at E18, E20, and E22, weighed, and analyzed for DNA and protein contents. Left and/or right lung hypoplasia was estimated by assessment of the ratios of lung to body weight and left to right lung weight. Fetuses were assigned to 5 experimental groups: baseline (exposed neither to nitrofen nor vitamin A), nitrofen (exposed to nitrofen without CDH), CDH (exposed to nitrofen with CDH), nitr+vitA (exposed to nitrofen without CDH and treated with vitamin A), and CDH+vitA (exposed to nitrofen with CDH and treated with vitamin A). Incidence of hernia was significantly reduced in fetuses treated with vitamin A. When vitamin A was administered at E9.5, the authors observed similar effect on lung hypoplasia measured through ratio of lung to body weight at E18 in the nitrofen and CDH groups (nitrofen 1.92% +/- 0.05%, CDH 1.92% +/- 0.04%), whereas lung hypoplasia was attenuated relative to baseline (2.45% +/- 0.05%) in 5% and 4% in nitrofen (nitr+vitA 2.05% +/- 0.03%) and CDH (CDH+vitA 2.08% +/- 0.04%) groups, respectively. At E20, lung hypoplasia was increased in CDH compared with nitrofen groups (nitrofen 2.52% +/- 0.1%, CDH 2.39% +/- 0.05%), whereas vitamin A attenuated lung hypoplasia, in relation to baseline (3.20% +/- 0.07%), 14% in both nitrofen-exposed groups (nitr+vitA 2.96% +/- 0.03%, CDH+vitA 2.83% +/- 0.03%). At E22, lung hypoplasia was significantly higher in CDH group than nitrofen group

Early Life Lung Antioxidant Levels and Response to Ozone: Influence of Sex and Maturation in Wistar Rats

EPA Science Inventory

Abstract. Epidemiologic studies of air pollution effects on respiratory health report significant modification by sex. Studies of children suggest stronger effects among boys in early life and girls in later childhood. In adults, particularly the elderly, studies report stronger...

Early-life nutritional effects on the female reproductive system.

PubMed

Chan, K A; Tsoulis, M W; Sloboda, D M

2015-02-01

There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

Health-related quality of life questionnaires in lung cancer trials: a systematic literature review

PubMed Central

2013-01-01

Background Lung cancer is one of the leading causes of cancer deaths. Treatment goals are the relief of symptoms and the increase of overall survival. With the rising number of treatment alternatives, the need for comparable assessments of health-related quality of life (HRQoL) parameters grows. The aim of this paper was to identify and describe measurement instruments applied in lung cancer patients under drug therapy. Methods We conducted a systematic literature review at the beginning of 2011 using the electronic database Pubmed. Results A total of 43 studies were included in the review. About 17 different measurement instruments were identified, including 5 generic, 5 cancer-specific, 4 lung cancer-specific and 3 symptom-specific questionnaires. In 29 studies at least 2 instruments were used. In most cases these were cancer and lung cancer-specific ones. The most frequently used instruments are the EORTC QLQ-C30 and its lung cancer modules LC13 or LC17. Only 5 studies combined (lung) cancer-specific questionnaires with generic instruments. Conclusions The EORTC-C30 and EORTC-LC13 are the most frequently used health-related quality of life measurement instruments in pharmacological lung cancer trials. PMID:23680096

The Chlamydial Inclusion Preferentially Intercepts Basolaterally Directed Sphingomyelin-Containing Exocytic Vacuoles

PubMed Central

Moore, Elizabeth R.; Fischer, Elizabeth R.; Mead, David J.; Hackstadt, Ted

2010-01-01

Chlamydiae replicate intracellularly within a unique vacuole termed the inclusion. The inclusion circumvents classical endosomal/lysosomal pathways but actively intercepts a subset of Golgi-derived exocytic vesicles containing sphingomyelin (SM) and cholesterol. To further examine this interaction, we developed a polarized epithelial cell model to study vectoral trafficking of lipids and proteins to the inclusion. We examined seven epithelial cell lines for their ability to form single monolayers of polarized cells and support chlamydial development. Of these cell lines, polarized colonic mucosal C2BBe1 cells were readily infected with Chlamydia trachomatis and remained polarized throughout infection. Trafficking of (6-((N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)hexanoyl)sphingosine) (NBD-C6-ceramide) and its metabolic derivatives, NBD-glucosylceramide (GlcCer) and NBD-SM, was analyzed. SM was retained within L2-infected cells relative to mock-infected cells, correlating with a disruption of basolateral SM trafficking. There was no net retention of GlcCer within L2-infected cells and purification of C. trachomatis elementary bodies from polarized C2BBe1 cells confirmed that bacteria retained only SM. The chlamydial inclusion thus appears to preferentially intercept basolaterally-directed SM-containing exocytic vesicles, suggesting a divergence in SM and GlcCer trafficking. The observed changes in lipid trafficking were a chlamydia-specific effect because Coxiella burnetii-infected cells revealed no changes in GlcCer or SM polarized trafficking. PMID:18778406

Early-Life Origins of Life-Cycle Well-Being: Research and Policy Implications

ERIC Educational Resources Information Center

Currie, Janet; Rossin-Slater, Maya

2015-01-01

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population…

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

PubMed

Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

2013-11-01

Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

Preventing Obesity Across Generations: Evidence for Early Life Intervention.

PubMed

Haire-Joshu, Debra; Tabak, Rachel

2016-01-01

To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life.

Preventing Obesity Across Generations: Evidence for Early Life Intervention

PubMed Central

Haire-Joshu, Debra; Tabak, Rachel

2017-01-01

To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life. PMID:26989828

A developmental perspective on early-life exposure to neurotoxicants.

PubMed

Bellinger, David C; Matthews-Bellinger, Julia A; Kordas, Katarzyna

2016-09-01

Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective. The goal of this paper is to describe the key principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures. Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention. Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades. Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparing azithromycin and doxycycline for the treatment of rectal chlamydial infection: a retrospective cohort study

PubMed Central

Khosropour, Christine M.; Dombrowski, Julia C.; Barbee, Lindley A.; Manhart, Lisa E.; Golden, Matthew R.

2015-01-01

Background Centers for Disease Control and Prevention (CDC) guidelines recommend azithromycin or doxycycline for treatment of rectal chlamydial infection. Methods We created a retrospective cohort of male patients diagnosed with rectal chlamydia 1993-2012 at a sexually transmitted disease clinic in Seattle, Washington. Men were included in the analysis if they were treated with azithromycin (1g single dose) or doxycycline (100mg BID x 7 days) within 60 days of chlamydia diagnosis and returned for repeat testing 14-180 days post-treatment. We compared the risk of persistent/recurrent rectal chlamydial infection among recipients of the two drug regimens using four follow-up testing time intervals (14 to 30, 60, 90, and 180 days). Results Of 1,835 cases of rectal chlamydia diagnosed in the study period, 1,480 (81%) were treated with azithromycin or doxycycline without a second drug active against C. trachomatis. Of these, 407 (33%) of 1231 azithromycin-treated men and 95 (38%) of 249 doxycycline-treated men were re-tested 14-180 days after treatment (P=0.12); 88 (22%) and 8 (8%), respectively, had persistent/recurrent infection (P=0.002). Persistent/recurrent infection was higher among men treated with azithromycin compared to doxycycline at 14-30 days (4/53 (8%) vs. 0/20 (0%)), 14-60 days (23/136 (17%) vs. 0/36 (0%)), and 14-90 days (50/230 (22%) vs. 2/56 (4%)). In multivariate analysis, azithromycin-treated men had a significantly higher risk of persistent/recurrent infection in the 14-90 days (aRR=5.2, 95% CI=1.3-21.0) and 14-180 days (aRR=2.4, 95% CI=1.2-4.8) after treatment. Conclusions These data suggest that doxycycline may be more effective than azithromycin in the treatment of rectal chlamydial infections. PMID:24413484

Progress and prospects of early detection in lung cancer

PubMed Central

Blandin Knight, Sean; Crosbie, Phil A.; Balata, Haval; Chudziak, Jakub; Hussell, Tracy; Dive, Caroline

2017-01-01

Lung cancer is the leading cause of cancer-related death in the world. It is broadly divided into small cell (SCLC, approx. 15% cases) and non-small cell lung cancer (NSCLC, approx. 85% cases). The main histological subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma, with the presence of specific DNA mutations allowing further molecular stratification. If identified at an early stage, surgical resection of NSCLC offers a favourable prognosis, with published case series reporting 5-year survival rates of up to 70% for small, localized tumours (stage I). However, most patients (approx. 75%) have advanced disease at the time of diagnosis (stage III/IV) and despite significant developments in the oncological management of late stage lung cancer over recent years, survival remains poor. In 2014, the UK Office for National Statistics reported that patients diagnosed with distant metastatic disease (stage IV) had a 1-year survival rate of just 15–19% compared with 81–85% for stage I. PMID:28878044

Experimental Lung Cancer Drug Shows Early Promise | Poster

Cancer.gov

By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for safety and efficacy in Phase I and II clinical trials.

Good daily habits during the early stages of life determine success throughout life.

PubMed

Kohyama, Jun

2016-01-01

This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.

The Early Years: "Life" Science

ERIC Educational Resources Information Center

Ashbrook, Peggy

2013-01-01

Talking about death as part of a life cycle is often ignored or spoken about in hushed tones in early childhood. Books with "life cycle" in the title often do not include the death of the living organism in the information about the cycle. The concept of a complete life cycle does not appear in "A Framework for K-12 Science…

[Treatment of non-small cell lung carcinoma in early stages].

PubMed

Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

2013-12-01

Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Lung cancer: diagnosis, treatment principles, and screening.

PubMed

Latimer, Kelly M; Mott, Timothy F

2015-02-15

Lung cancer is classified histologically into small cell and non-small cell lung cancers. The most common symptoms of lung cancer are cough, dyspnea, hemoptysis, and systemic symptoms such as weight loss and anorexia. High-risk patients who present with symptoms should undergo chest radiography. If a likely alternative diagnosis is not identified, computed tomography and possibly positron emission tomography should be performed. If suspicion for lung cancer is high, a diagnostic evaluation is warranted. The diagnostic evaluation has three simultaneous steps (tissue diagnosis, staging, and functional evaluation), all of which affect treatment planning and determination of prognosis. The least invasive method possible should be used. The diagnostic evaluation and treatment of a patient with lung cancer require a team of specialists, including a pulmonologist, medical oncologist, radiation oncologist, pathologist, radiologist, and thoracic surgeon. Non-small cell lung cancer specimens are tested for various mutations, which, if present, can be treated with new targeted molecular therapies. The family physician should remain involved in the patient's care to ensure that the values and wishes of the patient and family are considered and, if necessary, to coordinate end-of-life care. Early palliative care improves quality of life and may prolong survival. Family physicians should concentrate on early recognition of lung cancer, as well as prevention by encouraging tobacco cessation at every visit. The U.S. Preventive Services Task Force recommends lung cancer screening using low-dose computed tomography in high-risk patients. However, the American Academy of Family Physicians concludes that the evidence is insufficient to recommend for or against screening. Whether to screen high-risk patients should be a shared decision between the physician and patient.

Clearance of chlamydial elementary bodies from the conjunctival sac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, H.R.; Velez, V.L.

1987-07-01

The rate of disappearance of inactivated Chlamydia trachomatis elementary body (EB) preparations from the conjunctival sac was studied in monkeys. Direct fluorescent antibody (DFA) cytology showed that the majority of EB had been cleared from the eye within 24 hr of the inoculation of 1 X 10(6) inactivated EB, although small numbers of EB could be detected for up to 144 hr. The rate of clearance in normal and ocular immune animals did not differ, and formalin-killed and UV-inactivated EBs disappeared at a comparable rate. These studies suggest that chlamydial EB are cleared relatively quickly from the eye and supportmore » the notion that EBs detected by DFA cytology indicate the presence of current infection.« less

Cleavage of the NF-κB Family Protein p65/RelA by the Chlamydial Protease-like Activity Factor (CPAF) Impairs Proinflammatory Signaling in Cells Infected with Chlamydiae*

PubMed Central

Christian, Jan; Vier, Juliane; Paschen, Stefan A.; Häcker, Georg

2010-01-01

Chlamydiae are obligate intracellular bacteria that frequently cause human disease. Chlamydiae replicate in a membranous vacuole in the cytoplasm termed inclusion but have the ability to transport proteins into the host cell cytosol. Chlamydial replication is associated with numerous changes of host cell functions, and these changes are often linked to proteolytic events. It has been shown earlier that the member of the NF-κB family of inflammation-associated transcription factors, p65/RelA, is cleaved during chlamydial infection, and a chlamydial protease has been implicated. We here provide evidence that the chlamydial protease chlamydial protease-like activity factor (CPAF) is responsible for degradation of p65/RelA during infection. This degradation was seen in human and in mouse cells infected with either Chlamydia trachomatis or Chlamydia pneumoniae where it correlated with the expression of CPAF and CPAF activity. Isolated expression of active C. trachomatis or C. pneumoniae CPAF in human or mouse cells yielded a p65 fragment of indistinguishable size from the one generated during infection. Expression of active CPAF in human cells caused a mild reduction in IκBα phosphorylation but a strong reduction in NF-κB reporter activity in response to interleukin-1β. Infection with C. trachomatis likewise reduced this responsiveness. IL-1β-dependent secretion of IL-8 was further reduced by CPAF expression. Secretion of CPAF is, thus, a mechanism that reduces host cell sensitivity to a proinflammatory stimulus, which may facilitate bacterial growth in vivo. PMID:21041296

Increased proximal acid reflux is associated with early readmission following lung transplantation.

PubMed

Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2016-02-01

Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed. This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring. Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis. Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered. © 2015 John Wiley & Sons Ltd.

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2014-09-01

Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W...CONTRACT NUMBER Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer 5b. GRANT NUMBER W81XWH-12-1-0236 5c...NOTES 14. ABSTRACT Purpose and scope: Stereotactic ablative radiotherapy ( SABR ) has become a new standard of care for early stage lung

Comparing end-of-life care for hospitalized patients with chronic obstructive pulmonary disease and lung cancer in Taiwan.

PubMed

Chou, Wen-Chi; Lai, Yu-Te; Huang, Yun-Chin; Chang, Chen-Ling; Wu, Wei-Shan; Hung, Yu-Shin

2013-01-01

When it comes to end-of-life care, chronic obstructive pulmonary disease (COPD) patients are often treated differently from lung cancer patients. However, few reports have compared end-of-life care between these two groups. We investigated the differences between patients with end-stage COPD and end-stage lung cancer based on end-of-life symptoms and clinical practice patterns using a retrospective study of COPD and lung cancer patients who died in an acute care hospital in Taiwan. End-stage COPD patients had more comorbidities and spent more days in the intensive care unit (ICU) than end-stage lung cancer patients. They were more likely to die in the ICU and less likely to receive hospice care. COPD patients also had more invasive procedures, were less likely to use narcotic and sedative drugs, and were less likely to have given do-not-resuscitate consent. Symptoms were similar between these two groups. Differences in treatment management suggest that COPD patients receive more care aimed at prolonging life than care aimed at relieving symptoms and providing end-of-life support. It may be more difficult to determine when COPD patients are at the end-of-life stage than it is to identify when lung cancer patients are at that stage. Our findings indicate that in Taiwan, more effort should be made to give end-stage COPD patients the same access to hospice care as end-stage lung cancer patients.

Raw milk consumption and other early-life farm exposures and adult pulmonary function in the Agricultural Lung Health Study.

PubMed

Wyss, Annah B; House, John S; Hoppin, Jane A; Richards, Marie; Hankinson, John L; Long, Stuart; Henneberger, Paul K; Beane Freeman, Laura E; Sandler, Dale P; O'Connell, Elizabeth Long; Cummings, Christie Barker; Umbach, David M; London, Stephanie J

2018-03-01

Literature suggests that early exposure to the farming environment protects against atopy and asthma; few studies have examined pulmonary function. We evaluated associations between early-life farming exposures and pulmonary function in 3061 adults (mean age=63) from a US farming population using linear regression. Childhood raw milk consumption was associated with higher FEV 1 (β=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (β=66.2 mL, 95% CI 13.2 to 119.1 mL, p=0.01). We did not find appreciable associations with other early-life farming exposures. We report a novel association between raw milk consumption and higher pulmonary function that lasts into older adulthood. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Estimation of lung cancer burden in Australia, the Philippines, and Singapore: an evaluation of disability adjusted life years.

PubMed

Morampudi, Suman; Das, Neha; Gowda, Arun; Patil, Anand

2017-02-01

Lung cancer is one of the leading cancers and major causes of cancer mortality worldwide. The economic burden associated with the high mortality of lung cancer is high, which accounts for nearly $180 billion on a global scale in 2008. This paper aims to understand the economic burden of lung cancer in terms of disability adjusted life years (DALY) in Australia, the Philippines, and Singapore. The years of life lost (YLL) and years lost due to disability (YLD) were calculated using the formula developed by Murray and Lopez in 1996 as part of a comprehensive assessment of mortality and disability for diseases, injuries and risk factors in 1990 and projected to 2020. The same formula is represented in the Global Burden of Disease template provided by the World Health Organization. Appropriate assumptions were made when data were unavailable and projections were performed using regression analysis to obtain data for 2015. The total DALYs due to lung cancer in Australia, the Philippines, and Singapore were 91,695, 38,584, and 12,435, respectively, and the corresponding DALY rates per a population of 1,000 were 4.0, 0.4, and 2.2, respectively, with a discount rate of 3%. When researchers calculated DALYs without the discount rate, the burden of disease increased substantially; the DALYs were 117,438 in Australia, 50,977 in the Philippines, and 16,379 in Singapore. Overall, YLL or premature death accounted for more than 95% of DALYs in these countries. Strategies for prevention, early diagnosis, and prompt treatment must be devised for diseases where the major burden is due to mortality.

Estimation of lung cancer burden in Australia, the Philippines, and Singapore: an evaluation of disability adjusted life years

PubMed Central

Morampudi, Suman; Das, Neha; Gowda, Arun; Patil, Anand

2017-01-01

Objective: Lung cancer is one of the leading cancers and major causes of cancer mortality worldwide. The economic burden associated with the high mortality of lung cancer is high, which accounts for nearly $180 billion on a global scale in 2008. This paper aims to understand the economic burden of lung cancer in terms of disability adjusted life years (DALY) in Australia, the Philippines, and Singapore. Methods: The years of life lost (YLL) and years lost due to disability (YLD) were calculated using the formula developed by Murray and Lopez in 1996 as part of a comprehensive assessment of mortality and disability for diseases, injuries and risk factors in 1990 and projected to 2020. The same formula is represented in the Global Burden of Disease template provided by the World Health Organization. Appropriate assumptions were made when data were unavailable and projections were performed using regression analysis to obtain data for 2015. Results: The total DALYs due to lung cancer in Australia, the Philippines, and Singapore were 91,695, 38,584, and 12,435, respectively, and the corresponding DALY rates per a population of 1,000 were 4.0, 0.4, and 2.2, respectively, with a discount rate of 3%. When researchers calculated DALYs without the discount rate, the burden of disease increased substantially; the DALYs were 117,438 in Australia, 50,977 in the Philippines, and 16,379 in Singapore. Overall, YLL or premature death accounted for more than 95% of DALYs in these countries. Conclusions: Strategies for prevention, early diagnosis, and prompt treatment must be devised for diseases where the major burden is due to mortality. PMID:28443206

Evidence establishing a link between prenatal and early-life stress and asthma development.

PubMed

Rosa, Maria José; Lee, Alison G; Wright, Rosalind J

2018-04-01

The objective of this review is to provide an update on our evolving understanding of the effects of stress in pregnancy and during early development on the onset of asthma-related phenotypes across childhood, adolescence, and into early adulthood. Accumulating evidence over the past 2 decades has established that prenatal and early-life psychological stress and stress correlates (e.g., maternal anxiety or depression) increase the risk for childhood respiratory disorders. Recent systematic reviews and meta-analyses including numerous prospective epidemiological and case-control studies substantiate a significant effect of prenatal stress and stress in early childhood on the development of wheeze, asthma, and other atopic-related disorders (eczema and allergic rhinitis), with many studies showing an exposure-response relationship. Offspring of both sexes are susceptible to perinatal stress, but effects differ. The impact of stress on child wheeze/asthma can also be modified by exposure timing. Moreover, coexposure to prenatal stress can enhance the effect of chemical stressors, such as prenatal traffic-related air pollution, on childhood respiratory disease risk. Understanding complex interactions among exposure dose, timing, child sex, and concurrent environmental exposures promises to more fully characterize stress effects and identify susceptible subgroups. Although the link between perinatal stress and childhood asthma-related phenotypes is now well established, pathways by which stress predisposes children to chronic respiratory disorders are not as well delineated. Mechanisms central to the pathophysiology of wheeze/asthma and lung growth and development overlap and involve a cascade of events that include disrupted immune, neuroendocrine, and autonomic function as well as oxidative stress. Altered homeostatic functioning of these integrated systems during development can enhance vulnerability to asthma and altered lung development. Mechanistic studies that

Productivity losses attributable to untreated chlamydial infection and associated pelvic inflammatory disease in reproductive-aged women.

PubMed

Blandford, John M; Gift, Thomas L

2006-10-01

The productivity losses attributable to disease-related morbidity and mortality impose a burden on society in general and on employers in particular. A reliable assessment of the productivity losses associated with untreated infection with Chlamydia trachomatis (Ct) would complement earlier work on direct medical costs and contribute to an estimate of the full cost of chlamydial disease. The goal of this study was to estimate the discounted lifetime productivity losses attributable to untreated chlamydial infection in reproductive-aged women. We developed a cost model using Monte Carlo methods to estimate the lifetime discounted productivity losses attributable to untreated lower genital tract Ct infection among reproductive-aged women. The model considered the impact of disability resulting from acute pelvic inflammatory disease (PID) associated with untreated Ct infection and from the sequelae of acute PID, including chronic pelvic pain, ectopic pregnancy, and infertility. To accommodate disparate Ct infection rates and labor market characteristics across age groups, we matched age-based risk factors for Ct infection with labor market patterns. Data sources included the 2001 National Chlamydia Surveillance Data, the 2001 Current Population Survey, and published literature. Estimates indicate that the mean weighted productivity losses per untreated Ct infection were approximately US dollars 130 (in year 2001 dollars). Mean weighted productivity losses per case of acute PID were estimated at US dollars 649. Estimated productivity losses were highly correlated with age, reflecting age-dependent differences in labor market characteristics. The productivity losses attributable to untreated infection with Ct and to sequelae of this infection form a substantial portion of the total economic burden of disease. Effective programs to prevent chlamydial infection and effective screening, diagnosis, and treatment of Ct-infected women may reduce productivity losses and

The influence of living conditions in early life on life satisfaction in old age.

PubMed

Deindl, Christian

2013-03-01

This article examines the influence of living conditions in early life on life satisfaction in old age in eleven Western European countries. It combines the influence of individual conditions, for example housing and family background, with country characteristics in the decade of birth. Using pooled data from the second and third wave of the Survey of Health, Ageing and Retirement in Europe, multilevel models show that early life living conditions have an influence on life satisfaction in old age. Furthermore, interaction effects between current and past living conditions show that adverse living conditions strengthen the effect of early life on life satisfaction in later life and therefore are an indication of cumulative inequality over the life course. Copyright © 2012 Elsevier Ltd. All rights reserved.

Therapeutic approach to respiratory infections in lung transplantation.

PubMed

Clajus, Carolina; Blasi, Francesco; Welte, Tobias; Greer, Mark; Fuehner, Thomas; Mantero, Marco

2015-06-01

Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultrashort Echo-Time Magnetic Resonance Imaging Is a Sensitive Method for the Evaluation of Early Cystic Fibrosis Lung Disease

PubMed Central

Roach, David J.; Crémillieux, Yannick; Fleck, Robert J.; Brody, Alan S.; Serai, Suraj D.; Szczesniak, Rhonda D.; Kerlakian, Stephanie; Clancy, John P.

2016-01-01

Rationale: Recent advancements that have been made in magnetic resonance imaging (MRI) improve our ability to assess pulmonary structure and function in patients with cystic fibrosis (CF). A nonionizing imaging modality that can be used as a serial monitoring tool throughout life can positively affect patient care and outcomes. Objectives: To compare an ultrashort echo-time MRI method with computed tomography (CT) as a biomarker of lung structure abnormalities in young children with early CF lung disease. Methods: Eleven patients with CF (mean age, 31.8 ± 5.7 mo; median age, 33 mo; 7 male and 4 female) were imaged via CT and ultrashort echo-time MRI. Eleven healthy age-matched patients (mean age, 22.5 ± 10.2 mo; median age, 23 mo; 5 male and 6 female) were imaged via ultrashort echo-time MRI. CT scans of 13 additional patients obtained for clinical indications not affecting the heart or lungs and interpreted as normal provided a CT control group (mean age, 24.1 ± 11.7 mo; median age, 24 mo; 6 male and 7 female). Studies were scored by two experienced radiologists using a well-validated CF-specific scoring system for CF lung disease. Measurements and Main Results: Correlations between CT and ultrashort echo-time MRI scores of patients with CF were very strong, with P values ≤0.001 for bronchiectasis (r = 0.96) and overall score (r = 0.90), and moderately strong for bronchial wall thickening (r = 0.62, P = 0.043). MRI easily differentiated CF and control groups via a reader CF-specific scoring system. Conclusions: Ultrashort echo-time MRI detected structural lung disease in very young patients with CF and provided imaging data that correlated well with CT. By quantifying early CF lung disease without using ionizing radiation, ultrashort echo-time MRI appears well suited for pediatric patients requiring longitudinal imaging for clinical care or research studies. Clinical Trial registered with www.clinicaltrials.gov (NCT01832519). PMID

[Lung transplantation.].

PubMed

Guðmundsson, G

2000-09-01

Lung transplantation is an option in the treatment of end stage lung diseases, excluding lung cancer, that lead to short life expectancy and poor quality of life. Now they are mostly limited by shortage of donor organs and longterm complications. They are used for various lung diseases such as pulmonary vascular diseases, fibrosing diseases, chronic obstructive pulmonary diseases and diseases that cause chronic infections. Depending on the indication it is possible to perform heart and lung transplantation, single lung or double lung transplantation.Indications, contraindications, surgical methods, immunosuppression, complications and outcomes will be discussed. Survival is not as good as for other solid organ transplantation. Measurement of pulmonary function and quality of life improve with lung transplantation. Bronchiolitis obliterans is the most common complication and is the most limiting factor. A few Icelanders have undergone lung transplantation, most of them in Gothenburg, Sweden. The future of lung transplantation depends on limiting the incidence of bronchiolitis obliterans and finding more organ donors.

Early Life Stress, Mood, and Anxiety Disorders.

PubMed

Syed, Shariful A; Nemeroff, Charles B

2017-02-01

Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health's proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

Identification of a three-miRNA signature as a blood-borne diagnostic marker for early diagnosis of lung adenocarcinoma

PubMed Central

Gao, Xujie; Wei, Feng; Zhang, Xinwei; Su, Yanjun; Wang, Changli; Li, Hui; Ren, Xiubao

2016-01-01

Background The subtypes of NSCLC have unique characteristics of pathogenic mechanism and responses to targeted therapies. Thus, non-invasive markers for diagnosis of different subtypes of NSCLC at early stage are needed. Results Based on the results from the screening and validation process, 3 miRNAs (miR-532, miR-628-3p and miR-425-3p) were found to display significantly different expression levels in early-stage lung adenocarcinoma, as compared to those in healthy controls. ROC analysis showed that the miRNA–based biomarker could distinguish lung adenocarcinoma from healthy controls with high AUC (0.974), sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs could also distinguish lung adenocarcinoma from lung benigh diseases and other subtypes of lung cancer. Methods Two hundreds and one early-stage lung adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy controls were recruited to this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. A risk score model was established to evaluate the diagnostic value of the plasma miRNA profiling system. Conclusions Taken together, these findings suggest that the 3 miRNA–based biomarker might serve as a novel non-invasive approach for diagnosis of early-stage lung adenocarcinoma. PMID:27036025

“Sentinel” Circulating Tumor Cells Allow Early Diagnosis of Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Ilie, Marius; Hofman, Véronique; Long-Mira, Elodie; Selva, Eric; Vignaud, Jean-Michel; Padovani, Bernard; Mouroux, Jérôme; Marquette, Charles-Hugo; Hofman, Paul

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. Migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis. We aimed to examine the presence of CTCs in complement to CT-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis. The presence of CTCs was examined by an ISET filtration-enrichment technique, for 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), including 42 control smokers and 35 non-smoking healthy individuals. CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers. COPD patients were monitored annually by low-dose spiral CT. CTCs were detected in 3% of COPD patients (5 out of 168 patients). The annual surveillance of the CTC-positive COPD patients by CT-scan screening detected lung nodules 1 to 4 years after CTC detection, leading to prompt surgical resection and histopathological diagnosis of early-stage lung cancer. Follow-up of the 5 patients by CT-scan and ISET 12 month after surgery showed no tumor recurrence. CTCs detected in COPD patients had a heterogeneous expression of epithelial and mesenchymal markers, which was similar to the corresponding lung tumor phenotype. No CTCs were detected in control smoking and non-smoking healthy individuals. CTCs can be detected in patients with COPD without clinically detectable lung cancer. Monitoring “sentinel” CTC-positive COPD patients may allow early diagnosis of lung cancer. PMID:25360587

Osteoporosis in survivors of early life starvation.

PubMed

Weisz, George M; Albury, William R

2013-01-01

The objective of this study was to provide evidence for the association of early life nutritional deprivation and adult osteoporosis, in order to suggest that a history of such deprivation may be an indicator of increased risk of osteoporosis in later life. The 'fetal programming' of a range of metabolic and cardiovascular disorders in adults was first proposed in the 1990s and more recently extended to disorders of bone metabolism. Localised famines during World War II left populations in whom the long-term effects of maternal, fetal and infantile nutritional deprivation were studied. These studies supported the original concept of 'fetal programming' but did not consider bone metabolism. The present paper offers clinical data from another cohort of World War II famine survivors - those from the Holocaust. The data presented here, specifically addressing the issue of osteoporosis, report on 11 Holocaust survivors in Australia (five females, six males) who were exposed to starvation in early life. The cases show, in addition to other metabolic disorders associated with early life starvation, various levels of osteoporosis, often with premature onset. The cohort studied is too small to support firm conclusions, but the evidence suggests that the risk of adult osteoporosis in both males and females is increased by severe starvation early in life - not just in the period from gestation to infancy but also in childhood and young adulthood. It is recommended that epidemiological research on this issue be undertaken, to assist planning for the future health needs of immigrants to Australia coming from famine affected backgrounds. Pending such research, it would be prudent for primary care health workers to be alert to the prima facie association between early life starvation and adult osteoporosis, and to take this factor into account along with other indicators when assessing a patient's risk of osteoporosis in later life.

Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list.

PubMed

Higo, Hisao; Kurosaki, Takeshi; Ichihara, Eiki; Kubo, Toshio; Miyoshi, Kentaroh; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyahara, Nobuaki; Kiura, Katsuyuki; Miyoshi, Shinichiro; Oto, Takahiro

2017-07-01

Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and

Low-grade disease activity in early life precedes childhood asthma and allergy.

PubMed

Chawes, Bo Lund Krogsgaard

2016-08-01

Asthma and allergies are today the most common chronic diseases in children and the leading causes of school absences, chronic medication usage, emergency department visits and hospitalizations, which affect all members of the family and represent a significant societal and scientific challenge. These highly prevalent disorders are thought to originate from immune distortion in early childhood, but the etiology and heterogeneity of the disease mechanisms are not understood, which hampers preventive initiatives and makes treatment inadequate. The objective of this thesis is to investigate the presence of an early life disease activity prior to clinical symptoms to understand the anteceding pathophysiological steps towards childhood asthma and allergy. The thesis is built on seven studies from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) birth cohort examining biomarkers of disease activity in 411 asymptomatic neonates in cord blood (I-II), urine (III), exhaled breath (IV-V) and infant lung function (VI-VII) in relation to the subsequent development of asthma and allergy during the first seven years of life. In papers I-II, we studied cord blood chemokines and 25(OH)-vitamin D, which represent a proxy of the inborn immature immune system, the intrauterine milieu, and the maternal immune health during pregnancy. High levels of the Th2-related chemokine CCL22 and high CCL22/CXCL11 ratio were positively correlated with total IgE level during preschool age (II). This suggests an inborn Th2 skewing of the immune system in healthy newborns subsequently developing elevated total IgE antibodies, which is considered to increase the risk of asthma and allergies later in life. Additionally, deficient cord blood 25(OH)-vitamin D levels were associated with a 2.7-fold increased risk of recurrent wheeze at age 0-7 years (I). Together, these findings support the concept that early life immune programming in the pre-symptomatic era plays an essential role

Chlamydial infection among patients attending STD and genitourinary clinics in Taiwan

PubMed Central

Chen, Kow-Tong; Chen, Shou-Chien; Chiang, Chien-Chou; Li, Lan-Hui; Tang, Li-Hui

2007-01-01

Background The main objective of this study is to examine the epidemiology of Chlamydia trachomatis (CT) infection amongst patients (473 men, 180 women) seen two hospitals in Taiwan. Methods Between July 2004 and June 2005, a total of 653 patients provided first-void urine samples for examination of CT using PCR assay. Results The overall prevalence of CT infection was 18.4% (95% confidence interval [CI] 17.3–19.5). Prevalence for men and women were 16.7 % (95% CI 15.3–18.0%) and 22.8% (95% CI 17.5–28.1%), respectively. Age group-specific prevalence was 25.7% (95% CI 22.5–28.9%) in < 20 year olds, 23.5% (95% CI 20.3–26.7%) in 20–24 year olds, 22.3% (95% CI 18.9–25.7%) in 25–30 year olds, and 11.5% (95% CI 10.3–12.7%) in > 30 year olds. Independent risk factors for chlamydial infection included younger age (aged ≤ 30 years) (adjusted odds ratio [AOR] = 2.44; 95% CI 1.52–3.84; p < 0.001), inconsistent condom use (AOR = 2.01; 95% CI 1.32–3.06; p < 0.001), being symptomatic (dysuria, urethral discharge) at the time of testing (AOR = 1.84; 95% CI 1.21–2.80; p < 0.001), and having N. gonorrhoeae infection (AOR = 3.82; 95% CI 2.20–6.58; p < 0.001). Conclusion Genital chlamydial infection is an important sexually transmitted disease in Taiwan. Young Taiwanese persons attending a STD clinic should be screened for CT infection and counselled on condom use. PMID:17593300

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2017-11-01

SABR) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W Loo Jr, MD PhD CONTRACTING ORGANIZATION: The Leland Stanford Junior University...Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Billy W Loo Jr, MD...for early stage lung cancer in patients who are not candidates for surgery because of excessive surgical risk, and will be an important treatment option

Embryonic essential myosin light chain regulates fetal lung development in rats.

PubMed

Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge

2007-09-01

Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate

PubMed Central

Terrin, Gianluca; Berni Canani, Roberto; Di Chiara, Maria; Pietravalle, Andrea; Aleandri, Vincenzo; Conte, Francesca; De Curtis, Mario

2015-01-01

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated. PMID:26690476

Donor age and early graft failure after lung transplantation: a cohort study.

PubMed

Baldwin, M R; Peterson, E R; Easthausen, I; Quintanilla, I; Colago, E; Sonett, J R; D'Ovidio, F; Costa, J; Diamond, J M; Christie, J D; Arcasoy, S M; Lederer, D J

2013-10-01

Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1-year graft failure and primary graft dysfunction (PGD). The rate of 1-year graft failure was similar among recipients of lungs from donors age 18-64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56-64 years had increased rates of 1-year graft failure (p-values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1-year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01-1.50 and adjusted HR 2.15, 95% CI 1.47-3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chronic Hypoxia Accentuates Dysanaptic Lung Growth.

PubMed

Llapur, Conrado J; Martínez, Myriam R; Grassino, Pedro T; Stok, Ana; Altieri, Héctor H; Bonilla, Federico; Caram, María M; Krowchuk, Natasha M; Kirby, Miranda; Coxson, Harvey O; Tepper, Robert S

2016-08-01

Adults born and raised at high altitudes have larger lung volumes and greater pulmonary diffusion capacity compared with adults at low altitude; however, it remains unclear whether the air and tissue volumes have comparable increases and whether there is a difference in airway size. To assess the effect of chronic hypoxia on lung growth using in vivo high-resolution computed tomography measurements. Healthy adults born and raised at moderate altitude (2,000 m above sea level; n = 19) and at low altitude (400 m above sea level; n = 23) underwent high-resolution computed tomography. Differences in total lung, air, and tissue volume, mean lung density, as well as airway lumen and wall areas in anatomically matched airways were compared between groups. No significant differences for age, sex, weight, or height were found between the two groups (P > 0.05). In a multivariate regression model, altitude was a significant contributor for total lung volume (P = 0.02), air volume (P = 0.03), and tissue volume (P = 0.03), whereby the volumes were greater for the moderate- versus the low-altitude group. However, altitude was not a significant contributor for mean lung density (P = 0.35) or lumen and wall areas in anatomically matched segmental, subsegmental, and subsubsegmental airways. Our findings suggest that the adult lung did not increase lung volume later in life by expansion of an existing number of alveoli, but rather from increased alveolarization early in life. In addition, chronic hypoxia accentuates dysanaptic lung growth by increasing the lung parenchyma but not the airways.

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

The acceptance of illness, the intensity of pain and the quality of life in patients with lung cancer

PubMed Central

Polański, Jacek; Jankowska-Polanska, Beata; Lomper, Katarzyna; Janczak, Dariusz; Rosinczuk, Joanna

2017-01-01

Background Lung cancer is the major cause of cancer related deaths worldwide. The overall 5-year survival rate is very low and accounts for only 15%. Poor quality of life is considered a prognostic factor for shorter survival in lung cancer patients. The aim of the study was to examine the relationships between pain, the acceptance of illness and quality of life in patients with lung cancer. Methods The study included 155 patients with lung cancer with mean age of 62.23 [standard deviation (SD)=9.86] years. We used the Acceptance of Illness Scale (AIS) and the Visual Analog Scale (VAS) for pain, and the Short Form Health Survey (SF-8) for the assessment of quality of life. For statistical analysis, Spearman’s rank correlation coefficient and linear regression method were used. Results Mean score of the acceptance of illness was 27.1 (SD=9.2). Mean score of the pain severity as measured by the VAS was 4.07 (SD=1.83). The acceptance of illness was significantly positively correlated with all the domains of quality of life. Both the AIS and the VAS were independent determinants of physical and mental components of quality of life. Age and World Health Organization (WHO) performance status were additional predictors of physical component of quality of life. Conclusions The knowledge about the acceptance of illness, consequences of the decreased acceptance of illness, and factors affecting its level in patients with lung cancer is still insufficient. Relationships among acceptance of illness, quality of life, and pain should be further investigated. PMID:29221267

The acceptance of illness, the intensity of pain and the quality of life in patients with lung cancer.

PubMed

Chabowski, Mariusz; Polański, Jacek; Jankowska-Polanska, Beata; Lomper, Katarzyna; Janczak, Dariusz; Rosinczuk, Joanna

2017-09-01

Lung cancer is the major cause of cancer related deaths worldwide. The overall 5-year survival rate is very low and accounts for only 15%. Poor quality of life is considered a prognostic factor for shorter survival in lung cancer patients. The aim of the study was to examine the relationships between pain, the acceptance of illness and quality of life in patients with lung cancer. The study included 155 patients with lung cancer with mean age of 62.23 [standard deviation (SD)=9.86] years. We used the Acceptance of Illness Scale (AIS) and the Visual Analog Scale (VAS) for pain, and the Short Form Health Survey (SF-8) for the assessment of quality of life. For statistical analysis, Spearman's rank correlation coefficient and linear regression method were used. Mean score of the acceptance of illness was 27.1 (SD=9.2). Mean score of the pain severity as measured by the VAS was 4.07 (SD=1.83). The acceptance of illness was significantly positively correlated with all the domains of quality of life. Both the AIS and the VAS were independent determinants of physical and mental components of quality of life. Age and World Health Organization (WHO) performance status were additional predictors of physical component of quality of life. The knowledge about the acceptance of illness, consequences of the decreased acceptance of illness, and factors affecting its level in patients with lung cancer is still insufficient. Relationships among acceptance of illness, quality of life, and pain should be further investigated.

The diagnostic value of narrow-band imaging for early and invasive lung cancer: a meta-analysis.

PubMed

Zhu, Juanjuan; Li, Wei; Zhou, Jihong; Chen, Yuqing; Zhao, Chenling; Zhang, Ting; Peng, Wenjia; Wang, Xiaojing

2017-07-01

This study aimed to compare the ability of narrow-band imaging to detect early and invasive lung cancer with that of conventional pathological analysis and white-light bronchoscopy. We searched the PubMed, EMBASE, Sinomed, and China National Knowledge Infrastructure databases for relevant studies. Meta-disc software was used to perform data analysis, meta-regression analysis, sensitivity analysis, and heterogeneity testing, and STATA software was used to determine if publication bias was present, as well as to calculate the relative risks for the sensitivity and specificity of narrow-band imaging vs those of white-light bronchoscopy for the detection of early and invasive lung cancer. A random-effects model was used to assess the diagnostic efficacy of the above modalities in cases in which a high degree of between-study heterogeneity was noted with respect to their diagnostic efficacies. The database search identified six studies including 578 patients. The pooled sensitivity and specificity of narrow-band imaging were 86% (95% confidence interval: 83-88%) and 81% (95% confidence interval: 77-84%), respectively, and the pooled sensitivity and specificity of white-light bronchoscopy were 70% (95% confidence interval: 66-74%) and 66% (95% confidence interval: 62-70%), respectively. The pooled relative risks for the sensitivity and specificity of narrow-band imaging vs the sensitivity and specificity of white-light bronchoscopy for the detection of early and invasive lung cancer were 1.33 (95% confidence interval: 1.07-1.67) and 1.09 (95% confidence interval: 0.84-1.42), respectively, and sensitivity analysis showed that narrow-band imaging exhibited good diagnostic efficacy with respect to detecting early and invasive lung cancer and that the results of the study were stable. Narrow-band imaging was superior to white light bronchoscopy with respect to detecting early and invasive lung cancer; however, the specificities of the two modalities did not differ

Improvement in health-related quality of life after lung transplantation

PubMed Central

Santana, Maria-Jose; Feeny, David; Jackson, Katherine; Weinkauf, Justin; Lien, Dale

2009-01-01

BACKGROUND/OBJECTIVE: Traditional survival outcomes do not reflect the effects on the health-related quality of life (HRQL) of patients. HRQL following lung transplantation has not been studied systematically. The Health Utilities Index (HUI) is a family (HUI2 and HUI3) of measures of HRQL that has not been previously used to assess HRQL in lung transplantation. The objective of the present study was to assess the impact of lung transplantation on patient’s HRQL using the HUI. METHODS: A total of 43 patients completed a battery of questionnaires before lung transplantation, and at three months and six months after lung transplantation. The 15-item questionnaire (HUI2 and HUI3) was used. Overall scores were based on a conventional scale (0.00 = dead, 1.00 = perfect health). Mental health was assessed by the Hospital Anxiety and Depression Scale. Adherence to medication and exercise were assessed by Morisky’s and Godin’s questionnaires, respectively. RESULTS: Sixty-five per cent of the patients were men, with a mean age of 53 years (range 18 to 67 years). The mean overall HUI3 score for the lung transplant candidates (0.57) was much lower than for the lung transplant recipients (0.82) at six months post-transplantation. This difference was clinically important and statistically significant (P<0.05 [paired ttest, degrees of freedom (df) = 35]). Differences in mean Hospital Anxiety and Depression Scale scores after transplantation were statistically significant (P<0.05 [paired t test, df=35]). After six months, transplant recipients were more adherent to medication (P<0.05 [χ2 test, df=1]). Recipients were able to increase the duration of exercise at all levels of intensity. CONCLUSION: Lung transplantation improved the patients’ HRQL and adherence to medication. Anxiety levels persisted six months after transplantation but depression levels had decreased significantly. PMID:19851533

Metabotyping Patients’ Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery

PubMed Central

Maltesen, Raluca Georgiana; Rasmussen, Bodil Steen; Pedersen, Shona; Hanifa, Munsoor Ali; Kucheryavskiy, Sergey; Kristensen, Søren Risom; Wimmer, Reinhard

2017-01-01

Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood samples were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression. PMID:28074924

Antibody responses to the chlamydial heat shock proteins hsp60 and hsp70 are H-2 linked.

PubMed Central

Zhong, G; Brunham, R C

1992-01-01

The effects of both H-2 and non-H-2 genes on antibody responses to two Chlamydia trachomatis heat shock proteins (hsp60 and hsp70) were investigated. These chlamydial proteins are homologs of Escherichia coli GroEL (hsp60) and DnaK (hsp70) and are highly sequence conserved between bacterial and mammalian sources. Antibody responses among 17 different strains of mice immunized with C. trachomatis serovar B and serovar C elementary bodies were evaluated by immunoblot, radioimmunoprecipitation and enzyme-linked immunosorbent assay. Antibody responses to the two proteins displayed host genetic restriction. Of six distinctive H-2 haplotypes, only H-2d generated high antibody responses to hsp70. Five of the six H-2 haplotypes, i.e., H-2a, H-2d, H-2k, H-2q, and H-2s, produced high antibody responses to hsp60. Only the H-2b-bearing strain had low antibody responses to hsp60. By using congenic and H-2 recombinant strains, the genes responsible for regulating antibody responses to hsp70 and hsp60 were mapped to the K-IA region of the H-2 locus. In F1 hybrid crosses between high and low responders, high responses to hsp60 and hsp70 were dominant traits. Other genes outside the H-2 locus also influenced antibody responses to hsp60 and hsp70, since inbred strains of identical H-2 but different background genes displayed variable antibody responses to the proteins. The genetic control of murine immune responses to C. trachomatis hsp60, a putative chlamydial immunopathologic antigen, suggests that a similar genetic mechanism may also exist in humans, and this observation may help to explain the observed variability in the spectrum of chlamydial diseases seen in humans. Images PMID:1639484

Broncho-esophageal fistula leading to lung abscess: A life-threatening emergency detected on FDG PET/CT in a case of carcinoma of middle third esophagus.

PubMed

Puranik, Ameya D; Purandare, Nilendu C; Agrawal, Archi; Shah, Sneha; Rangarajan, Venkatesh

2013-07-01

Sinister undesirable pathologies often accompany malignancies. Though the entire emphasis is on cancer management, these benign conditions are more life-threatening than the primary malignancy itself. We report an interesting imaging finding of broncho-esophageal fistula leading to lung abscess on (18)F- fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG PET/CT) in large middle esophageal cancer, which due to early detection, was promptly managed.

Early-Life Socioeconomic Status and Adult Physiological Functioning: A Life Course Examination of Biosocial Mechanisms.

PubMed

Yang, Yang Claire; Gerken, Karen; Schorpp, Kristen; Boen, Courtney; Harris, Kathleen Mullan

2017-01-01

A growing literature has demonstrated a link between early-life socioeconomic conditions and adult health at a singular point in life. No research exists, however, that specifies the life course patterns of socioeconomic status (SES) in relation to the underlying biological processes that determine health. Using an innovative life course research design consisting of four nationally representative longitudinal datasets that collectively cover the human life span from early adolescence to old age (Add Health, MIDUS, NSHAP, and HRS), we address this scientific gap and assess how SES pathways from childhood into adulthood are associated with biophysiological outcomes in different adult life stages. For each dataset, we constructed standardized composite measures of early-life SES and adult SES and harmonized biophysiological measurements of immune and metabolic functioning. We found that the relative importance of early-life SES and adult SES varied across young, mid, and late adulthood, such that early-life SES sets a life course trajectory of socioeconomic well-being and operates through adult SES to influence health as adults age. We also documented evidence of the detrimental health effects of downward mobility and persistent socioeconomic disadvantage. These findings are the first to specify the life course patterns of SES that matter for underlying biophysiological functioning in different stages of adulthood. The study thus contributes new knowledge critical for improving population health by identifying the particular points in the life course at which interventions might be most effective in preventing disease and premature mortality.

Factors influencing the psychology and quality of life in lung cancer patients.

PubMed

Wang, Bin; Hao, Nan; Zhang, Xun

2017-09-01

To determine the factors closely correlated with the unhealthy psychological status of patients with lung cancer and to ascertain whether the unhealthy psychology adversely affects their quality-of-life (QOL). Methods: Patients newly diagnosed with lung cancer between May 2013 and December 2015 in the Department of Thoracic Surgery, Tianjin 4th Centre Hospital, Tianjin, China were enrolled in this cross-sectional study. Patients were asked to complete the Symptom Checklist 90 (SCL-90) and Quality of Life Questionnaire (QLQ-C30) survey. From the responses, the correlation between the patient's psychological status and QOL were analyzed with respect to several variables. Results: From the total of 258 patients subjected to the test, 168 belonged to the unhealthy psychology group and 90 to the healthy psychology group. Multiple regression analysis revealed that significant factors related to poor QOL among the 2 groups are gender (p=0.02), younger age (p=0.001), surgical history (p=0.04), employment status (p=0.03), and medical insurance (p=0.01) significantly predicted the severity of unhealthy psychology in lung cancer patients. A significantly negative correlation was noted between the points of SCL-90 and the general QOL in all included patients (p=0.03). Conclusion: Gender, younger age, surgical history, employment status, and medical insurance significantly predicted the severity of unhealthy psychology in lung cancer patients.

Factors influencing the psychology and quality of life in lung cancer patients

PubMed Central

Wang, Bin; Hao, Nan; Zhang, Xun

2017-01-01

Objectives: To determine the factors closely correlated with the unhealthy psychological status of patients with lung cancer and to ascertain whether the unhealthy psychology adversely affects their quality-of-life (QOL). Methods: Patients newly diagnosed with lung cancer between May 2013 and December 2015 in the Department of Thoracic Surgery, Tianjin 4th Centre Hospital, Tianjin, China were enrolled in this cross-sectional study. Patients were asked to complete the Symptom Checklist 90 (SCL-90) and Quality of Life Questionnaire (QLQ-C30) survey. From the responses, the correlation between the patient’s psychological status and QOL were analyzed with respect to several variables. Results: From the total of 258 patients subjected to the test, 168 belonged to the unhealthy psychology group and 90 to the healthy psychology group. Multiple regression analysis revealed that significant factors related to poor QOL among the 2 groups are gender (p=0.02), younger age (p=0.001), surgical history (p=0.04), employment status (p=0.03), and medical insurance (p=0.01) significantly predicted the severity of unhealthy psychology in lung cancer patients. A significantly negative correlation was noted between the points of SCL-90 and the general QOL in all included patients (p=0.03). Conclusion: Gender, younger age, surgical history, employment status, and medical insurance significantly predicted the severity of unhealthy psychology in lung cancer patients. PMID:28889154

Immunoglobulin-specific responses to Chlamydia elementary bodies in individuals with and at risk for genital chlamydial infection.

PubMed

Geisler, William M; Morrison, Sandra G; Doemland, Martha L; Iqbal, Shehzad M; Su, Jin; Mancevski, Ausra; Hook, Edward W; Morrison, Richard P

2012-12-15

Renewed interest in chlamydia vaccination has revealed the need for a greater understanding of the seroprevalence of chlamydial infection in US populations. We used a Chlamydia trachomatis elementary body (EB)-based enzyme-linked immunosorbent assay to define the characteristics of the humoral immune response and to determine seroprevalence. Two groups were analyzed: one consisting of patients with current, laboratory confirmed, genital chlamydial infection (n = 98) and one group of individuals whose chlamydia infection history was unknown (n = 367). C. trachomatis seropositivity was detected in 90% of the infected group and in 31% of the chlamydia-unknown group. IgG1 and IgG3 comprised the predominant anti-Chlamydia serum antibody responses. Serum IgA1 responses were variably positive, and individuals were rarely positive for anti-chlamydia IgG2, IgG4 or IgA2. The magnitude of the IgG1 and IgG3 responses was greatest in female and African American individuals and was sustained for at least 6 months. Antibody responses were not serovar restricted or confounded by Chlamydia pneumoniae cross-reactivity.

Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.

PubMed

Lampaki, Sofia; Lazaridis, George; Zarogoulidis, Konstantinos; Kioumis, Ioannis; Papaiwannou, Antonis; Tsirgogianni, Katerina; Karavergou, Anastasia; Tsiouda, Theodora; Karavasilis, Vasilis; Yarmus, Lonny; Darwiche, Kaid; Freitag, Lutz; Sakkas, Antonios; Kantzeli, Angeliki; Baka, Sofia; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul

2015-01-01

Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the

Imaging in lung transplants: Checklist for the radiologist.

PubMed

Madan, Rachna; Chansakul, Thanissara; Goldberg, Hilary J

2014-10-01

Post lung transplant complications can have overlapping clinical and imaging features, and hence, the time point at which they occur is a key distinguisher. Complications of lung transplantation may occur along a continuum in the immediate or longer postoperative period, including surgical and mechanical problems due to size mismatch and vascular as well as airway anastomotic complication, injuries from ischemia and reperfusion, acute and chronic rejection, pulmonary infections, and post-transplantation lymphoproliferative disorder. Life expectancy after lung transplantation has been limited primarily by chronic rejection and infection. Multiple detector computed tomography (MDCT) is critical for evaluation and early diagnosis of complications to enable selection of effective therapy and decrease morbidity and mortality among lung transplant recipients.

Chlamydia gallinacea, not C. psittaci, is the endemic chlamydial species in chicken (Gallus gallus).

PubMed

Guo, Weina; Li, Jing; Kaltenboeck, Bernhard; Gong, Jiansen; Fan, Weixing; Wang, Chengming

2016-01-18

To investigate the prevalence and diversity of Chlamydia spp. in domestic birds in China, oral and cloacal swabs of healthy chickens, ducks, geese and pigeons were collected nationwide from live-animal markets and examined by Chlamydia spp. 23 S rRNA gene FRET-PCR followed by high-resolution melting curve analysis and confirmatory sequencing. Overall, 26.2% of the birds (602/2,300) were positive for Chlamydia spp. and five Chlamydia spp. were identified. While occasional detection of C. suis and C. muridarum in poultry is reported here for the first time, the predominant chlamydial agent was C. gallinacea representing 63.8% of all positives (384/602) and 81.2% of positive chickens (359/442). Analysis of the C. gallinacea ompA phylogeny revealed at least 13 well segregated variants (serovars). Seven-month monitoring of C. gallinacea-infected chickens indicated that the infection was persistent. C. gallinacea-infected chickens remained without overt clinical disease, but showed body weight gains significantly reduced by 6.5-11.4% beginning in week 3 post-infection. This study indicates that C. gallinacea is the endemic chlamydial species in chickens, whereas C. psittaci dominates only in pigeons. Further studies are required to address the specific conditions under which C. gallinacea could act as an avian pathogen and possibly also a zoonotic agent.

Chlamydia gallinacea, not C. psittaci, is the endemic chlamydial species in chicken (Gallus gallus)

PubMed Central

Guo, Weina; Li, Jing; Kaltenboeck, Bernhard; Gong, Jiansen; Fan, Weixing; Wang, Chengming

2016-01-01

To investigate the prevalence and diversity of Chlamydia spp. in domestic birds in China, oral and cloacal swabs of healthy chickens, ducks, geese and pigeons were collected nationwide from live-animal markets and examined by Chlamydia spp. 23 S rRNA gene FRET-PCR followed by high-resolution melting curve analysis and confirmatory sequencing. Overall, 26.2% of the birds (602/2,300) were positive for Chlamydia spp. and five Chlamydia spp. were identified. While occasional detection of C. suis and C. muridarum in poultry is reported here for the first time, the predominant chlamydial agent was C. gallinacea representing 63.8% of all positives (384/602) and 81.2% of positive chickens (359/442). Analysis of the C. gallinacea ompA phylogeny revealed at least 13 well segregated variants (serovars). Seven-month monitoring of C. gallinacea-infected chickens indicated that the infection was persistent. C. gallinacea-infected chickens remained without overt clinical disease, but showed body weight gains significantly reduced by 6.5–11.4% beginning in week 3 post-infection. This study indicates that C. gallinacea is the endemic chlamydial species in chickens, whereas C. psittaci dominates only in pigeons. Further studies are required to address the specific conditions under which C. gallinacea could act as an avian pathogen and possibly also a zoonotic agent. PMID:26778053

Establishing homology between mitochondrial calcium uniporters, prokaryotic magnesium channels and chlamydial IncA proteins.

PubMed

Lee, Andre; Vastermark, Ake; Saier, Milton H

2014-08-01

Mitochondrial calcium uniporters (MCUs) (TC no. 1.A.77) are oligomeric channel proteins found in the mitochondrial inner membrane. MCUs have two well-conserved transmembrane segments (TMSs), connected by a linker, similar to bacterial MCU homologues. These proteins and chlamydial IncA proteins (of unknown function; TC no. 9.B.159) are homologous to prokaryotic Mg(2+) transporters, AtpI and AtpZ, based on comparison scores of up to 14.5 sds. A phylogenetic tree containing all of these proteins showed that the AtpZ proteins cluster coherently as a subset within the large and diverse AtpI cluster, which branches separately from the MCUs and IncAs, both of which cluster coherently. The MCUs and AtpZs share the same two TMS topology, but the AtpIs have four TMSs, and IncAs can have either two (most frequent) or four (less frequent) TMSs. Binary alignments, comparison scores and motif analyses showed that TMSs 1 and 2 align with TMSs 3 and 4 of the AtpIs, suggesting that the four TMS AtpI proteins arose via an intragenic duplication event. These findings establish an evolutionary link interconnecting eukaryotic and prokaryotic Ca(2+) and Mg(2+) transporters with chlamydial IncAs, and lead us to suggest that all members of the MCU superfamily, including IncAs, function as divalent cation channels. © 2014 The Authors.

Establishing homology between mitochondrial calcium uniporters, prokaryotic magnesium channels and chlamydial IncA proteins

PubMed Central

Lee, Andre; Vastermark, Ake

2014-01-01

Mitochondrial calcium uniporters (MCUs) (TC no. 1.A.77) are oligomeric channel proteins found in the mitochondrial inner membrane. MCUs have two well-conserved transmembrane segments (TMSs), connected by a linker, similar to bacterial MCU homologues. These proteins and chlamydial IncA proteins (of unknown function; TC no. 9.B.159) are homologous to prokaryotic Mg2+ transporters, AtpI and AtpZ, based on comparison scores of up to 14.5 sds. A phylogenetic tree containing all of these proteins showed that the AtpZ proteins cluster coherently as a subset within the large and diverse AtpI cluster, which branches separately from the MCUs and IncAs, both of which cluster coherently. The MCUs and AtpZs share the same two TMS topology, but the AtpIs have four TMSs, and IncAs can have either two (most frequent) or four (less frequent) TMSs. Binary alignments, comparison scores and motif analyses showed that TMSs 1 and 2 align with TMSs 3 and 4 of the AtpIs, suggesting that the four TMS AtpI proteins arose via an intragenic duplication event. These findings establish an evolutionary link interconnecting eukaryotic and prokaryotic Ca2+ and Mg2+ transporters with chlamydial IncAs, and lead us to suggest that all members of the MCU superfamily, including IncAs, function as divalent cation channels. PMID:24869855

Chemical defense of early life stages of benthic marine invertebrates.

PubMed

Lindquist, Niels

2002-10-01

Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

Effects of early life factors on the health and quality of life of older adults.

PubMed

Yilmaz, Fikriye; N Tekin, Rukiye

2018-01-01

Few studies on the effects of early life factors on the health and quality of life of adults have been conducted in Turkey. We aimed to investigate the effects of early life factors on the health and quality of life of older adults. We administered a questionnaire to 350 adults, aged 50-89 years, living in Cankaya, Ankara. The questionnaire covered sociodemographic characteristics, early life characteristics, health status, and the World Health Organization Quality of Life-Ageing scale. Data were analyzed using χ 2 tests, independent samples t-tests, one-way anova, and binary logistic regression analysis. The analyses showed that the most important risk factors for chronic disease were being ≥65 years (odds ratio (OR) = 2.34), having a chronic health problem before 18 years of age (OR = 2.48), experiencing prolonged hospitalization or bed rest before 18 years of age (OR = 2.65), and experiencing parental unconcern during early life (OR = 2.13) (P < 0.05). In addition, having a high school education or less includes people who have primary or secondary or high school diploma (OR = 1.65), having lived in a village (OR = 1.65), having a low family economic status (OR = 2.40), and having experienced one negative event (OR = 1.41) or two or more negative events (OR = 1.39) during their early lives were identified as important risk factors for low quality of life (P < 0.05). Early life factors are among the important determinants of the health and quality of life of older adults in Turkey. © 2017 Japanese Psychogeriatric Society.

Early-Life Origins of the Race Gap in Men's Mortality

ERIC Educational Resources Information Center

Warner, David F.; Hayward, Mark D.

2006-01-01

Using a life course framework, we examine the early life origins of the race gap in men's all-cause mortality. Using the National Longitudinal Survey of Older Men (1966-1990), we evaluate major social pathways by which early life conditions differentiate the mortality experiences of blacks and whites. Our findings indicate that early life…

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Early results in transplantation of initially rejected donor lungs after ex vivo lung perfusion: a case-control study.

PubMed

Wallinder, Andreas; Ricksten, Sven-Erik; Silverborn, Martin; Hansson, Christoffer; Riise, Gerdt C; Liden, Hans; Jeppsson, Anders; Dellgren, Göran

2014-01-01

An increasing number of studies have shown that ex vivo lung perfusion (EVLP) is safe and that rejected donor lungs can be resuscitated and used for lung transplantation (LTx). Early clinical outcomes in patients transplanted with reconditioned lungs at our centre were reviewed and compared with those of contemporary non-EVLP controls. During 18 months starting January 2011, 11 pairs of donor lungs initially deemed unsuitable for transplantation underwent EVLP. Haemodynamic (pulmonary flow, vascular resistance and artery pressure) and respiratory (peak airway pressure and compliance) parameters were analysed during evaluation. Lungs that improved (n = 11) to meet International Society of Heart and Lung Transplantation criteria were transplanted and compared with patients transplanted with non-EVLP lungs (n = 47) during the same time period. Donor lungs were initially rejected due to either inferior PaO2/FiO2 ratio (n = 9), bilateral infiltrate on chest X-ray (n = 1) or ongoing extra corporeal membrane oxygenation (n = 1). The donor lungs improved from a mean PaO2/FiO2 ratio of 27.9 kPa in the donor to a mean of 59.6 kPa at the end of the EVLP (median improvement 28.4 kPa, range 21.0-50.7 kPa). Two single lungs were deemed unsuitable and not used for LTx. Eleven recipients from the regular waiting list underwent either single (n = 3) LTx or double (n = 8) LTx with EVLP-treated lungs. The median time to extubation (12 (range, 3-912) vs 6 (range, 2-1296) h) and median intensive care unit (ICU) stay (152 (range, 40-625) vs 48 (range, 22-1632) h) were longer in the EVLP group (P = 0.05 and P = 0.01, respectively). There were no differences in length of hospital stay (median 28 (range 25-93) vs 28 (18-209), P = 0.21). Two patients in the EVLP group and 6 in the control group had primary graft dysfunction >Grade 1 at 72 h postoperatively. Three patients in the control group died before discharge. All recipients of EVLP lungs were discharged alive from hospital. The use of

Use of laboratory testing for genital chlamydial infection in Norway.

PubMed Central

Aavitsland, P

1993-01-01

OBJECTIVE--To assess the use of laboratory tests for genital chlamydial infection in Norway. DESIGN--Questionnaire survey of general practitioners' practice in chlamydial testing, retrospective survey of laboratory records, 1986-91, and prospective study of testing in one laboratory during four weeks. SETTING--All 18 microbiological laboratories in Norway (4.2 million population), including one serving all doctors in Vestfold county (0.2 million population). SUBJECTS--302 general practitioners. MAIN MEASURES--GPs' routine practice, methods used for testing, 1986-91, and sex specific and age group specific testing in 1991. RESULTS--201(69%) GPs replied to the questionnaire: 101(51%) would test all women younger than 25 years at routine pelvic examination, 107(54%) all girls at first pelvic examination, 131(66%) all pregnant women, and 106(54%) all men whose female partner had urogenital complaints. Nationwide in 1986, 122,000 tests were performed (2.9 per 100 population); 10% were positive and 51% were cell culture tests. In 1991, 341,000 tests were performed (8.0 per 100 population); 4.5% were positive and 15% were cell culture tests. 13,184 tests were performed in Vestfold in 1991 (6.6 per 100 population). The age group specific rates (per 100 population) among women were: age 15-19 years, 22.0(95% confidence interval 18.2 to 25.8); 20-24 years, 47.2(42.1 to 52.3); 25-29 years, 42.3(37.1 to 47.5); 30-34 years, 29.8(25.4 to 34.2); and 35-39 years, 12.5(9.5 to 15.5). CONCLUSIONS--GPs use liberal indications for testing. The dramatic increase in testing, especially by enzyme immunoassays, in populations with a low prevalence of infection results in low cost effectiveness and low predictive value of positive tests, which in women over 29 years is estimated as 17-36%. IMPLICATIONS--Doctors should be educated about the limitations of enzyme immunoassays in screening low prevalence populations, and laboratories should apply a confirmatory test to specimens testing

Timing of palliative care needs reporting and aggressiveness of care near the end of life in metastatic lung cancer: A national registry-based study.

PubMed

Goldwasser, François; Vinant, Pascale; Aubry, Régis; Rochigneux, Philippe; Beaussant, Yvan; Huillard, Olivier; Morin, Lucas

2018-05-09

Early integration of palliative care for patients with metastatic lung cancer improves their quality of life and survival and reduces the aggressiveness of care near the end of life. This study examined the association between the timing of palliative care needs reporting and the aggressiveness of end-of-life care. This retrospective cohort study used the French National Hospital Registry to identify all hospitalized adults (≥20 years old) who died of metastatic lung cancer in France between 2010 and 2013. It compared the use of care and treatments near the end of life as a function of the timing of the first reporting of palliative care needs. The use of chemotherapy and the use of invasive ventilation were defined as primary outcomes. Propensity score weighting was used to control for potential confounders. Among a total of 64,950 deceased patients with metastatic lung cancer, the reporting of palliative care needs was characterized as timely (from 91 to 31 days before death) for 26.3%, late (from 30 to 8 days before death) for 31.5%, and very late (from 7 to 0 days before death) for 12.8%. Palliative care needs were not reported for 19,106 patients (29.4%). Patients with timely reporting of palliative care needs had the earliest and most progressive decrease in the use of anticancer therapy. The use of invasive ventilation also increased with a delay in palliative care needs reporting. There is a clear association between the timing of palliative care needs reporting and the aggressiveness of care near the end of life. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK?

PubMed

O'Dowd, Emma L; McKeever, Tricia M; Baldwin, David R; Anwar, Sadia; Powell, Helen A; Gibson, Jack E; Iyen-Omofoman, Barbara; Hubbard, Richard B

2015-02-01

The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis. All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice. Of 20,142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65-69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths. Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of Mindfulness Training on Asthma Quality of Life and Lung Function: A Randomized Controlled Trial

PubMed Central

Pbert, Lori; Madison, J. Mark; Druker, Susan; Olendzki, Nicholas; Magner, Robert; Reed, George; Carmody, James

2014-01-01

Background Improving asthma patients’ quality of life is an important clinical outcome. This study evaluated the efficacy of mindfulness-based stress reduction (MBSR) in improving quality of life and lung function in patients with asthma. Methods A randomized controlled trial compared an 8 week MBSR group-based program (n = 42) to an educational control program (n = 41) in adults with mild, moderate or severe persistent asthma recruited at a university hospital outpatient primary care and pulmonary care clinic. Primary outcomes were quality of life assessed by the Asthma Quality of Life Questionnaire (AQOL), and lung function assessed by change from baseline in two-week average morning peak expiratory flow (PEF). Secondary outcomes were asthma control assessed by 2007 NIH/NHLBI guidelines, and stress assessed by Perceived Stress Scale. Follow-up assessments were conducted at 10 weeks, 6 and 12 months. Results At 12 months MBSR resulted in clinically significant improvements in quality of life (intervention effect 0.55 (95% CI 0.21, 0.89, p=0.001)) and perceived stress (intervention effect −4.5 (95% CI −7.1, −1.9; p= 0.001)). No significant effect was found on lung function (morning PEF, PEF variability, and FEV1). At 12 months the percentage of patients in MBSR with well-controlled asthma showed a non-statistically significant increase (7.3% at baseline to 19.4%) compared to the control condition (7.5% and 7.9%, respectively) (p=0.30). Conclusions MBSR produced lasting clinically significant improvements in asthma-related quality of life and stress in patients with persistent asthma, even in the absence of improvements in lung function. PMID:22544892

A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer.

PubMed

Halvorsen, Ann Rita; Bjaanæs, Maria; LeBlanc, Marissa; Holm, Are M; Bolstad, Nils; Rubio, Luis; Peñalver, Juan Carlos; Cervera, José; Mojarrieta, Julia Cruz; López-Guerrero, Jose Antonio; Brustugun, Odd Terje; Helland, Åslaug

2016-06-14

Circulating microRNAs are promising biomarkers for diagnosis, predication and prognostication of diseases. Lung cancer is the cancer disease accountable for most cancer deaths, largely due to being diagnosed at late stages. Therefore, diagnosing lung cancer patients at an early stage is crucial for improving the outcome. The purpose of this study was to identify circulating microRNAs for detection of early stage lung cancer, capable of discriminating lung cancer patients from those with chronic obstructive pulmonary disease (COPD) and healthy volunteers. We identified 7 microRNAs separating lung cancer patients from controls. By using RT-qPCR, we validated 6 microRNAs (miR-429, miR-205, miR-200b, miR-203, miR-125b and miR-34b) with a significantly higher abundance in serum from NSCLC patients. Furthermore, the 6 miRNAs were validated in a different dataset, revealing an area under the receiver operating characteristic curve of 0.89 for stage I-IV and 0.88 for stage I/II. We profiled the expression of 754 unique microRNAs by TaqMan Low Density Arrays, and analyzed serum from 38 patients with NSCLC, 16 patients suffering from COPD and 16 healthy volunteers from Norway, to explore their potential as diagnostic biomarkers. For validation, we analyzed serum collected from high-risk individuals enrolled in the Valencia branch of the International Early Lung Cancer Action Program screening trial (n=107) in addition to 51 lung cancer patients. Considering the accessibility and stability of circulating miRNAs, these 6 microRNAs are promising biomarkers as a supplement in future screening studies.

Chlamydia pneumoniae effector chlamydial outer protein N sequesters fructose bisphosphate aldolase A, providing a benefit to bacterial growth.

PubMed

Ishida, Kasumi; Matsuo, Junji; Yamamoto, Yoshimasa; Yamaguchi, Hiroyuki

2014-12-21

Pathogenic chlamydiae are obligate intracellular pathogens and have adapted successfully to human cells, causing sexually transmitted diseases or pneumonia. Chlamydial outer protein N (CopN) is likely a critical effector protein secreted by the type III secretion system in chlamydiae, which manipulates host cells. However, the mechanisms of its action remain to be clarified. In this work, we aimed to identify previously unidentified CopN effector target in host cells. We first performed a pull-down assay with recombinant glutathione S-transferase (GST) fusion CopN proteins (GST-CpCopN: Chlamydia pneumoniae TW183, GST-CtCopN: Chlamydia trachomatis D/UW-3/CX) as "bait" and soluble lysates obtained from human immortal epithelial HEp-2 cells as "prey", followed by SDS-PAGE with mass spectroscopy (MS). We found that a host cell protein specifically bound to GST-CpCopN, but not GST-CtCopN. MS revealed the host protein to be fructose bisphosphate aldolase A (aldolase A), which plays a key role in glycolytic metabolism. We also confirmed the role of aldolase A in chlamydia-infected HEp-2 cells by using two distinct experiments for gene knockdown with an siRNA specific to aldolase A transcripts, and for assessment of glycolytic enzyme gene expression levels. As a result, both the numbers of chlamydial inclusion-forming units and RpoD transcripts were increased in the chlamydia-infected aldolase A knockdown cells, as compared with the wild-type HEp-2 cells. Meanwhile, chlamydial infection tended to enhance expression of aldolase A. We discovered that one of the C. pneumoniae CopN targets is the glycolytic enzyme aldolase A. Sequestering aldolase A may be beneficial to bacterial growth in infected host cells.

Before the first breath: prenatal exposures to air pollution and lung development.

PubMed

Veras, Mariana Matera; de Oliveira Alves, Nilmara; Fajersztajn, Lais; Saldiva, Paulo

2017-03-01

Various environmental contaminants are known to impair the growth trajectories of major organs, indirectly (gestational exposure) or directly (postnatal exposure). Evidence associates pre-gestational and gestational exposure to air pollutants with adverse birth outcomes (e.g., low birth weight, prematurity) and with a wide range of diseases in childhood and later in life. In this review, we explore the way that pre-gestational and gestational exposure to air pollution affects lung development. We present results in topics underlining epidemiological and toxicological evidence. We also provide a summary of the biological mechanisms by which air pollution exposure possibly leads to adverse respiratory outcomes. We conclude that gestational and early life exposure to air pollutants are linked to alterations in lung development and function and to other negative respiratory conditions in childhood (wheezing, asthma) that may last into adulthood. Plausible mechanisms encompass changes in maternal physiology (e.g., hypoxia, oxidative stress and inflammation) and DNA alterations in the fetus. Evidence for pre-gestational and gestational effects on the lung is scarce compared with that on early life exposure and further studies are needed. However, the suggested mechanisms are credible and the evidence of pre-gestational and gestational air pollution exposure is robust for adverse birth outcomes. Air pollutants might change lung developmental trajectories of the unborn child predisposing it to diseases later in life highlighting the urgent need for controls on urban air pollution levels worldwide.

Stereotactic radiotherapy for early lung cancer: Evidence-based approach and future directions

PubMed Central

Chehade, Samer; Palma, David A.

2015-01-01

Aim To review key studies evaluating stereotactic radiotherapy in the setting of early-stage non-small cell lung cancer (NSCLC) for inoperable or high-risk patients, and discuss areas of ongoing research and clinical trials. Background The use of stereotactic radiotherapy for the treatment of early stage non-small cell lung cancer (NSCLC) has increased rapidly over the past decade. Numerous studies have reported outcomes for patients treated with SBRT who are unfit for surgical resection, or at high risk of surgical complications. Materials and methods A narrative review. Results The preponderance of evidence suggests that SBRT is associated with excellent local control (∼90% at 3 years) and a favorable toxicity profile. In patients with higher operative risks, such as the elderly and patients with severe COPD, SBRT may provide a less-toxic treatment than surgery with similar oncologic outcomes. Ongoing studies are evaluating the use of SBRT for locally advanced or oligometastatic NSCLC. Conclusions A large body of evidence now exists to support the use of SBRT for early-stage NSCLC. Decisions regarding the optimal choice of treatment should be individualized, and made in the context of a multidisciplinary team. PMID:26696779

Following the Footsteps of Chlamydial Gene Regulation

PubMed Central

Domman, D.; Horn, M.

2015-01-01

Regulation of gene expression ensures an organism responds to stimuli and undergoes proper development. Although the regulatory networks in bacteria have been investigated in model microorganisms, nearly nothing is known about the evolution and plasticity of these networks in obligate, intracellular bacteria. The phylum Chlamydiae contains a vast array of host-associated microbes, including several human pathogens. The Chlamydiae are unique among obligate, intracellular bacteria as they undergo a complex biphasic developmental cycle in which large swaths of genes are temporally regulated. Coupled with the low number of transcription factors, these organisms offer a model to study the evolution of regulatory networks in intracellular organisms. We provide the first comprehensive analysis exploring the diversity and evolution of regulatory networks across the phylum. We utilized a comparative genomics approach to construct predicted coregulatory networks, which unveiled genus- and family-specific regulatory motifs and architectures, most notably those of virulence-associated genes. Surprisingly, our analysis suggests that few regulatory components are conserved across the phylum, and those that are conserved are involved in the exploitation of the intracellular niche. Our study thus lends insight into a component of chlamydial evolution that has otherwise remained largely unexplored. PMID:26424812

Early detection of lung cancer from CT images: nodule segmentation and classification using deep learning

NASA Astrophysics Data System (ADS)

Sharma, Manu; Bhatt, Jignesh S.; Joshi, Manjunath V.

2018-04-01

Lung cancer is one of the most abundant causes of the cancerous deaths worldwide. It has low survival rate mainly due to the late diagnosis. With the hardware advancements in computed tomography (CT) technology, it is now possible to capture the high resolution images of lung region. However, it needs to be augmented by efficient algorithms to detect the lung cancer in the earlier stages using the acquired CT images. To this end, we propose a two-step algorithm for early detection of lung cancer. Given the CT image, we first extract the patch from the center location of the nodule and segment the lung nodule region. We propose to use Otsu method followed by morphological operations for the segmentation. This step enables accurate segmentation due to the use of data-driven threshold. Unlike other methods, we perform the segmentation without using the complete contour information of the nodule. In the second step, a deep convolutional neural network (CNN) is used for the better classification (malignant or benign) of the nodule present in the segmented patch. Accurate segmentation of even a tiny nodule followed by better classification using deep CNN enables the early detection of lung cancer. Experiments have been conducted using 6306 CT images of LIDC-IDRI database. We achieved the test accuracy of 84.13%, with the sensitivity and specificity of 91.69% and 73.16%, respectively, clearly outperforming the state-of-the-art algorithms.

SU-F-R-24: Identifying Prognostic Imaging Biomarkers in Early Stage Lung Cancer Using Radiomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, X; Wu, J; Cui, Y

2016-06-15

Purpose: Patients diagnosed with early stage lung cancer have favorable outcomes when treated with surgery or stereotactic radiotherapy. However, a significant proportion (∼20%) of patients will develop metastatic disease and eventually die of the disease. The purpose of this work is to identify quantitative imaging biomarkers from CT for predicting overall survival in early stage lung cancer. Methods: In this institutional review board-approved HIPPA-compliant retrospective study, we retrospectively analyzed the diagnostic CT scans of 110 patients with early stage lung cancer. Data from 70 patients were used for training/discovery purposes, while those of remaining 40 patients were used for independentmore » validation. We extracted 191 radiomic features, including statistical, histogram, morphological, and texture features. Cox proportional hazard regression model, coupled with the least absolute shrinkage and selection operator (LASSO), was used to predict overall survival based on the radiomic features. Results: The optimal prognostic model included three image features from the Law’s feature and wavelet texture. In the discovery cohort, this model achieved a concordance index or CI=0.67, and it separated the low-risk from high-risk groups in predicting overall survival (hazard ratio=2.72, log-rank p=0.007). In the independent validation cohort, this radiomic signature achieved a CI=0.62, and significantly stratified the low-risk and high-risk groups in terms of overall survival (hazard ratio=2.20, log-rank p=0.042). Conclusion: We identified CT imaging characteristics associated with overall survival in early stage lung cancer. If prospectively validated, this could potentially help identify high-risk patients who might benefit from adjuvant systemic therapy.« less

Socioeconomic Factors Are Associated With Readmission After Lobectomy for Early Stage Lung Cancer.

PubMed

Medbery, Rachel L; Gillespie, Theresa W; Liu, Yuan; Nickleach, Dana C; Lipscomb, Joseph; Sancheti, Manu S; Pickens, Allan; Force, Seth D; Fernandez, Felix G

2016-11-01

Data regarding risk factors for readmissions after surgical resection for lung cancer are limited and largely focus on postoperative outcomes, including complications and hospital length of stay. The current study aims to identify preoperative risk factors for postoperative readmission in early stage lung cancer patients. The National Cancer Data Base was queried for all early stage lung cancer patients with clinical stage T2N0M0 or less who underwent lobectomy in 2010 and 2011. Patients with unplanned readmission within 30 days of hospital discharge were identified. Univariate analysis was utilized to identify preoperative differences between readmitted and not readmitted cohorts; multivariable logistic regression was used to identify risk factors resulting in readmission. In all, 840 of 19,711 patients (4.3%) were readmitted postoperatively. Male patients were more likely to be readmitted than female patients (4.9% versus 3.8%, p < 0.001), as were patients who received surgery at a nonacademic rather than an academic facility (4.6% versus 3.6%; p = 0.001) and had underlying medical comorbidities (Charlson/Deyo score 1+ versus 0; 4.8% versus 3.7%; p < 0.001). Readmitted patients had a longer median hospital length of stay (6 days versus 5; p < 0.001) and were more likely to have undergone a minimally invasive approach (5.1% video-assisted thoracic surgery versus 3.9% open; p < 0.001). In addition to those variables, multivariable logistic regression analysis identified that median household income level, insurance status (government versus private), and geographic residence (metropolitan versus urban versus rural) had significant influence on readmission. The socioeconomic factors identified significantly influence hospital readmission and should be considered during preoperative and postoperative discharge planning for patients with early stage lung cancer. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Role and Importance of Chlamydia Trachomatis in Pregnant Patients

PubMed Central

Angelova, Mariya; Kovachev, Emil; Tsankova, Veselina; Koleva, Iliana; Mangarova, Silvia

2016-01-01

AIM: The aim of this study was to assess the prevalence of chlamydial infection among pregnant women and to determine the role of this infection in the fetus. MATERIAL AND METHODS: In the first phase of this study were reported 58 pregnant women with a positive test for active chlamydial infection by applying immunofluorescence. In the second phase of the study were reported pregnant with premature burst membranes (PBM), postnatal complications associated with chlamydial infection as puerperal endometritis, and newborns are monitored for low birth weight and growth retardation at birth. RESULTS: With a positive test are 58 patients in the first trimester or pregnancy registration in our consultation. After regimen with Sumamed (2 x 500 mg for three days and after 10 days again same scheme for them and their partner) at the beginning of the third trimester, the PCR test was made again. Of these, 5 were positive again, participants are between 20 and 30 years old. With premature rupture of OM are 20 patients. There was no increased incidence of premature births. Infants born to infected mothers have a higher risk of developing respiratory symptoms in the first 60 days of life. 3 of them have low for his age bodyweight. CONCLUSIONS: The scarcity of data on manifestations of chlamydial infection during pregnancy and neonatal outcomes justifies this study. Early diagnosis for registration of pregnancy and timely treatment of chlamydial infection as well as scrutinising the infection during the third trimester of pregnancy can prevent infection of the newborn. Therefore, preventive examinations should be considered as a priority for early detection of asymptomatic chlamydial infection in the conduct of antenatal care. PMID:27703564

The Intestinal Microbiome in Early Life: Health and Disease

PubMed Central

Arrieta, Marie-Claire; Stiemsma, Leah T.; Amenyogbe, Nelly; Brown, Eric M.; Finlay, Brett

2014-01-01

Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about 3 years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their health status as well as their immune system. An ever-expanding number of articles associate several diseases with early-life imbalances of the gut microbiota, also referred to as gut microbial dysbiosis. Whether early-life dysbiosis precedes and plays a role in disease pathogenesis, or simply originates from the disease process itself is a question that is beginning to be answered in a few diseases, including IBD, obesity, and asthma. This review describes the gut microbiome structure and function during the formative first years of life, as well as the environmental factors that determine its composition. It also aims to discuss the recent advances in understanding the role of the early-life gut microbiota in the development of immune-mediated, metabolic, and neurological diseases. A greater understanding of how the early-life gut microbiota impacts our immune development could potentially lead to novel microbial-derived therapies that target disease prevention at an early age. PMID:25250028

Comment from the Editor to the Special Issue: “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis”

PubMed Central

Spaggiari, Lorenzo

2018-01-01

With this Editorial we want to present the Special Issue “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis” to the scientific community, which aims to gather experts on the early detection of lung cancer in order to implement common efforts in the fight against cancer. PMID:29425180

Trans-Agency Early-Life Exposures and Cancer Working Group

Cancer.gov

The Trans-Agency Early-Life Exposures and Cancer Working Group promotes integration of early-life events and exposures into public health cancer research, control, prevention, and policy strategies to reduce the cancer burden in the United States and globally.

Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease.

PubMed

Rehkopf, David H; Eisen, Ellen A; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F; Slade, Martin D; Cullen, Mark R

2015-08-01

We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

PubMed Central

Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

2015-01-01

Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

PubMed Central

2013-01-01

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response

Development of Life on Early Mars

NASA Technical Reports Server (NTRS)

Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

2009-01-01

Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

Sex differences in the consequences of early-life exposure to epidemiological stress--a life-history approach.

PubMed

Störmer, Charlotte

2011-01-01

Exposure to infectious disease in early life has been suggested to have a negative effect on later-life survival,possibly through the induction of inflammatory responses. Although a life-course perspective emphasizes the importance of both survival and reproduction for individual fitness, to date, no studies have investigated whether early-life exposure to infectious disease has an impact on reproduction as it has been suggested for later survival. To address this question, I have used family reconstitution data from a historical (18th and 19th century) human population in the Krummhörn (Germany) comparing survival and reproduction between an exposed and a non-exposed group. The exposed group comprised those exposed to a high-infectious disease load during prenatal and early postnatal development. The results show a marked sex difference in the impact of early-life exposure to infectious disease. Exposed females show no effect on their life expectancy but significantly reduced fertility (number of children). For exposed males, however, the effect on survival is opponent over time: mortality is increased during childhood but decreased in late adulthood. Above that, exposed males reproduce earlier and have a smaller proportion of surviving children. This study does not support former studies indicating a negative association between early-life disease load and later survival. I argue that due to differences in male and female life strategies, males in general are more vulnerable especially early in life. Hence, adverse environmental conditions may have a stronger effect on male survivability and reproductive performance.

Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

PubMed

Ramsey, Kathryn A; Ranganathan, Sarath; Park, Judy; Skoric, Billy; Adams, Anne-Marie; Simpson, Shannon J; Robins-Browne, Roy M; Franklin, Peter J; de Klerk, Nick H; Sly, Peter D; Stick, Steve M; Hall, Graham L

2014-11-15

Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

PubMed

Dich, Nadya; Hansen, Åse Marie; Avlund, Kirsten; Lund, Rikke; Mortensen, Erik Lykke; Bruunsgaard, Helle; Rod, Naja Hulvej

2015-01-01

Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.

Early organ-specific mitochondrial dysfunction of jejunum and lung found in rats with experimental acute pancreatitis

PubMed Central

Mittal, Anubhav; Hickey, Anthony JR; Chai, Chau C; Loveday, Benjamin PT; Thompson, Nichola; Dare, Anna; Delahunt, Brett; Cooper, Garth JS; Windsor, John A; Phillips, Anthony RJ

2011-01-01

Introduction Multiple organ dysfunction is the main cause of death in severe acute pancreatitis. Primary mitochondrial dysfunction plays a central role in the development and progression of organ failure in critical illness. The present study investigated mitochondrial function in seven tissues during early experimental acute pancreatitis. Methods Twenty-eight male Wistar rats (463 ± 2 g; mean ± SEM) were studied. Group 1 (n = 8), saline control; Group 2 (n = 6), caerulein-induced mild acute pancreatitis; Group 3 (n = 7) sham surgical controls; and Group 4 (n = 7), taurocholate-induced severe acute pancreatitis. Animals were euthanased at 6 h from the induction of acute pancreatitis and mitochondrial function was assessed in the heart, lung, liver, kidney, pancreas, duodenum and jejunum by mitochondrial respirometry. Results Significant early mitochondrial dysfunction was present in the pancreas, lung and jejunum in both models of acute pancreatitis, however, the Heart, liver, kidney and duodenal mitochondria were unaffected. Conclusions The present study provides the first description of early organ-selective mitochondrial dysfunction in the lung and jejunum during acute pancreatitis. Research is now needed to identify the underlying pathophysiology behind the organ selective mitochondrial dysfunction, and the potential benefits of early mitochondrial-specific therapies in acute pancreatitis. PMID:21492333

Experimental Lung Cancer Drug Shows Early Promise | Frederick National Laboratory for Cancer Research

Cancer.gov

A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and

Commentary: On the Importance of Early Life Cognitive Abilities in Shaping Later Life Outcomes.

PubMed

Hofer, Scott M; Clouston, Sean

2014-01-01

Early life cognitive ability is likely to be dynamically related to life course factors including educational attainment, occupational outcomes, health behaviors, activities, health, and subsequent cognitive health. Disentangling the selective and causal processes contributing to cognitive functioning across the lifespan is challenging and requires long-term investments in longitudinal data. We discuss results from several analyses using data from the Individual Development and Adaptation longitudinal research program (Bergman, 2000; Magnusson, 1988) that provide fresh insights into the relation of early life cognition, particularly high levels of cognitive capabilities, to educational achievement, emotional adjustment, and career success. These papers and the longitudinal data provide a remarkable window into the development and impacts of cognition, and high cognitive functioning, on a variety of important life outcomes that we hope will continue to inform us about additional outcomes in middle life, transition to retirement, and cognition and health in later years and to robustly examine how the early years matter across the whole lifespan.

Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life

NASA Technical Reports Server (NTRS)

Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

2007-01-01

The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.3.9 Gy., (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

Palliative and end-of-life care in lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

PubMed

Ford, Dee Walker; Koch, Kathryn A; Ray, Daniel E; Selecky, Paul A

2013-05-01

In the United States, lung cancer is a major health problem that is associated with significant patient distress and often limited survival, with some exceptions. The purpose of this article is to address the role of palliative and end-of-life care in the management of patients with lung cancer and to address the need for good communication skills to provide support to patients and families. This article is based on an extensive review of the medical literature up to April 2012, with some articles as recent as August 2012. The authors used the PubMed and Cochrane databases, as well as EBESCO Host search, for articles addressing palliative care, supportive care, lung neoplasm, and quality of life in cancer or neoplasm, with no limitation on dates. The research was limited to human studies and the English language. There was no "definitive" work in this area, most of it being concurrence based rather than evidence based. Several randomized controlled trials were identified, which are reviewed in the text. The article focuses on the assessment and treatment of suffering in patients with lung cancer, as well as the importance of communication in the care of these patients over the course of the disease. The aim of medical care for patients with terminal lung cancer is to decrease symptom burden, enhance the quality of remaining life, and increase survival benefit. A second objective is to emphasize the importance of good communication skills when addressing the needs of the patient and his or her family, starting at the time of diagnosis, which in itself is a life-changing event. Too often we do it poorly, but by using patient-centered communication skills, the outcome can be more satisfactory. Finally, the article addresses the importance of advance care planning for patients with lung cancer, from the time of diagnosis until the last phase of the illness, and it is designed to enhance the physician's role in facilitating this planning process. This article provides

Life Detection on the Early Earth

NASA Technical Reports Server (NTRS)

Runnegar, B.

2004-01-01

Finding evidence for first the existence, and then the nature of life on the early Earth or early Mars requires both the recognition of subtle biosignatures and the elimination of false positives. The history of the search for fossils in increasingly older Precambrian strata illustrates these difficulties very clearly, and new observational and theoretical approaches are both needed and being developed. At the microscopic level of investigation, three-dimensional morphological characterization coupled with in situ chemical (isotopic, elemental, structural) analysis is the desirable first step. Geological context is paramount, as has been demonstrated by the controversies over AH84001, the Greenland graphites, and the Apex chert microfossils . At larger scales, the nature of sedimentary bedforms and the structures they display becomes crucial, and here the methods of condensed matter physics prove most useful in discriminating between biological and non-biological constructions. Ultimately, a combination of geochemical, morphological, and contextural evidence may be required for certain life detection on the early Earth or elsewhere.

Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

PubMed Central

Watt, Richard G.; Tsakos, Georgios

2014-01-01

Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2015-09-01

SABR ) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W. Loo, Jr., M.D., Ph.D CONTRACTING ORGANIZATION: Stanford University Stanford, CA...CONTRACT NUMBER W81XWH-12-1-0236 Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer 5b. GRANT NUMBER 5c. PROGRAM...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Purpose and scope: Stereotactic ablative radiotherapy ( SABR ) has become a new standard of care for early

Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings.

PubMed

Dauphiné, David C; Ferreccio, Catterina; Guntur, Sandeep; Yuan, Yan; Hammond, S Katharine; Balmes, John; Smith, Allan H; Steinmaus, Craig

2011-08-01

Evidence suggests that arsenic in drinking water causes non-malignant lung disease, but nearly all data concern exposed adults. The desert city of Antofagasta (population 257,976) in northern Chile had high concentrations of arsenic in drinking water (>800 μg/l) from 1958 until 1970, when a new treatment plant was installed. This scenario, with its large population, distinct period of high exposure, and accurate data on past exposure, is virtually unprecedented in environmental epidemiology. We conducted a pilot study on early-life arsenic exposure and long-term lung function. We present these preliminary findings because of the magnitude of the effects observed. We recruited a convenience sample consisting primarily of nursing school employees in Antofagasta and Arica, a city with low drinking water arsenic. Lung function and respiratory symptoms in 32 adults exposed to >800 μg/l arsenic before age 10 were compared to 65 adults without high early-life exposure. Early-life arsenic exposure was associated with 11.5% lower forced expiratory volume in 1 s (FEV(1)) (P = 0.04), 12.2% lower forced vital capacity (FVC) (P = 0.04), and increased breathlessness (prevalence odds ratio = 5.94, 95% confidence interval 1.36-26.0). Exposure-response relationships between early-life arsenic concentration and adult FEV(1) and FVC were also identified (P trend = 0.03). Early-life exposure to arsenic in drinking water may have irreversible respiratory effects of a magnitude similar to smoking throughout adulthood. Given the small study size and non-random recruitment methods, further research is needed to confirm these findings.

Integrating Social Work into Palliative Care for Lung Cancer Patients and Families: A Multi-Dimensional Approach

PubMed Central

Otis-Green, Shirley; Sidhu, Rupinder K.; Ferraro, Catherine Del; Ferrell, Betty

2014-01-01

Lung cancer patients and their family caregivers face a wide range of potentially distressing symptoms across the four domains of quality of life. A multi-dimensional approach to addressing these complex concerns with early integration of palliative care has proven beneficial. This article highlights opportunities to integrate social work using a comprehensive quality of life model and a composite patient scenario from a large lung cancer educational intervention National Cancer Institute-funded program project grant. PMID:24797998

Prevention and management of lung cancer in China.

PubMed

Hong, Qun-Ying; Wu, Guo-Ming; Qian, Gui-Sheng; Hu, Cheng-Ping; Zhou, Jian-Ying; Chen, Liang-An; Li, Wei-Min; Li, Shi-Yue; Wang, Kai; Wang, Qi; Zhang, Xiao-Ju; Li, Jing; Gong, Xin; Bai, Chun-Xue

2015-09-01

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. © 2015 American Cancer Society.

Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation.

PubMed

Hofhuis, Ward; Hanekamp, Manon N; Ijsselstijn, Hanneke; Nieuwhof, Eveline M; Hop, Wim C J; Tibboel, Dick; de Jongste, Johan C; Merkus, Peter J F M

2011-03-01

To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation are lacking. Prospective longitudinal cohort study. Outpatient clinic of a tertiary level pediatric hospital. The cohort consisted of 64 infants; 33 received extracorporeal membrane oxygenation for meconium aspiration syndrome, 14 for congenital diaphragmatic hernia, four for sepsis, six for persistent pulmonary hypertension of the neonate, and seven for respiratory distress syndrome of infancy. Evaluation was at 6 mos and 12 mos; 39 infants were evaluated at both time points . None. Functional residual capacity and forced expiratory flow at functional residual capacity were measured and expressed as z score. Mean (sem) functional residual capacities in z score were 0.0 (0.2) and 0.2 (0.2) at 6 mos and 12 mos, respectively. Mean (sem) forced expiratory flow was significantly below average (z score = 0) (p < .001) at 6 mos and 12 mos: -1.1 (0.1) and -1.2 (0.1), respectively. At 12 mos, infants with diaphragmatic hernia had a functional residual capacity significantly above normal: mean (sem) z score = 1.2 (0.5). Infants treated with extracorporeal membrane oxygenation have normal lung volumes and stable forced expiratory flows within normal range, although below average, within the first year of life. There is reason to believe, therefore, that extracorporeal membrane oxygenation either ameliorates the harmful effects of mechanical ventilation or somehow preserves lung function in the very ill neonate.

Robotic-Assisted Thoracic Surgery for Early-Stage Lung Cancer: A Review.

PubMed

Brooks, Paula

2015-07-01

This review evaluates the benefits and disadvantages associated with the use of robotic-assisted technology in performing lobectomies in patients with early-stage lung cancer. The author conducted a literature search of Ovid®, MEDLINE®, PubMed®, and CINAHL® for articles published from 2005 to 2013. Search criteria included key terms such as robot, robotic, robotic-assisted lobectomy, and lung cancer. Of 922 articles, the author included a total of 12 research-based published studies in the analysis and incorporated the findings into an evidence table. Results showed that robotic-assisted lobectomies are feasible safe procedures for patients with stage 1A or 1B lung cancer; however, there is a steep learning curve and long-term randomized studies evaluating robotic-assisted lobectomy and conventional posterolateral thoracotomy or video-assisted thoracic lobectomy are needed. For patient safety, perioperative nurses should be aware of the length of time and experience required to perform these procedures, the costs, techniques, benefits, and disadvantages. Copyright © 2015 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury.

PubMed

Yasui, Hideki; Donahue, Deborah L; Walsh, Mark; Castellino, Francis J; Ploplis, Victoria A

2016-07-01

Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as early as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as early as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI. Copyright © 2016 the American Physiological Society.

Lung Metabolic Activation as an Early Biomarker of the Acute Respiratory Distress Syndrome and Local Gene Expression Heterogeneity

PubMed Central

Wellman, Tyler J.; de Prost, Nicolas; Tucci, Mauro; Winkler, Tilo; Baron, Rebecca M.; Filipczak, Piotr; Raby, Benjamin; Chu, Jen-hwa; Harris, R. Scott; Musch, Guido; dos Reis Falcao, Luiz F.; Capelozzi, Vera; Venegas, Jose; Melo, Marcos F. Vidal

2016-01-01

Background The acute respiratory distress syndrome (ARDS) is an inflammatory condition comprising diffuse lung edema and alveolar damage. ARDS frequently results from regional injury mechanisms. However, it is unknown whether detectable inflammation precedes lung edema and opacification, and whether topographically differential gene expression consistent with heterogeneous injury occurs in early ARDS. We aimed to determine the temporal relationship between pulmonary metabolic activation and density in a large animal model of early ARDS, and to assess gene expression in differentially activated regions. Methods We produced ARDS in sheep with intravenous LPS (10ng/kg/h) and mechanical ventilation for 20h. Using positron emission tomography, we assessed regional cellular metabolic activation with 2-deoxy-2-[(18)F]fluoro-D-glucose, perfusion and ventilation with 13NN-saline, and aeration using transmission scans. Species-specific micro-array technology was used to assess regional gene expression. Results Metabolic activation preceded detectable increases in lung density (as required for clinical diagnosis) and correlated with subsequent histological injury, suggesting its predictive value for severity of disease progression. Local time-courses of metabolic activation varied, with highly perfused and less aerated dependent lung regions activated earlier than non-dependent regions. These regions of distinct metabolic trajectories demonstrated differential gene expression for known and potential novel candidates for ARDS pathogenesis. Conclusions Heterogeneous lung metabolic activation precedes increases in lung density in the development of ARDS due to endotoxemia and mechanical ventilation. Local differential gene expression occurs in these early stages and reveals molecular pathways relevant to ARDS biology and of potential use as treatment targets. PMID:27611185

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

PubMed Central

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

Connective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection.

PubMed

Yee, John; Sadar, Marianne D; Sin, Don D; Kuzyk, Michael; Xing, Li; Kondra, Jennifer; McWilliams, Annette; Man, S F Paul; Lam, Stephen

2009-06-10

There are no reliable blood biomarkers to detect early lung cancer. We used a novel strategy that allows discovery of differentially present proteins against a complex and variable background. Mass spectrometry analyses of paired pulmonary venous-radial arterial blood from 16 lung cancer patients were applied to identify plasma proteins potentially derived from the tumor microenvironment. Two differentially expressed proteins were confirmed in 64 paired venous-arterial blood samples using an immunoassay. Twenty-eight pre- and postsurgical resection peripheral blood samples and two independent, blinded sets of plasma from 149 participants in a lung cancer screening study (49 lung cancers and 100 controls) and 266 participants from the National Heart Lung and Blood Institute Lung Health Study (45 lung cancer and 221 matched controls) determined the accuracy of the two protein markers to detect subclinical lung cancer. Connective tissue-activating peptide III (CTAP III)/ neutrophil activating protein-2 (NAP-2) and haptoglobin were identified to be significantly higher in venous than in arterial blood. CTAP III/NAP-2 levels decreased after tumor resection (P = .01). In two independent population cohorts, CTAP III/NAP-2 was significantly associated with lung cancer and improved the accuracy of a lung cancer risk prediction model that included age, smoking, lung function (FEV(1)), and an interaction term between FEV(1) and CTAP III/NAP-2 (area under the curve, 0.84; 95% CI, 0.77 to 0.91) compared to CAPIII/NAP-2 alone. We identified CTAP III/NAP-2 as a novel biomarker to detect preclinical lung cancer. The study underscores the importance of applying blood biomarkers as part of a multimodal lung cancer risk prediction model instead of as stand-alone tests.

Accounting Early for Life Long Learning: The AcE Project.

ERIC Educational Resources Information Center

University Coll. Worcester (England). Centre for Research in Early Childhood Education.

Building upon the work of the Effective Early Learning (EEL) Project in raising the quality of early learning for young children in the United Kingdom, the 3-year Accounting Early for Life Long Learning Project (AcE Project) focuses on enhancing in 3- to 6-year-olds those attitudes and dispositions that are important to life-long learning. This…

Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders

PubMed Central

Baram, Tallie Z.; Solodkin, Ana; Davis, Elysia P.; Stern, Hal; Obenaus, Andre; Sandman, Curt A.; Small, Steven L.

2012-01-01

Maternal sensory signals in early life play a crucial role in programming the structure and function of the developing brain, promoting vulnerability or resilience to emotional and cognitive disorders. In rodent models of early-life stress, fragmentation and unpredictability of maternally derived sensory signals provoke persistent cognitive and emotional dysfunction in offspring. Similar variability and inconsistency of maternal signals during both gestation and early postnatal human life may influence development of emotional and cognitive functions, including those that underlie later depression and anxiety. PMID:22885631

Early and late effects of aspirin and naproxen on microRNAs in the lung and blood of mice, either unexposed or exposed to cigarette smoke

PubMed Central

Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Camoirano, Anna; D'Agostini, Francesco; Geretto, Marta; Micale, Rosanna T.; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E.; De Flora, Silvio

2017-01-01

We recently showed that nonsteroidal anti-inflammatory drugs (NSAIDs) are able to inhibit the lung tumors induced by cigarette smoke, either mainstream (MCS) or environmental (ECS), in female mice. We used subsets of mice to analyze the expression of 1135 microRNAs in both lung and blood serum, as related to the whole-body exposure to smoke and/or oral administration of either aspirin or naproxen. In a first study, we evaluated early microRNA alterations in A/J mice exposed to ECS for 10 weeks, starting at birth, and/or treated with NSAIDs for 6 weeks, starting after weaning. At that time, when no histopathological change were apparent, ECS caused a considerable downregulation of pulmonary microRNAs affecting both adaptive mechanisms and disease-related pathways. Aspirin and naproxen modulated, with intergender differences, the expression of microRNAs having a variety of functions, also including regulation of cyclooxygenases and inflammation. In a second study, we evaluated late microRNA alterations in Swiss H mice exposed to MCS during the first 4 months of life and treated with NSAIDs after weaning until 7.5 months of life, when tumors were detected in mouse lung. Modulation of pulmonary microRNAs by the two NSAIDs was correlated with their ability to prevent preneoplastic lesions (microadenomas) and adenomas in the lung. In both studies, exposure to smoke and/or treatment with NSAIDs also modulated microRNA profiles in the blood serum. However, their levels were poorly correlated with those of pulmonary microRNAs, presumably because circulating microRNAs reflect the contributions from multiple organs and not only from lung. PMID:29156752

Effect of Early- and Adult-Life Socioeconomic Circumstances on Physical Inactivity.

PubMed

Cheval, Boris; Sieber, Stefan; Guessous, Idris; Orsholits, Dan; Courvoisier, Delphine S; Kliegel, Matthias; Stringhini, Silvia; Swinnen, Stephan P; Burton-Jeangros, Claudine; Cullati, Stéphane; Boisgontier, Matthieu P

2018-03-01

This study aimed to investigate the associations between early- and adult-life socioeconomic circumstances and physical inactivity (level and evolution) in aging using large-scale longitudinal data. This study used the Survey of Health Ageing and Retirement in Europe, a 10-yr population-based cohort study with repeated measurements in five waves, every 2 yr between 2004 and 2013. Self-reported physical inactivity (waves 1, 2, 4, and 5), household income (waves 1, 2, 4, and 5), educational attainment (wave of the first measurement occasion), and early-life socioeconomic circumstance (wave 3) were collected in 22,846 individuals 50 to 95 yr of age. Risk of physical inactivity was increased for women with the most disadvantaged early-life socioeconomic circumstances (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.20-1.86). With aging, the risk of physical inactivity increased for both sexes and was strongest for those with the most disadvantaged early-life socioeconomic circumstances (OR, 1.04 (95% CI, 1.02-1.06) for women; OR, 1.02 (95% CI, 1.00-1.05) for men), with the former effect being more robust than the latter one. The association between early-life socioeconomic circumstances and physical inactivity was mediated by adult-life socioeconomic circumstances, with education being the strongest mediator. Early-life socioeconomic circumstances predicted high levels of physical inactivity at older ages, but this effect was mediated by socioeconomic indicators in adult life. This finding has implications for public health policies, which should continue to promote education to reduce physical inactivity in people at older ages and to ensure optimal healthy aging trajectories, especially among women with disadvantaged early-life socioeconomic circumstances.

Endoscopic fluorescent diagnostics and PDT of early malignancies of lung and esophagus

NASA Astrophysics Data System (ADS)

Sokolov, Victor V.; Chissov, Valery I.; Trakhtenberg, A. K.; Mamontov, A. S.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Gladunov, V. K.; Belous, T. A.; Aristarkhova, E. I.; Zharkova, Natalia N.; Smirnov, V. V.; Kozlov, Dmitrij N.

1996-01-01

In this paper the results of fluorescence diagnostics and photodynamic therapy of early stage malignancies of lung (17 patients) and esophagus (8 patients) are presented. 13 patients had multiple primary tumors. As photosensitizers the new drugs Photoheme and Photosense were used. Complete remission was obtained in 92%. The patients are followed up without relapses to 2,5 years.

Lung transplantation

PubMed Central

Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

2015-01-01

ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

Development of the Life Story in Early Adolescence

ERIC Educational Resources Information Center

Steiner, Kristina L.; Pillemer, David B.

2018-01-01

Life span developmental psychology proposes that the ability to create a coherent life narrative does not develop until early adolescence. Using a novel methodology, 10-, 12-, and 14-year-old participants were asked to tell their life stories aloud to a researcher. Later, participants separated their transcribed narratives into self-identified…

Early-life Origins of Lifecycle Well-being: Research and Policy Implications

PubMed Central

Currie, Janet; Rossin-Slater, Maya

2016-01-01

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the lifecycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the lifecycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socio-economic status. However, there is some variation in the degree to which current policies in the U.S. are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited. PMID:25558491

The habitat and nature of early life.

PubMed

Nisbet, E G; Sleep, N H

2001-02-22

Earth is over 4,500 million years old. Massive bombardment of the planet took place for the first 500-700 million years, and the largest impacts would have been capable of sterilizing the planet. Probably until 4,000 million years ago or later, occasional impacts might have heated the ocean over 100 degrees C. Life on Earth dates from before about 3,800 million years ago, and is likely to have gone through one or more hot-ocean 'bottlenecks'. Only hyperthermophiles (organisms optimally living in water at 80-110 degrees C) would have survived. It is possible that early life diversified near hydrothermal vents, but hypotheses that life first occupied other pre-bottleneck habitats are tenable (including transfer from Mars on ejecta from impacts there). Early hyperthermophile life, probably near hydrothermal systems, may have been non-photosynthetic, and many housekeeping proteins and biochemical processes may have an original hydrothermal heritage. The development of anoxygenic and then oxygenic photosynthesis would have allowed life to escape the hydrothermal setting. By about 3,500 million years ago, most of the principal biochemical pathways that sustain the modern biosphere had evolved, and were global in scope.

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Stenehjem, David D; Bellows, Brandon K; Yager, Kraig M; Jones, Joshua; Kaldate, Rajesh; Siebert, Uwe; Brixner, Diana I

2016-02-01

A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and

Pediatric lung transplantation

PubMed Central

2017-01-01

Pediatric lung transplantation has been undertaken since the 1980s, and it is today considered an accepted therapy option in carefully selected children with end-stage pulmonary diseases, providing carefully selected children a net survival benefit and improved health-related quality of life. Nowadays, >100 pediatric lung transplants are done worldwide every year. Here, specific pediatric aspects of lung transplantation are reviewed such as the surgical challenge, effects of immunosuppression on the developing pediatric immune system, and typical infections of childhood, as it is vital to comprehend that children undergoing lung transplants present a real challenge as children are not ‘just small adults’. Further, an update on the management of the pediatric lung transplant patient is provided in this review, and future challenges outlined. Indications for lung transplantation in children are different compared to adults, the most common being cystic fibrosis (CF). However, the primary diagnoses leading to pediatric lung transplantation vary considerably by age group. Furthermore, there are regional differences regarding the primary indication for lung transplantation in children. Overall, early referral, careful patient selection and appropriate timing of listing are crucial to achieve real survival benefit. Although allograft function is to be preserved, immunosuppressant-related side effects are common in children post-transplantation. Strategies need to be put into practice to reduce drug-related side effects through careful therapeutic drug monitoring and lowering of target levels of immunosuppression, to avoid acute-reversible and chronic-irreversible renal damage. Instead of a “one fits all approach”, tailored immunosuppression and a personalized therapy is to be advocated, particularly in children. Further, infectious complications are a common in children of all ages, accounting for almost 50% of death in the first year post

Outcomes of lung transplantation in patients with scleroderma.

PubMed

Massad, Malek G; Powell, Charles R; Kpodonu, Jacques; Tshibaka, Cimenga; Hanhan, Ziad; Snow, Norman J; Geha, Alexander S

2005-11-01

Patients with pulmonary insufficiency due to scleroderma have long been considered suboptimal candidates for lung transplantation. This has been supported by small single-center experiences that did not reflect the entire U.S. experience. We sought to evaluate the outcome of patients with scleroderma who underwent lung transplantation. We conducted a retrospective review of 47 patients with scleroderma who underwent lung transplantation at 23 U.S. centers between 1987 and 2004 and were reported to the United Network for Organ Sharing. Women constituted 57% of the patients. The mean age was 46 years. Twenty-seven patients received single lung transplants (57%), and the remaining received double lung transplants. The mean cold ischemia time was 4.1 hours. There were 7 early deaths (< or =30 days) and 17 late deaths (> 30 days). The causes of early death were primary graft failure and a cardiac event in two patients each and bacterial infection and stroke in one patient each. Late mortality was due to infection in seven patients, respiratory failure in three, malignancy in two, and multisystem organ failure, rejection, pulmonary hypertension, and a cardiac event in one patient each. The causes of early and late death were not recorded for two patients. One patient received a second transplant owing to graft failure of the first. Twenty-three patients (49%) were alive at a mean follow-up of 24 months. The Kaplan-Meier 1- and 3-year survival rates were 67.6% and 45.9% respectively, which are not significantly different from those of 10,070 patients given transplants for other lung conditions during the same period (75.5% and 58.8% respectively, P = 0.25). Donor gender, recipient's age, and type of transplant did not affect survival. In carefully selected patients with scleroderma who have end-stage lung disease, lung transplantation is a valid life-saving therapeutic option. Available data suggest acceptable short-term morbidity and mortality and a long-term survival

Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

PubMed Central

Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

2014-01-01

Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

Psychological distress and quality of life in lung cancer: the role of health-related stigma, illness appraisals and social constraints.

PubMed

Chambers, Suzanne K; Baade, Peter; Youl, Philippa; Aitken, Joanne; Occhipinti, Stefano; Vinod, Shalini; Valery, Patricia C; Garvey, Gail; Fong, Kwun M; Ball, David; Zorbas, Helen; Dunn, Jeff; O'Connell, Dianne L

2015-11-01

Health-related stigma is associated with negative psychological and quality of life outcomes in lung cancer patients. This study describes the impact of stigma on lung cancer patients' psychological distress and quality of life and explores the role of social constraints and illness appraisal as mediators of effect. A self-administered cross-sectional survey examined psychological distress and quality of life in 151 people (59% response rate) diagnosed with lung cancer from Queensland and New South Wales. Health-related stigma, social constraints and illness appraisals were assessed as predictors of adjustment outcomes. Forty-nine percent of patients reported elevated anxiety; 41% were depressed; and 51% had high global distress. Health-related stigma was significantly related to global psychological distress and quality of life with greater stigma and shame related to poorer outcomes. These effects were mediated by illness appraisals and social constraints. Health-related stigma appears to contribute to poorer adjustment by constraining interpersonal discussions about cancer and heightening feelings of threat. There is a need for the development and evaluation of interventions to ameliorate the negative effects of health-related stigma among lung cancer patients. © 2015 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

The positive and negative consequences of stressors during early life.

PubMed

Monaghan, Pat; Haussmann, Mark F

2015-11-01

We discuss the long-term effects of stress exposure in pre- and early postnal life. We present an evolutionary framework within which such effects can be viewed, and describe how the outcomes might vary with species life histories. We focus on stressors that induce increases in glucocorticoid hormones and discuss the advantages of an experimental approach. We describe a number of studies demonstrating how exposure to these hormones in early life can influence stress responsiveness and have substantial long-term, negative consequences for adult longevity. We also describe how early life exposure to mild levels of stressors can have beneficial effects on resilience to stress in later life, and discuss how the balance of costs and benefits is likely dependent on the nature of the adult environment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Identification of urine protein biomarkers with the potential for early detection of lung cancer.

PubMed

Zhang, Hongjuan; Cao, Jing; Li, Lin; Liu, Yanbin; Zhao, Hong; Li, Nan; Li, Bo; Zhang, Aiqun; Huang, Huanwei; Chen, She; Dong, Mengqiu; Yu, Lei; Zhang, Jian; Chen, Liang

2015-07-02

Lung cancer is the leading cause of cancer-related deaths and has an overall 5-year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low-dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer.

Does awareness of diagnosis influence health related quality of life in north Indian patients with lung cancer ?

PubMed

Aggarwal, Ashutosh Nath; Singh, Navneet; Gupta, Dheeraj; Behera, Digambar

2016-05-01

Several patients with cancer in India are not aware of their diagnosis. We evaluated the impact of awareness of cancer diagnosis on health-related quality of life (HRQL) in newly diagnosed patients with lung cancer. A total of 391 treatment-naïve patients with lung cancer, seen at the Lung Cancer Clinic of a tertiary care hospital in north India, were categorized into those aware of their diagnosis (group A) and those not aware (group B). All patients answered Hindi versions of abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-Bref) and European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), and its lung cancer module, EORTC QLQ-LC13. Various domain scores were computed and compared between the two groups. Analysis of covariance was used to determine significance of differences after adjustment for potential confounding factors. Only 117 (29.9%) patients were aware of their diagnosis. Of all, 302 (77.2%) patients had non-small cell lung cancer, and 301 (77.0%) had advanced disease. All HRQL domain scores were similar between the two groups, except that group B patients had significantly poorer median (interquartile range) Physical [39.3 (28.6-50.0) vs 46.4 (28.6-57.1)] and Environment [46.9 (40.6-56.3) vs 53.1 (0.6-65.6)] domain scores of WHOQOL-Bref, and p0 hysical function [60.0 (40.0-73.3) vs 66.7 (46.7-80.0)] and Fatigue [66.7 (55.6-77.8) vs 66.7 (44.4-66.7)] scores of QLQ-C30. After adjusting for gender, age, education, family income, and tumour extent, these differences were not significant. Disclosure of cancer diagnosis, or lack of it, had no significant impact on HRQL in patients with lung cancer after adjustment of potential confounders.

Palliative care consultation, quality-of-life measurements, and bereavement for end-of-life care in patients with lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).

PubMed

Griffin, John P; Koch, Kathryn A; Nelson, Judith E; Cooley, Mary E

2007-09-01

To develop clinical practice guidelines for application of palliative care consultation, quality-of-life measurements, and appropriate bereavement activities for patients with lung cancer. To review the pertinent medical literature on palliative care consultation, quality-of-life measurements, and bereavement for patients with lung cancer, developing multidisciplinary discussions with authorities in these areas, and evolving written guidelines for end-of-life care of these patients. Palliative care consultation has developed into a new specialty with credentialing of experts in this field based on extensive experience with patients in end-of-life circumstances including those with lung cancer. Bereavement studies of the physical and emotional morbidity of family members and caregivers before, during, and after the death of a cancer patient have supported truthful communication, consideration of psychological problems, effective palliative care, understanding of the patient's spiritual and cultural background, and sufficient forewarning of impending death. Multidisciplinary investigations and experiences, with emphasis on consultation and delivery of palliative care, timely use of quality-of-life measurements for morbidities of treatment modalities and prognosis, and an understanding of the multifaceted complexities of the bereavement process, have clarified additional responsibilities of the attending physician.

The effects of illness beliefs and chemotherapy impact on quality of life in Japanese and Dutch patients with breast or lung cancer.

PubMed

van der Kloot, Willem A; Uchida, Yuka; Inoue, Kenichi; Kobayashi, Kunihiko; Yamaoka, Kazue; Nortier, Hans W R; Kaptein, Ad A

2016-02-01

Responses to diagnosis and treatment of cancer are mediated by a patient's illness perceptions. Such perceptions, though different among individuals, may be culturally dependent, and act upon health related quality of life (HRQOL). Over time, individual patients show different types of response trajectories. Four issues were investigated: (I) country and disease differences in illness beliefs between Japanese and Dutch patients with lung or breast cancer; (II) country and disease differences in HRQOL in early chemotherapy; (III) individual, country, and disease differences among HRQOL trajectories; (IV) the impact of illness beliefs on HRQOL trajectories. A total of 89 Japanese and Dutch patients with lung or breast cancer cooperated immediately before, one week after, and eight weeks after the start of chemotherapy. Data included the EORTC QLQ-C30 quality of life (QL) questionnaire and the Brief Illness Perception Questionnaire (B-IPQ). EORTC QLQ-C30 scales were summarized by two dimensions: generalized quality of life (GENQOL) and psychological well-being (PSYQOL). (I) Japanese patients had higher means on B-IPQ's concern and time line than Dutch patients. Japanese lung cancer patients had a higher mean on treatment control than all other patients; (II) no differences between country and cancer type occurred on the two HRQOL dimensions. First assessment HRQOL differed significantly from the second and third assessments without differences between the latter two. Between the first two assessments, a decrease in GENQOL occurred, together with an improvement in PSYQOL; (III) individual differences dominated the trajectories; (IV) negative beliefs usually coincided with lower scores on GENQOL and PSYQOL. Patients initially lower on PSYQOL generally showed larger improvement. Individual differences in HRQOL dominate differences between culture and cancer type, and illness beliefs influence HRQOL changes in individual patients. Clinical application is possible through

Does early tetralogy of Fallot total correction give better final lung volumes?

PubMed

Sadeghi, Hasan Allah; Miri, Seyed Reza; Bakhshandeh, Hooman; Mirmesdagh, Yalda; Paziraee, Nazita

2013-06-01

Pulmonary blood flow may affect lung development in adulthood. Early total correction of tetralogy of Fallot may affect development of final lung volumes. We evaluated the effect of age at total correction on lung volumes years after the operation. In a retrospective cohort study on patients with totally corrected tetralogy of Fallot (mean age, 13.40 years at the time of follow-up), forced vital capacity, slow vital capacity, forced expiratory volume in 1 s, and other parameters were measured 154.8 ± 46.25 months after the operation. Comparison were made of 3 groups: ≤2-, 2-8-, and >8-years old at the time of total correction surgery. Among 322 enrolled patients, the mean values of the follow-up spirometry results in ≤2-, 2-8-, >8-year-olds and the percentage of predicted values were respectively: vital capacity: 4.46 ± 0.57 L (107% ± 10.96%), 3.89 ± 0.58 L (91.10% ± 12.25%), 3.25 ± 0.48 L (82.35% ± 10.62%), p < 0.001; forced vital capacity: 4.28 ± 0.63 L (95.90% ± 18.77%), 3.76 ± 0.58 L (90.83% ± 12.52%), 3.14 ± 0.49 L (83.26% ± 11.71%), p < 0.001; forced expiratory volume in 1 s: 4.22 ± 0.63 L (104.84% ± 13.64%), 3.66 ± 0.58 L (90.61% ± 12.59%), 3.02 ± 0.48 L (84.31% ± 12%), p < 0.001. Early correction of defects or reestablishments of perfusion of tetralogy of Fallot before completion of lung development might improve final adulthood lung volumes and capacities. It is better to consider total correction for all tetralogy of Fallot patients below 2-years old, or at least below 8-years old, if it is technically possible.

Lung Focused Resuscitation at a Specialized Donor Care Facility Improves Lung Procurement Rates.

PubMed

Chang, Stephanie H; Kreisel, Daniel; Marklin, Gary F; Cook, Lindsey; Hachem, Ramsey; Kozower, Benjamin D; Balsara, Keki R; Bell, Jennifer M; Frederiksen, Christine; Meyers, Bryan F; Patterson, G Alexander; Puri, Varun

2018-05-01

Lung procurement for transplantation occurs in approximately 20% of brain dead donors and is a major impediment to wider application of lung transplantation. We investigated the effect of lung protective management at a specialized donor care facility on lung procurement rates from brain dead donors. Our local organ procurement organization instituted a protocol of lung protective management at a freestanding specialized donor care facility in 2008. Brain dead donors from 2001 to 2007 (early period) were compared with those from 2009 to 2016 (current period) for lung procurement rates and other solid-organ procurement rates using a prospectively maintained database. An overall increase occurred in the number of brain dead donors during the study period (early group, 791; late group, 1,333; p < 0.0001). The lung procurement rate (lung donors/all brain dead donors) improved markedly after the introduction of lung protective management (early group, 157 of 791 [19.8%]; current group, 452 of 1,333 [33.9%]; p < 0.0001). The overall organ procurement rate (total number of organs procured/donor) also increased during the study period (early group, 3.5 organs/donor; current group, 3.8 organs/donor; p = 0.006). Lung protective management in brain dead donors at a specialized donor care facility is associated with higher lung utilization rates compared with conventional management. This strategy does not adversely affect the utilization of other organs in a multiorgan donor. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Precedents of perceived social support: personality and early life experiences.

PubMed

Kitamura, T; Kijima, N; Watanabe, K; Takezaki, Y; Tanaka, E

1999-12-01

In order to examine the effects of personality and early life experiences on perceived social support, a total of 97 young Japanese women were investigated. Current interpersonal relationships were measured by an interview modified from Henderson et al.'s Interview Schedule for Social Interaction (ISSI). Personality was measured by Cloninger et al.'s Temperament and Character Inventory. Early life experiences at home and outside of home were also identified in the interview. The number of sources of perceived support was correlated with self-directness, while satisfaction with perceived support was correlated with novelty seeking and with low harm avoidance. No early life experiences--early loss of a parent, perceived parenting, childhood abuse experiences, experiences of being bullied and/or other life events--showed significant correlations with the number or satisfaction of supportive people. The quantity and quality of perception of social support differ in their link to personality, and perceived social support may, to some extent, be explainable in terms of personality.

Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.

PubMed

Snowdon, D A; Kemper, S J; Mortimer, J A; Greiner, L H; Wekstein, D R; Markesbery, W R

1996-02-21

To determine if linguistic ability in early life is associated with cognitive function and Alzheimer's disease in late life. Two measures of linguistic ability in early life, idea density and grammatical complexity, were derived from autobiographies written at a mean age of 22 years. Approximately 58 years later, the women who wrote these autobiographies participated in an assessment of cognitive function, and those who subsequently died were evaluated neuropathologically. Convents in the United States participating in the Nun Study; primarily convents in the Milwaukee, Wis, area. Cognitive function was investigated in 93 participants who were aged 75 to 95 years at the time of their assessments, and Alzheimer's disease was investigated in the 14 participants who died at 79 to 96 years of age. Seven neuropsychological tests and neuropathologically confirmed Alzheimer's disease. Low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Low idea density in early life had stronger and more consistent associations with poor cognitive function than did low grammatical complexity. Among the 14 sisters who died, neuropathologically confirmed Alzheimer's disease was present in all of those with low idea density in early life and in none of those with high idea density. Low linguistic ability in early life was a strong predictor of poor cognitive function and Alzheimer's disease in late life.

Overstating the evidence for lung cancer screening: the International Early Lung Cancer Action Program (I-ELCAP) study.

PubMed

Welch, H Gilbert; Woloshin, Steven; Schwartz, Lisa M; Gordis, Leon; Gøtzsche, Peter C; Harris, Russell; Kramer, Barnett S; Ransohoff, David F

2007-11-26

Last year, the New England Journal of Medicine ran a lead article reporting that patients with lung cancer had a 10-year survival approaching 90% if detected by screening spiral computed tomography. The publication garnered considerable media attention, and some felt that its findings provided a persuasive case for the immediate initiation of lung cancer screening. We strongly disagree. In this article, we highlight 4 reasons why the publication does not make a persuasive case for screening: the study had no control group, it lacked an unbiased outcome measure, it did not consider what is already known about this topic from previous studies, and it did not address the harms of screening. We conclude with 2 fundamental principles that physicians should remember when thinking about screening: (1) survival is always prolonged by early detection, even when deaths are not delayed nor any lives saved, and (2) randomized trials are the only way to reliably determine whether screening does more good than harm.

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions.

PubMed

Stauder, Michael C; Macdonald, O Kenneth; Olivier, Kenneth R; Call, Jason A; Lafata, Kyle; Mayo, Charles S; Miller, Robert C; Brown, Paul D; Bauer, Heather J; Garces, Yolanda I

2011-05-01

Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2016-09-01

Radiotherapy ( SABR ) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W. Loo, Jr., M.D., Ph.D CONTRACTING ORGANIZATION: Leland Stanford Junior University...CONTRACT NUMBER W81XWH-12-1-0236 Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer 5b. GRANT NUMBER 5c. PROGRAM...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Purpose and scope: Stereotactic ablative radiotherapy ( SABR ) has become a new standard

Early-Life Nutritional Programming of Health and Disease in The Gambia.

PubMed

Moore, Sophie E

2017-01-01

Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality. © 2017 S. Karger AG, Basel.

Early-life gut microbiome and egg allergy.

PubMed

Fazlollahi, M; Chun, Y; Grishin, A; Wood, R A; Burks, A W; Dawson, P; Jones, S M; Leung, D Y M; Sampson, H A; Sicherer, S H; Bunyavanich, S

2018-07-01

Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10 -4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis P adj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10 -4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Differential effects of early palliative care based on the age and sex of patients with advanced cancer from a randomized controlled trial.

PubMed

Nipp, Ryan D; El-Jawahri, Areej; Traeger, Lara; Jacobs, Jamie M; Gallagher, Emily R; Park, Elyse R; Jackson, Vicki A; Pirl, William F; Temel, Jennifer S; Greer, Joseph A

2018-04-01

Early palliative care interventions enhance patient outcomes, including quality of life, mood, and coping, but it remains unclear whether certain subgroups of patients are more likely to benefit from early palliative care. We explored whether age and sex moderate the improved outcomes seen with early palliative care. We performed a secondary analysis of data from a randomized trial of 350 patients with advanced lung and non-colorectal gastrointestinal cancer. Patients received an early palliative care intervention integrated with oncology care or usual oncology care alone. We used linear regression to determine if age (older or younger than 65) and sex moderated the effects of the intervention on quality of life (Functional Assessment of Cancer Therapy-General (FACT-G)), depression symptoms (Patient Health Questionnaire 9 (PHQ-9)), and coping (Brief COPE) within lung and gastrointestinal subgroups. At 24 weeks, younger patients with lung cancer receiving early palliative care reported increased use of active coping ( B = 1.74; p = 0.02) and decreased use of avoidant coping ( B = -0.97; p = 0.02), but the effects of early palliative care on these outcomes were not significant for older patients. Male patients with lung cancer assigned to early palliative care reported better quality of life (FACT-G: B = 9.31; p = 0.01) and lower depression scores (PHQ-9: B = -2.82; p = 0.02), but the effects of early palliative care on these outcomes were not significant for female patients. At 24 weeks, we found no age or sex moderation effects within the gastrointestinal cancer subgroup. Age and sex moderate the effects of early palliative care for patients with advanced lung cancer. Early palliative care may need to be tailored to individuals' unique sociodemographic and clinical characteristics.

Does living near heavy industry cause lung cancer in women? A case-control study using life grid interviews.

PubMed

Edwards, R; Pless-Mulloli, T; Howel, D; Chadwick, T; Bhopal, R; Harrison, R; Gribbin, H

2006-12-01

The incidence of lung cancer among women is high in the highly industrialised area of Teesside in north-east England. Previous research has implicated industrial pollution as a possible cause. A study was undertaken to investigate whether prolonged residence close to heavy industry is associated with lung cancer among women in Teesside. Two hundred and four women aged <80 years with incident primary lung cancer and 339 age matched community controls were recruited to a population based case-control study. Life course residential, occupational, and active and passive smoking histories were obtained using an interviewer administered questionnaire. The age adjusted odds ratio (OR) for lung cancer among people living >25 years v 0 years near (within 0-5 km) heavy industry in Teesside was 2.13 (95% CI 1.34 to 3.38). After adjustment for confounding factors the OR was 1.83 (95% CI 0.82 to 4.08) for >25 years or 1.10 (95% CI 0.96 to 1.26) for an additional 10 years living near industry. ORs were similar after residence near heavy industry outside Teesside was also included, and when latency was allowed for by disregarding residential exposures within the last 20 years. Adjustment for active smoking had the greatest effect on the OR. This population based study using life grid interviews for life course exposure assessment has addressed many deficiencies in the design of previous studies. The findings support those in most of the international literature of a modestly raised risk of lung cancer with prolonged residence close to heavy industry, although the confidence intervals were wide. The effect of air pollution on the incidence of lung cancer merits continued study.

Early life factors in the pathogenesis of osteoporosis.

PubMed

Winsloe, Chivon; Earl, Susie; Dennison, Elaine M; Cooper, Cyrus; Harvey, Nicholas C

2009-12-01

Osteoporosis is a major public health burden through associated fragility fractures. Bone mass, a composite of bone size and volumetric density, increases through early life and childhood to a peak in early adulthood. The peak bone mass attained is a strong predictor of future risk of osteoporosis. Evidence is accruing that environmental factors in utero and in early infancy may permanently modify the postnatal pattern of skeletal growth to peak and thus influence risk of osteoporosis in later life. This article describes the latest data in this exciting area of research, including novel epigenetic and translation work, which should help to elucidate the underlying mechanisms and give rise to potential public health interventions to reduce the burden of osteoporotic fracture in future generations.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

Early life influences on cognitive impairment among oldest old Chinese.

PubMed

Zhang, Zhenmei; Gu, Danan; Hayward, Mark D

2008-01-01

This article examines the effects of early life socioeconomic conditions on the risk of cognitive impairment among oldest old persons in China. We also examine whether adult socioeconomic status mediates the association between early life socioeconomic status and cognitive impairment in old age. Data derived from two waves (1998-2000) of the Chinese Longitudinal Healthy Longevity Survey. We estimated logistic and multinomial regression models of cognitive impairment for a nationwide sample of people aged 80 to 105 (N = 8,444). Among both men and women, urban residence in early life as well as education was associated with lower odds of cognitive impairment at baseline. We found modest support for a protective effect of advantaged childhood background on the odds of cognitive impairment onset during the 2-year follow-up, especially among women. Our findings suggest that socioeconomic environment throughout the life course, early life in particular, can influence the risk of cognitive impairment in old age. Not only can public policy that targets illiteracy, hunger, and poverty improve the lives of tens of thousands of children, but ultimately such investments will pay significant dividends many decades later in enhancing the cognitive well-being of older persons.

Detection of early changes in lung cell cytology by flow-systems analysis techniques, July 1--December 31, 1975

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinkamp, J.A.; Ingram, M.; Hansen, K.M.

1976-03-01

This report summarizes results of preliminary experiments to demonstrate the feasibility of using automated flow-systems analysis in detecting early changes of respiratory epithelium exposed to physical and chemical agents associated with the by-products of nonnuclear energy production. The Syrian hamster was selected as the experimental test animal to begin investigation of the effects of toxic agents to cells of the respiratory tract. Since initiation of the program approximately six months ago, the goals have been acquisition of adequate numbers of exfoliated cells from the lung; adaptation of cytological techniques developed on human exfoliated gynecological samples to hamster lung epithelium formore » obtaining single-cell suspensions; utilization of existing cell staining methods to measure DNA content in lung cells; and analysis of DNA content and cell size. As the flow-system cell analysis technology is adapted to the measurement of exfoliated lung cells, rapid and quantitative determination of early changes in the physical and biochemical cellular properties will be attempted as a function of exposure to the toxic agents. (auth)« less

The OBELIX project: early life exposure to endocrine disruptors and obesity.

PubMed

Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

2011-12-01

The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

Mortality inequality in populations with equal life expectancy: Arriaga's decomposition method in SAS, Stata, and Excel.

PubMed

Auger, Nathalie; Feuillet, Pascaline; Martel, Sylvie; Lo, Ernest; Barry, Amadou D; Harper, Sam

2014-08-01

Life expectancy is used to measure population health, but large differences in mortality can be masked even when there is no life expectancy gap. We demonstrate how Arriaga's decomposition method can be used to assess inequality in mortality between populations with near equal life expectancy. We calculated life expectancy at birth for Quebec and the rest of Canada from 2005 to 2009 using life tables and partitioned the gap between both populations into age and cause-specific components using Arriaga's method. The life expectancy gap between Quebec and Canada was negligible (<0.1 years). Decomposition of the gap showed that higher lung cancer mortality in Quebec was offset by cardiovascular mortality in the rest of Canada, resulting in identical life expectancy in both groups. Lung cancer in Quebec had a greater impact at early ages, whereas cardiovascular mortality in Canada had a greater impact at older ages. Despite the absence of a gap, we demonstrate using decomposition analyses how lung cancer at early ages lowered life expectancy in Quebec, whereas cardiovascular causes at older ages lowered life expectancy in Canada. We provide SAS/Stata code and an Excel spreadsheeet to facilitate application of Arriaga's method to other settings. Copyright © 2014 Elsevier Inc. All rights reserved.

Early Life on Earth: the Ancient Fossil Record

NASA Astrophysics Data System (ADS)

Westall, F.

2004-07-01

The evidence for early life and its initial evolution on Earth is lin= ked intimately with the geological evolution of the early Earth. The environment of the early Earth would be considered extreme by modern standards: hot (50-80=B0C), volcanically and hydrothermally active, a= noxic, high UV flux, and a high flux of extraterrestrial impacts. Habitats = for life were more limited until continent-building processes resulted in= the formation of stable cratons with wide, shallow, continental platforms= in the Mid-Late Archaean. Unfortunately there are no records of the first appearance of life and the earliest isotopic indications of the exist= ence of organisms fractionating carbon in ~3.8 Ga rocks from the Isua greenst= one belt in Greenland are tenuous. Well-preserved microfossils and micro= bial mats (in the form of tabular and domical stromatolites) occur in 3.5-= 3.3 Ga, Early Archaean, sedimentary formations from the Barberton (South Afri= ca) and Pilbara (Australia) greenstone belts. They document life forms that = show a relatively advanced level of evolution. Microfossil morphology inclu= des filamentous, coccoid, rod and vibroid shapes. Colonial microorganism= s formed biofilms and microbial mats at the surfaces of volcaniclastic = and chemical sediments, some of which created (small) macroscopic microbi= alites such as stromatolites. Anoxygenic photosynthesis may already have developed. Carbon, nitrogen and sulphur isotopes ratios are in the r= ange of those for organisms with anaerobic metabolisms, such as methanogenesi= s, sulphate reduction and photosynthesis. Life was apparently distribute= d widely in shallow-water to littoral environments, including exposed, evaporitic basins and regions of hydrothermal activity. Biomass in t= he early Archaean was restricted owing to the limited amount of energy t= hat could be produced by anaerobic metabolisms. Microfossils resembling o= xygenic photosynthesisers, such as cyanobacteria, probably first occurred in

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paul, Jijo; Yang, Cungeng; Wu, Hui

Purpose: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Methods and Materials: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from themore » daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. Results: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R{sup 2} > 0.99) and correlates weakly with the change in GTV (R{sup 2} = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Conclusion: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.« less

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography.

PubMed

Paul, Jijo; Yang, Cungeng; Wu, Hui; Tai, An; Dalah, Entesar; Zheng, Cheng; Johnstone, Candice; Kong, Feng-Ming; Gore, Elizabeth; Li, X Allen

2017-06-01

To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R 2  > 0.99) and correlates weakly with the change in GTV (R 2  = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Isolated lung transplantation for end-stage lung disease: a viable therapy.

PubMed

Egan, T M; Westerman, J H; Lambert, C J; Detterbeck, F C; Thompson, J T; Mill, M R; Keagy, B A; Paradowski, L J; Wilcox, B R

1992-04-01

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5

Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

NASA Astrophysics Data System (ADS)

Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

2012-02-01

Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study.

PubMed

Riley, Kathryn P; Snowdon, David A; Desrosiers, Mark F; Markesbery, William R

2005-03-01

The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.

Early life stress paradigms in rodents: potential animal models of depression?

PubMed

Schmidt, Mathias V; Wang, Xiao-Dong; Meijer, Onno C

2011-03-01

While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents. Based on human etiology, the assumption has been made that depression-like behavior in rats and mice can be modulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life. Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes. Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments. We have also included a small number of stress-related pharmacological models. We find that for most early life paradigms per se, the actual validity for depression is limited. A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors. Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges.

Long-term failure of alveologenesis after an early short-term exposure to a PDGF-receptor antagonist.

PubMed

Lau, Mandy; Masood, Azhar; Yi, Man; Belcastro, Rosetta; Li, Jun; Tanswell, A Keith

2011-04-01

Survivors of moderate-to-severe bronchopulmonary dysplasia have impaired alveologenesis lasting at least into early adult life. The mechanisms underlying this long-term effect are unknown. We hypothesized that short-term inhibition of growth factor-mediated early alveolar formation would result in a long-term impairment of subsequent alveologenesis. Neonatal rats were injected daily with the platelet-derived growth factor (PDGF) receptor antagonist, imatinib mesylate, from day 1-7 of life, to inhibit the early alveolar formation occurring by in-growth of secondary crests into precursor saccules. The pups were then allowed to recover for 7, 14, 21, or 58 days. In imatinib-treated pups, DNA synthesis in total lung cells, and specifically in cells of secondary crests, was reduced at day 8 of life, had rebounded on day 14 of life but was then again reduced by day 28 of life. At day 8 of life, imatinib-treated pups had impaired alveologenesis as reflected by a decrease in secondary crests, an increase in alveolar size, and an overall decrease in both estimated alveolar number and generations compared with age-matched controls. No meaningful recovery was observed, even after a 21- or 58-day recovery period. The lungs of imatinib-treated pups had increased fibulin-5 content and an abnormal deposition of elastin. We conclude that reduced signaling through the PDGF pathways, at an early stage of alveologenesis, can result in long-lasting changes in lung architecture. A likely mechanism is through impaired formation of the elastin scaffold required for alveolarization.

Technology and outcomes assessment in lung transplantation.

PubMed

Yusen, Roger D

2009-01-15

Lung transplantation offers the hope of prolonged survival and significant improvement in quality of life to patients that have advanced lung diseases. However, the medical literature lacks strong positive evidence and shows conflicting information regarding survival and quality of life outcomes related to lung transplantation. Decisions about the use of lung transplantation require an assessment of trade-offs: do the potential health and quality of life benefits outweigh the potential risks and harms? No amount of theoretical reasoning can resolve this question; empiric data are needed. Rational analyses of these trade-offs require valid measurements of the benefits and harms to the patients in all relevant domains that affect survival and quality of life. Lung transplant systems and registries mainly focus outcomes assessment on patient survival on the waiting list and after transplantation. Improved analytic approaches allow comparisons of the survival effects of lung transplantation versus continued waiting. Lung transplant entities do not routinely collect quality of life data. However, the medical community and the public want to know how lung transplantation affects quality of life. Given the huge stakes for the patients, the providers, and the healthcare systems, key stakeholders need to further support quality of life assessment in patients with advanced lung disease that enter into the lung transplant systems. Studies of lung transplantation and its related technologies should assess patients with tools that integrate both survival and quality of life information. Higher quality information obtained will lead to improved knowledge and more informed decision making.

New insights into a hot environment for early life.

PubMed

Dai, Jianghong

2017-06-01

Investigating the physical-chemical setting of early life is a challenging task. In this contribution, the author attempted to introduce a provocative concept from cosmology - cosmic microwave background (CMB), which is the residual thermal radiation from a hot early Universe - to the field. For this purpose, the author revisited a recently deduced biomarker, the 1,6-anhydro bond of sugars in bacteria. In vitro, the 1,6-anhydro bond of sugars reflects and captures residual thermal radiation in thermochemical processes and therefore is somewhat analogous to CMB. In vivo, the formation process of the 1,6-anhydro bond of sugars on the peptidoglycan of prokaryotic cell wall is parallel to in vitro processes, suggesting that the 1,6-anhydro bond is an ideal CMB-like analogue that suggests a hot setting for early life. The CMB-like 1,6-anhydro bond is involved in the life cycle of viruses and the metabolism of eukaryotes, underlying this notion. From a novel perspective, the application of the concept of the CMB to microbial ecology may give new insights into a hot environment, such as hydrothermal vents, supporting early life and providing hypotheses to test in molecular palaeontology. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Psychological distress and quality of life in lung cancer: the role of health‐related stigma, illness appraisals and social constraints

PubMed Central

Baade, Peter; Youl, Philippa; Aitken, Joanne; Occhipinti, Stefano; Vinod, Shalini; Valery, Patricia C.; Garvey, Gail; Fong, Kwun M.; Ball, David; Zorbas, Helen; Dunn, Jeff; O'Connell, Dianne L.

2015-01-01

Abstract Objective Health‐related stigma is associated with negative psychological and quality of life outcomes in lung cancer patients. This study describes the impact of stigma on lung cancer patients' psychological distress and quality of life and explores the role of social constraints and illness appraisal as mediators of effect. Methods A self‐administered cross‐sectional survey examined psychological distress and quality of life in 151 people (59% response rate) diagnosed with lung cancer from Queensland and New South Wales. Health‐related stigma, social constraints and illness appraisals were assessed as predictors of adjustment outcomes. Results Forty‐nine percent of patients reported elevated anxiety; 41% were depressed; and 51% had high global distress. Health‐related stigma was significantly related to global psychological distress and quality of life with greater stigma and shame related to poorer outcomes. These effects were mediated by illness appraisals and social constraints. Conclusions Health‐related stigma appears to contribute to poorer adjustment by constraining interpersonal discussions about cancer and heightening feelings of threat. There is a need for the development and evaluation of interventions to ameliorate the negative effects of health‐related stigma among lung cancer patients. © 2015 The Authors. Psycho‐Oncology Published by John Wiley & Sons Ltd. PMID:25920906

A week in the life of lung cancer survivors: Daily reports of stress, worry, mood, and symptoms.

PubMed

Aronson, Keith R; Wagstaff, David A; Farace, Elana; Muscat, Joshua; Belani, Chandra; Almokadem, Salah; Fossum, Thyra

2016-10-01

This study examined the day-to-day lives of early stage lung cancer survivors who were discharged from treatment between 2 and 24 months prior to the study. Lung cancer survivors were called on eight consecutive nights and completed an interview about their daily experiences. Repeated measures, multilevel analysis of the phone interview data was conducted. Survivors reported few daily stressor exposures or somatic symptoms. Daily moods were generally positive, and survivors reported living quite independently. Lung cancer survivors did not report experiencing health-related worry on a daily basis. The findings from this study create a much more positive picture of lung cancer survivorship relative to prior studies. © The Author(s) 2015.

Baby Boomers and Birth Certificates: Early-Life Socioeconomic Status and Cancer Risk in Adulthood.

PubMed

Stroup, Antoinette M; Herget, Kimberly A; Hanson, Heidi A; Reed, Diana Lane; Butler, Jared T; Henry, Kevin A; Harrell, C Janna; Sweeney, Carol; Smith, Ken R

2017-01-01

Early-life socioeconomic status (SES) may play a role in cancer risk in adulthood. However, measuring SES retrospectively presents challenges. Parental occupation on the birth certificate is a novel method of ascertaining early-life SES that has not been applied in cancer epidemiology. For a Baby-Boom cohort born from 1945-1959 in two Utah counties, individual-level Nam-Powers SES (Np-SES) was derived from parental industry/occupation reported on birth certificates. Neighborhood SES was estimated from average household income of census tract at birth. Cancer incidence was determined by linkage to Utah Cancer Registry records through the Utah Population Database. Hazard ratios (HR) for cancer risk by SES quartile were estimated using Cox proportional hazards regression. Females with low Np-SES at birth had lower risk of breast cancer compared with those in the highest Np-SES group [HR Q1/Q4 = 0.83; 95% confidence interval (CI), 0.72-0.97; HR Q2/Q4 = 0.81; 95% CI, 0.69-0.96]. Np-SES was inversely associated with melanoma (HR Q1/Q4 = 0.81; 95% CI, 0.67-0.98) and prostate cancer (HR Q1/Q4 = 0.70; 95% CI, 0.56-0.88). Women born into lower SES neighborhoods had significantly increased risk for invasive cervical cancer (HR Q1/Q4 = 1.44; 95% CI, 1.12-1.85; HR Q2/Q4 = 1.33; 95% CI, 1.04-1.72). Neighborhood SES had similar effects for melanoma and prostate cancers, but was not associated with female breast cancer. We found no association with SES for pancreas, lung, and colon and rectal cancers. Individual SES derived from parental occupation at birth was associated with altered risk for several cancer sites. This novel methodology can contribute to improved understanding of the role of early-life SES on cancer risk. Cancer Epidemiol Biomarkers Prev; 26(1); 75-84. ©2016 AACR. ©2016 American Association for Cancer Research.

Baby Boomers and Birth Certificates: Early Life Socioeconomic Status and Cancer Risk in Adulthood

PubMed Central

Stroup, Antoinette M.; Herget, Kimberly A; Hanson, Heidi A; Reed, Diana Lane; Butler, Jared T; Henry, Kevin A; Harrell, C Janna; Sweeney, Carol; Smith, Ken R

2016-01-01

BACKGROUND Early life socioeconomic status (SES) may play a role in cancer risk in adulthood. However, measuring SES retrospectively presents challenges. Parental occupation on the birth certificate is a novel method of ascertaining early-life SES that has not been applied in cancer epidemiology. METHODS For a Baby-Boom cohort born in 1945–1959 in two Utah counties, individual-level Nam-Powers SES (Np-SES) was derived from parental industry/occupation reported on birth certificates. Neighborhood SES was estimated from average household income of census tract at birth. Cancer incidence was determined by linkage to Utah Cancer Registry records through the Utah Population Database. Hazard ratios (HR) for cancer risk by SES quartile were estimated using Cox proportional hazards regression. RESULTS Females with low Np-SES at birth had lower risk of breast cancer compared to those in the highest Np-SES group (HRQ1/Q4=0.83 95% CI: 0.72–0.97; HRQ2/Q4=0.81 95% CI: 0.69–0.96). Np-SES was inversely associated with melanoma (HRQ1/Q4=0.81 95% CI: 0.67–0.98) and prostate cancer (HRQ1/Q4=0.70 95% CI: 0.56–0.88). Women born into lower SES neighborhoods had significantly increased risk for invasive cervical cancer (HRQ1/Q4=1.44 95% CI: 1.12–1.85; HRQ2/Q4=1.33 95% CI: 1.04–1.72). Neighborhood SES had similar effects for melanoma and prostate cancers, but was not associated with female breast cancer. We found no association with SES for pancreas, lung, and colon and rectal cancers. CONCLUSION Individual SES derived from parental occupation at birth was associated with altered risk for several cancer sites. IMPACT This novel methodology can contribute to improved understanding of the role of early-life SES in affecting cancer risk. PMID:27655898

Life satisfaction in early adolescence: personal, neighborhood, school, family, and peer influences.

PubMed

Oberle, Eva; Schonert-Reichl, Kimberly A; Zumbo, Bruno D

2011-07-01

Drawing from an ecological assets framework as well as research and theory on positive youth development, this study examined the relationship of early adolescents' satisfaction with life to trait optimism and assets representing the social contexts in which early adolescents spend most of their time. Self-reports of satisfaction with life, optimism, and ecological assets in the school (school connectedness), neighborhood (perceived neighborhood support), family (perceived parental support), and peer group (positive peer relationships) were assessed in a sample of 1,402 4th to 7th graders (47% female) from 25 public elementary schools. Multilevel modeling (MLM) was conducted to analyze the variability in life satisfaction both at the individual and the school level. As hypothesized, adding optimism and the dimensions representing the ecology of early adolescence to the model significantly reduced the variability in life satisfaction at both levels of analysis. Both personal (optimism) and all of the ecological assets significantly and positively predicted early adolescents' life satisfaction. The results suggest the theoretical and practical utility of an assets approach for understanding life satisfaction in early adolescence.

Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer

PubMed Central

Nawaz, Imran; Qiu, Xiaoming; Wu, Heng; Li, Yang; Fan, Yaguang; Hu, Li-Fu; Zhou, Qinghua; Ernberg, Ingemar

2014-01-01

Lung cancer is a worldwide health problem and a leading cause of cancer-related deaths. Silencing of potential tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event in the initiation and development of cancer. Thus, methylated cancer type-specific TSGs in DNA can serve as useful biomarkers for early cancer detection. We have now developed a “Multiplex Methylation Specific PCR” (MMSP) assay for analysis of the methylation status of multiple potential TSGs by a single PCR reaction. This method will be useful for early diagnosis and treatment outcome studies of non-small cell lung cancer (NSCLC). Genome-wide CpG methylation and expression microarrays were performed on lung cancer tissues and matched distant non-cancerous tissues from three NSCLC patients from China. Thirty-eight potential TSGs were selected and analyzed by methylation PCR on bisulfite treated DNA. On the basis of sensitivity and specificity, six marker genes, HOXA9, TBX5, PITX2, CALCA, RASSF1A, and DLEC1, were selected to establish the MMSP assay. This assay was then used to analyze lung cancer tissues and matched distant non-cancerous tissues from 70 patients with NSCLC, as well as 24 patients with benign pulmonary lesion as controls. The sensitivity of the assay was 99% (69/70). HOXA9 and TBX5 were the 2 most sensitive marker genes: 87% (61/70) and 84% (59/70), respectively. RASSF1A and DLEC1 showed the highest specificity at 99% (69/70). Using the criterion of identifying at least any two methylated marker genes, 61/70 cancer samples were positive, corresponding to a sensitivity of 87% and a specificity of 94%. Early stage I or II NSCLC could even be detected with a 100% specificity and 86% sensitivity. In conclusion, MMSP has the potential to be developed into a population-based screening tool and can be useful for early diagnosis of NSCLC. It might also be suitable for monitoring treatment outcome and recurrence. PMID:24937636

[Joint application of 7 interventional pulmonology methods in early diagnosis of lung cancer].

PubMed

Jin, Fa-Guang; Li, Wang-Ping; Mu, De-Guang; Chu, Dong-Ling; Fu, En-Qing; Xie, Yong-Hong; Lu, Jing-Li; Sun, Ya-Ni

2009-06-23

To evaluate the combination of 7 interventional pulmonology methods in early diagnosis of lung cancer. A total of 467 patients with thoracic and pulmonary lesions (include hilum pulmonis lymphadenectasis, mediastinal lymphadenectasis, pulmonary scobination, lump, lamellar infiltration, small amount of pleural fluid and pleural scobination) had negative results via exfoliative cytology, bacteriology and routine bronchoscopy. All these patients had ultrathin bronchoscopy with biopsy and brushing. For those 155 cases whose foci were located at porta pulmonis, inner zone or median zone, the authors applied ultrathin bronchoscopy with biopsy and brushing guided by X-ray. For those 95 cases whose foci were located at median zone or outer zone and unconnected with chest wall, per cutem lung puncture needle aspiration was employed under the guidance of X-ray. For those 102 cases whose foci were tightly connected with pleural membrane, per cutem lung puncture biopsy was employed under the guidance of type-B ultrasonic. For those 59 cases with suspected central airway foci, auto-fluorescence bronchoscopic biopsy and brushing were employed. For those 67 cases with hilum pulmonis or mediastinal lymphadenectasis, endobronchial ultrasonic transbronchial needle aspiration (EBUS-TBNA) was employed. For those 23 cases with small amount of pleural fluid or pleural scobination, electronic thoracoscopic biopsy and brushing were employed. It was found that 118 cases were diagnosed by ultrathin bronchoscopic biopsy and brushing with a positive rate of 25.3% (118/467), 105 cases by ultrathin bronchoscopy with biopsy and brushing guided by X-ray with a positive rate of 67.7% (105/155), 63 cases by per cutem lung puncture needle aspiration under the guidance of X-ray with a positive rate of 66.3% (63/95), 69 cases by per cutem lung puncture biopsy under the guidance of type-B ultrasound with a positive rate of 67.6% (69/102), 18 cases by auto-fluorescence bronchoscopic biopsy and brushing

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

Early Mars: A Warm Wet Niche for Life

NASA Technical Reports Server (NTRS)

Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.

2010-01-01

Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution had conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 Ma of Martian history were ripe for life to develop because of the abundance of: (i) Water-as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at approx.3.9 Ga, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic patterns in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 Ma?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve)

The composition of the gut microbiota throughout life, with an emphasis on early life

PubMed Central

Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine; Ross, R. Paul; Kober, Olivia I.; Juge, Nathalie; Avershina, Ekaterina; Rudi, Knut; Narbad, Arjan; Jenmalm, Maria C.; Marchesi, Julian R.; Collado, Maria Carmen

2015-01-01

The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health. PMID:25651996

Development of principles of two-cascaded laser speckle-microscopy with implication to high-precision express diagnostics of chlamydial infection

NASA Astrophysics Data System (ADS)

Ulianova, Onega; Moiseeva, Yulia; Filonova, Nadezhda; Subbotina, Irina; Zaitsev, Sergey; Saltykov, Yury; Polyanina, Tatiana; Lyapina, Anna; Ulyanov, Sergey; Larionova, Olga; Utz, Sergey; Feodorova, Valentina

2018-04-01

Principles of two-cascaded laser speckle-microscopy prospect for application to express diagnostics of chlamydial infection are developed. Prototype of two-cascaded speckle-microscope is designed and tested. Specific case of illumination of bacterial cells by dynamic speckles is considered. Express method of detection of epithelial cells, containing defects, which are caused by Chlamydia trachomatis bacteria, is suggested. Results of improved recognition of C. trachomatis bacteria are discussed.

Influence of early neurological complications on clinical outcome following lung transplant.

PubMed

Gamez, Josep; Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

2017-01-01

Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

Influence of early neurological complications on clinical outcome following lung transplant

PubMed Central

Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

2017-01-01

Background Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. Methods We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Results Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients’ survival. Conclusions The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors. PMID:28301586

Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats.

PubMed

Giraud, O; Seince, P F; Rolland, C; Leçon-Malas, V; Desmonts, J M; Aubier, M; Dehoux, M

2000-12-01

Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific

The die is cast - Arsenic exposure in early life and disease susceptibility

EPA Science Inventory

Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

Association of early- and adult-life socioeconomic circumstances with muscle strength in older age.

PubMed

Cheval, Boris; Boisgontier, Matthieu P; Orsholits, Dan; Sieber, Stefan; Guessous, Idris; Gabriel, Rainer; Stringhini, Silvia; Blane, David; van der Linden, Bernadette W A; Kliegel, Matthias; Burton-Jeangros, Claudine; Courvoisier, Delphine S; Cullati, Stéphane

2018-05-01

socioeconomic circumstances (SEC) during a person's lifespan influence a wide range of health outcomes. However, solid evidence of the association of early- and adult-life SEC with health trajectories in ageing is still lacking. This study assessed whether early-life SEC are associated with muscle strength in later life-a biomarker of health-and whether this relationship is caused by adult-life SEC and health behaviours. we used data from the Survey of Health Ageing and Retirement in Europe, a 12-year population-based cohort study with repeated measurement in six waves (2004-15) and retrospective collection of life-course data. Participants' grip strength was assessed by using a handheld dynamometer. Confounder-adjusted logistic mixed-effect models were used to examine the associations of early- and adult-life SEC with the risk of low muscle strength (LMS) in older age. a total of 24,179 participants (96,375 observations) aged 50-96 living in 14 European countries were included in the analyses. Risk of LMS was increased with disadvantaged relative to advantaged early-life SEC. The association between risk of LMS and disadvantaged early-life SEC gradually decreased when adjusting for adult-life SEC for both sexes and with unhealthy behaviours for women. After adjusting for these factors, all associations between risk of LMS and early-life SEC remained significant for women. early-life SEC are associated with muscle strength after adjusting for adult-life SEC and behavioural lifestyle factors, especially in women, which suggests that early life may represent a sensitive period for future health.

Early Changes in Clinical, Functional, and Laboratory Biomarkers in Workers at Risk of Indium Lung Disease

PubMed Central

Virji, M. Abbas; Trapnell, Bruce C.; Carey, Brenna; Healey, Terrance; Kreiss, Kathleen

2014-01-01

Rationale: Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods: Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results: Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions: In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum

The early Earth atmosphere and early life catalysts.

PubMed

Ramírez Jiménez, Sandra Ignacia

2014-01-01

Homochirality is a property of living systems on Earth. The time, the place, and the way in which it appeared are uncertain. In a prebiotic scenario two situations are of interest: either an initial small bias for handedness of some biomolecules arouse and progressed with life, or an initial slight excess led to the actual complete dominance of the known chiral molecules. A definitive answer can probably never be given, neither from the fields of physics and chemistry nor biology. Some arguments can be advanced to understand if homochirality is necessary for the initiation of a prebiotic homochiral polymer chemistry, if this homochirality is suggesting a unique origin of life, or if a chiral template such as a mineral surface is always required to result in an enantiomeric excess. A general description of the early Earth scenario will be presented in this chapter, followed by a general description of some clays, and their role as substrates to allow the concentration and amplification of some of the building blocks of life.

Early-Life Effects on Adult Physical Activity: Concepts, Relevance, and Experimental Approaches.

PubMed

Garland, Theodore; Cadney, Marcell D; Waterland, Robert A

Locomotion is a defining characteristic of animal life and plays a crucial role in most behaviors. Locomotion involves physical activity, which can have far-reaching effects on physiology and neurobiology, both acutely and chronically. In human populations and in laboratory rodents, higher levels of physical activity are generally associated with positive health outcomes, although excessive exercise can have adverse consequences. Whether and how such relationships occur in wild animals is unknown. Behavioral variation among individuals arises from genetic and environmental factors and their interactions as well as from developmental programming (persistent effects of early-life environment). Although tremendous progress has been made in identifying genetic and environmental influences on individual differences in behavior, early-life effects are not well understood. Early-life effects can in some cases persist across multiple generations following a single exposure and, in principle, may constrain or facilitate the rate of evolution at multiple levels of biological organization. Understanding the mechanisms of such transgenerational effects (e.g., exposure to stress hormones in utero, inherited epigenetic alterations) may prove crucial to explaining unexpected and/or sex-specific responses to selection as well as limits to adaptation. One area receiving increased attention is early-life effects on adult physical activity. Correlational data from epidemiological studies suggest that early-life nutritional stress can (adversely) affect adult human activity levels and associated physiological traits (e.g., body composition, metabolic health). The few existing studies of laboratory rodents demonstrate that both maternal and early-life exercise can affect adult levels of physical activity and related phenotypes. Going forward, rodents offer many opportunities for experimental studies of (multigenerational) early-life effects, including studies that use maternal

Rural versus urban differences in end-of-life care for lung cancer patients in Germany.

PubMed

Walter, Julia; Tufman, Amanda; Leidl, Reiner; Holle, Rolf; Schwarzkopf, Larissa

2018-07-01

To assess rural-urban differences in healthcare utilization and supportive care at the end-of-life in German lung cancer patients. We identified 12,929 patients with incident lung cancer in 2009 from claims data and categorized them to four district types (major city, urban, rural, remote rural). We compared site of death, unplanned hospitalizations, hospital days, outpatient doctor, general practitioner (GP) and home visits, structured palliative care, therapy with antidepressants, pain relief medication and chemotherapy, and therapeutic puncturing in the last 30 and 14 days of life using mixed models with logistic link function for binary outcomes and log link function for count data. We adjusted all models by age, sex, comorbidities, metastases location and presence of multiple tumors at diagnosis, survival in months, and type of tumor-directed treatment. We found significant differences in two of the outcomes measured. The likelihood of > 14 hospital days in the last 30 days was significantly higher in rural districts than in remote rural districts (1.27 [1.05, 1.52], p = 0.0003). The number of visits to the GP in the last 30 days of life was significantly lower in urban districts than in remote rural districts (β = - 0.19 [- 0.32, - 0.06], p = <0.0001). No other endpoints were associated with regional differences. Triggering factors for high and low utilization of healthcare were mostly age, comorbidities, and prior anticancer treatment. Healthcare utilization and supportive care did not differ significantly between different district types. Results reject the hypothesis of regional inequity in end-of-life care of lung cancer patients in Germany.

Sleep disorders and health-related quality of life in patients with interstitial lung disease.

PubMed

Mavroudi, Maria; Papakosta, Despoina; Kontakiotis, Theodore; Domvri, Kaliopi; Kalamaras, George; Zarogoulidou, Vasiliki; Zarogoulidis, Paul; Latka, Paschalina; Huang, Haidong; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Konstantinos

2018-05-01

Interstitial lung diseases (ILD) are chronic and restrictive lung diseases with poor survival and quality of life. The aim of this study was to investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis (IPF) and sarcoidosis and to assess patients' quality of life in relation to these disorders. Forty patients, 19 with IPF, and 21 with sarcoidosis stage II/III were included. They were compared with 15 healthy subjects. All patients performed all-night polysomnography (PSG) and completed the Epworth, Berlin, and Stop-Bang questionnaires. In order to evaluate the quality of life, all patients completed the Short-Form 36 (SF-36) questionnaire. Of the IPF patients, 68% were diagnosed with mild obstructive sleep apnea (OSA), 5.2% with moderate to severe, 5.2% with severe OSA, and 21% with no OSA. Of patients with sarcoidosis, 52.4% were diagnosed with mild OSA and 4.8% with moderate severity OSA. The remaining 42.8% did not have OSA. The health-related quality of life in both patients with IPF and patients with sarcoidosis was impaired especially in the domains concerning physical health and the level of independence, compared to the control group. In this sample of patients with IPF and sarcoidosis, obstructive sleep apnea is common at least in a mild degree of severity. The SF-36 questionnaire may be a useful tool for the evaluation of the quality of life in these patients.

Reduced survival in patients with early-stage non-small-cell lung cancer is associated with high pleural endothelial progenitor cell levels.

PubMed

Pirro, Matteo; Cagini, Lucio; Mannarino, Massimo R; Andolfi, Marco; Potenza, Rossella; Paciullo, Francesco; Bianconi, Vanessa; Frangione, Maria Rosaria; Bagaglia, Francesco; Puma, Francesco; Mannarino, Elmo

2016-12-01

Endothelial progenitor cells are capable of contributing to neovascularization in tumours. In patients with either malignant or transudative pleural effusion, we tested the presence of pleural endothelial progenitor cells. We also measured the number of endothelial progenitor cells in post-surgery pleural drainage of either patients with early non-small-cell lung cancer or control patients with benign lung disease undergoing pulmonary resection. The prospective influence of post-surgery pleural-drainage endothelial progenitor cells on cancer recurrence/survival was investigated. Pleural endothelial progenitor cell levels were quantified by fluorescence-activated cell sorting analysis in pleural effusion of 15 patients with late-stage non-small-cell lung cancer with pleural involvement and in 15 control patients with congestive heart failure. Also, pleural-drainage endothelial progenitor cells were measured in pleural-drainage fluid 48 h after surgery in 64 patients with early-stage non-small-cell lung cancer and 20 benign lung disease patients undergoing pulmonary resection. Cancer recurrence and survival was evaluated in patients with high pleural-drainage endothelial progenitor cell levels. The number of pleural endothelial progenitor cells was higher in non-small-cell lung cancer pleural effusion than in transudative pleural effusion. Also, pleural-drainage endothelial progenitor cell levels were higher in patients with non-small-cell lung cancer than in patients with benign lung disease undergoing pulmonary resection (P < 0.05). Non-small-cell lung cancer patients with high pleural-drainage endothelial progenitor cell levels had a significantly 4.9 higher rate of cancer recurrence/death than patients with lower pleural-drainage endothelial progenitor cell levels, irrespective of confounders. Endothelial progenitor cells are present in the pleural effusion and are higher in patients with late-stage non-small-cell lung cancer with pleural involvement than in

The human early-life exposome (HELIX): project rationale and design.

PubMed

Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

2014-06-01

Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

Early-life income inequality and adolescent health and well-being.

PubMed

Elgar, Frank J; Gariépy, Geneviève; Torsheim, Torbjørn; Currie, Candace

2017-02-01

A prevailing hypothesis about the association between income inequality and poor health is that inequality intensifies social hierarchies, increases stress, erodes social and material resources that support health, and subsequently harms health. However, the evidence in support of this hypothesis is limited by cross-sectional, ecological studies and a scarcity of developmental studies. To address this limitation, we used pooled, multilevel data from the Health Behaviour in School-aged Children study to examine lagged, cumulative, and trajectory associations between early-life income inequality and adolescent health and well-being. Psychosomatic symptoms and life satisfaction were assessed in surveys of 11- to 15-year-olds in 40 countries between 1994 and 2014. We linked these data to national Gini indices of income inequality for every life year from 1979 to 2014. The results showed that exposure to income inequality from 0 to 4 years predicted psychosomatic symptoms and lower life satisfaction in females after controlling lifetime mean income inequality, national per capita income, family affluence, age, and cohort and period effects. The cumulative income inequality exposure in infancy and childhood (i.e., average Gini index from birth to age 10) related to lower life satisfaction in female adolescents but not to symptoms. Finally, individual trajectories in early-life inequality (i.e., linear slopes in Gini indices from birth to 10 years) related to fewer symptoms and higher life satisfaction in females, indicating that earlier exposures mattered more to predicting health and wellbeing. No such associations with early-life income inequality were found in males. These results help to establish the antecedent-consequence conditions in the association between income inequality and health and suggest that both the magnitude and timing of income inequality in early life have developmental consequences that manifest in reduced health and well-being in adolescent girls

Serum pleiotrophin could be an early indicator for diagnosis and prognosis of non-small cell lung cancer.

PubMed

Du, Zi-Yan; Shi, Min-Hua; Ji, Cheng-Hong; Yu, Yong

2015-01-01

Pleiotrophin (PTN), an angiogenic factor, is associated with various types of cancer, including lung cancer. Our aim was to investigate the possibility of using serum PTN as an early indicator regarding disease diagnosis, classification and prognosis, for patients with non-small cell lung cancer (NSCLC). Significant differences among PTN levels in patients with small cell lung cancer (SCLC, n=40), NSCLC (n=136), and control subjects with benign pulmonary lesions (n=21), as well as patients with different pathological subtypes of NSCLC were observed. A serum level of PTN of 300.1 ng/ml, was determined as the cutoff value differentiating lung cancer patients and controls, with a sensitivity and specificity of 78.4% and 66.7%, respectively. Negative correlations between serum PTN level and pathological differentiation level, stage, and survival time were observed in our cohort of patients with NSCLC. In addition, specific elevation of PTN levels in pulmonary tissue in and around NSCLC lesions in comparison to normal pulmonary tissue obtained from the same subjects was also observed (n=2). This study suggests that the serum PTN level of patients with NSCLC could be an early indicator for diagnosis and prognosis. This conclusion should be further assessed in randomized clinical trials.

Children of Misfortune: Early Adversity and Cumulative Inequality in Perceived Life Trajectories1

PubMed Central

Schafer, Markus H.; Ferraro, Kenneth F.; Mustillo, Sarah A.

2011-01-01

Adversity early in life may alter pathways of aging, but what interpretive processes can soften the blow of early insults? Drawing from cumulative inequality theory, the authors analyze trajectories of life evaluations and then consider whether early adversity offsets favorable expectations for the future. Results reveal that early adversity contributes to more negative views of the past but rising expectations for the future. Early adversity also has enduring effects on life evaluations, offsetting the influence of buoyant expectations. The findings draw attention to the limits of human agency under the constraints of early adversity—a process described as biographical structuration. PMID:21648247

Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

PubMed Central

Tain, You-Lin; Hsu, Chien-Ning

2017-01-01

Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK.

PubMed

Fisher, Andrew; Andreasson, Anders; Chrysos, Alexandros; Lally, Joanne; Mamasoula, Chrysovalanto; Exley, Catherine; Wilkinson, Jennifer; Qian, Jessica; Watson, Gillian; Lewington, Oli; Chadwick, Thomas; McColl, Elaine; Pearce, Mark; Mann, Kay; McMeekin, Nicola; Vale, Luke; Tsui, Steven; Yonan, Nizar; Simon, Andre; Marczin, Nandor; Mascaro, Jorge; Dark, John

2016-11-01

dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study. Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation. Current Controlled Trials ISRCTN

Pulmonary rehabilitation in lung transplant candidates.

PubMed

Li, Melinda; Mathur, Sunita; Chowdhury, Noori A; Helm, Denise; Singer, Lianne G

2013-06-01

While awaiting lung transplantation, candidates may participate in pulmonary rehabilitation to improve their fitness for surgery. However, pulmonary rehabilitation outcomes have not been systematically evaluated in lung transplant candidates. This investigation was a retrospective cohort study of 345 pre-transplant pulmonary rehabilitation participants who received a lung transplant between January 2004 and June 2009 and had available pre-transplant exercise data. Data extracted included: 6-minute walk tests at standard intervals; exercise training details; health-related quality-of-life (HRQL) measures; and early post-transplant outcomes. Paired t-tests were used to examine changes in the 6MW distance (6MWD), exercise training volume and HRQL during the pre-transplant period. We evaluated the association between pre-transplant 6MWD and transplant hospitalization outcomes. The final 6MWD prior to transplantation was only 15 m less than the listing 6MWD (n = 200; p = 0.002). Exercise training volumes increased slightly from the start of the pulmonary rehabilitation program until transplant: treadmill, increase 0.69 ml/kg/min (n = 238; p < 0.0001); biceps resistance training, 18 lbs. × reps (n = 286; p < 0.0001); and quadriceps resistance training, 15 lbs. × reps (n = 278; p < 0.0001). HRQL measures declined. A greater final 6MWD prior to transplant correlated with a shorter length of stay in the hospital (n = 207; p = 0.003). Exercise capacity and training volumes are well preserved among lung transplant candidates participating in pulmonary rehabilitation, even in the setting of severe, progressive lung disease. Participants with greater exercise capacity prior to transplantation have more favorable early post-transplant outcomes. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico

PubMed Central

DeGraff, Deborah S.; Wong, Rebeca

2014-01-01

This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth. PMID:25170434

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

PubMed Central

Pohl, Calvin S.; Medland, Julia E.

2015-01-01

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

A prospective cohort study among new Chinese coal miners: the early pattern of lung function change.

PubMed

Wang, M-L; Wu, Z-E; Du, Q-G; Petsonk, E L; Peng, K-L; Li, Y-D; Li, S-K; Han, G-H; Atffield, M D

2005-11-01

To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

Dietary factors during early life program bone formation in female rats

USDA-ARS?s Scientific Manuscript database

Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases; however, evidence for an association between early life dietary factors and bone health in adults is limited. Soy protein isolate (SPI) may be one such dietary factor that promotes bone accretion du...

Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma

PubMed Central

Bueno, Raphael; Hughes, Elisha; Wagner, Susanne; Gutin, Alexander S.; Lanchbury, Jerry S.; Zheng, Yifan; Archer, Michael A.; Gustafson, Corinne; Jones, Joshua T.; Rushton, Kristen; Saam, Jennifer; Kim, Edward; Barberis, Massimo; Wistuba, Ignacio; Wenstrup, Richard J.; Wallace, William A.; Harrison, David J.

2015-01-01

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality. PMID:25396679

The Relationship Between Early Life Events, Parental Attachment, and Psychopathic Tendencies in Adolescent Detainees.

PubMed

Christian, Erica J; Meltzer, Christine L; Thede, Linda L; Kosson, David S

2017-04-01

Despite increasing interest in understanding psychopathic traits in youth, the role of early environmental factors in the development of psychopathic traits is not well understood. No prior studies have directly examined the relationship between early life events and psychopathic traits. We examined links between life events in the first 4 years of life and indices of the core affective and interpersonal components of psychopathy. Additionally, we examined relationships between early life events, psychopathic traits, and attachment to parents among 206 adjudicated adolescents. Results indicated that the total number of early life events was positively correlated with indices of the affective component of psychopathy. Moreover, psychopathic traits moderated the relationship between the number of early life events and later reports of attachment to parents. Findings suggest that early environmental factors could have important implications for the development of psychopathic traits and may impact attachment to parents for youth with psychopathic traits.

Early life nutrition, epigenetics and programming of later life disease.

PubMed

Vickers, Mark H

2014-06-02

The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be

Socioeconomic position and surgery for early-stage non-small-cell lung cancer: A population-based study in Denmark.

PubMed

Kærgaard Starr, Laila; Osler, Merete; Steding-Jessen, Marianne; Lidegaard Frederiksen, Birgitte; Jakobsen, Erik; Østerlind, Kell; Schüz, Joachim; Johansen, Christoffer; Oksbjerg Dalton, Susanne

2013-03-01

To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall and separately for stages I, II and IIIa. Of the 5538 eligible patients with stages I-IIIa NSCLC diagnosed 2001-2008, 53% underwent surgery. Higher stage, older age, being female and diagnosis early in the study period were associated with higher odds for not receiving surgery. Low disposable income was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain the association with income or living alone for early-stage NSCLC patients. Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors. Thus, even in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

PubMed

Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

2015-12-15

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

Impact of capsaicin, an active component of chili pepper, on pathogenic chlamydial growth (Chlamydia trachomatis and Chlamydia pneumoniae) in immortal human epithelial HeLa cells.

PubMed

Yamakawa, Kazuya; Matsuo, Junji; Okubo, Torahiko; Nakamura, Shinji; Yamaguchi, Hiroyuki

2018-02-01

Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide. Capsaicin, a component of chili pepper, which can stimulate actin remodeling via capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) and anti-inflammatory effects via PPARγ (peroxisome proliferator-activated receptor-γ) and LXRα (liver X receptor α), is a potential candidate to control chlamydial growth in host cells. We examined whether capsaicin could inhibit C. trachomatis growth in immortal human epithelial HeLa cells. Inclusion forming unit and quantitative PCR assays showed that capsaicin significantly inhibited bacterial growth in cells in a dose-dependent manner, even in the presence of cycloheximide, a eukaryotic protein synthesis inhibitor. Confocal microscopic and transmission electron microscopic observations revealed an obvious decrease in bacterial numbers to inclusions bodies formed in the cells. Although capsaicin can stimulate the apoptosis of cells, no increase in cleaved PARP (poly (ADP-ribose) polymerase), an apoptotic indicator, was observed at a working concentration. All of the drugs tested (capsazepine, a TRPV1 antagonist; 5CPPSS-50, an LXRα inhibitor; and T0070907, a PPARγ inhibitor) had no effect on chlamydial inhibition in the presence of capsaicin. In addition, we also confirmed that capsaicin inhibited Chlamydia pneumoniae growth, indicating a phenomena not specific to C. trachomatis. Thus, we conclude that capsaicin can block chlamydial growth without the requirement of host cell protein synthesis, but by another, yet to be defined, mechanism. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Racial-Ethnic Disparities in End-of-Life Care Quality among Lung Cancer Patients: A SEER-Medicare-Based Study.

PubMed

Karanth, Siddharth; Rajan, Suja S; Sharma, Gulshan; Yamal, Jose-Miguel; Morgan, Robert O

2018-05-10

Cancer end-of-life care and associated racial-ethnic disparities have been in focus during the last few years due to concerns regarding subjective care variations and poor quality of care. Given the high mortality rate and disease burden of lung cancer, end-of-life care quality is particularly crucial for this disease. This study uses previously validated measures and examines racial-ethnic disparities in lung cancer end-of-life care quality. This study involves retrospective analysis of patients ≥66 years, who were diagnosed with stage I-IV lung cancer, and who died on or before December 31, 2013, using the Surveillance Epidemiology and End Result-Medicare data from 1991-2013. Poor quality of care was measured using three themes: (1) potentially preventable medical encounters, (2) delayed hospice referral, and (3) aggressive chemotherapy provision during end-of-life. The patients were analyzed as two separate cohorts of NSCLC and SCLC patients. Logistic regression analyses were performed to estimate racial-ethnic disparities in the adjusted odds of receiving poor quality end-of-life care. The study found considerable racial-ethnic disparities in end-of-life care quality. The racial-ethnic minorities had higher odds of experiencing potentially preventable medical encounters in the last month of life as compared with non-Hispanic whites. Odds of delayed hospice referral and aggressive chemotherapy provision during end-of-life were lower in non-Hispanic blacks as compared with non-Hispanic whites. The study findings highlight the continued lack of access and care disparity among the minorities, which could precipitate potentially preventable utilizations, and limit access to hospice care during end-of-life. The study suggests the need to develop educational, patient navigational and other interventions that could potentially reduce aggressive utilizations and improve appropriate hospice care provision during end-of-life. Copyright © 2018. Published by Elsevier Inc.

The Lung Microbiome After Lung Transplantation

PubMed Central

Becker, Julia B.; Poroyko, Valeriy

2014-01-01

Summary Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome’s role in the failing lung allograft. PMID:24601662

Breath analysis system for early detection of lung diseases based on multi-sensor array

NASA Astrophysics Data System (ADS)

Jeon, Jin-Young; Yu, Joon-Boo; Shin, Jeong-Suk; Byun, Hyung-Gi; Lim, Jeong-Ok

2013-05-01

Expiratory breath contains various VOCs(Volatile Organic Compounds) produced from the human. When a certain disease exists, the exhalation has specific VOCs which may be generated from diseases. Many researchers have been actively working to find different types of biomarkers which are characteristic for particular diseases. Research regarding the identification of specific diseases from exhalation is still in progress. The aim of this research is to implement early detection of lung disease such as lung cancer and COPD(Chronic Obstructive Pulmonary Disease), which was nominated on the 6th of domestic death rate in 2010, based on multi-sensor array system. The system has been used to acquire sampled expiratory gases data and PCA(Principle Component Analysis) technique was applied to analyze signals from multi-sensor array. Throughout the experimental trials, a clearly distinguishable difference between lung disease patients and healthy controls was found from the measurement and analysis of their respective expiratory gases.

Identifying community perspectives for a lung cancer screening awareness campaign in Appalachia Kentucky: The Terminate Lung Cancer (TLC) Study

PubMed Central

Cardarelli, Roberto; Roper, Karen L.; Cardarelli, Kathryn; Feltner, Frances J.; Prater, Shirley; Ledford, Karen Michelle; Justice, Barbara; Reese, David R.; Wagner, Patsy; Cantrell, Christine

2017-01-01

Introduction Lung cancer screening with low-dose computed tomography (LDCT) scan is now covered by Centers for Medicare & Medicaid Services following an evidence-based recommendation, but a shared decision making process should inform patients of risks and limitations. An awareness campaign promoting LDCT screenings is an opportunity to elicit patient engagement with health providers about the risks and benefits. Focus groups representing three regions of Appalachian Kentucky known for high lung cancer rates discussed development of a lung cancer screening campaign. Recommendations included messaging content, appeals or design, campaign implementation, and trusted information or communication sources. Methods Community health workers (CHWs) from three Eastern Kentucky regions recruited individuals from their local communities using established client files. CHWs hosted six total focus groups (7–11 participants each) using questions guided by the Communication-Persuasion Matrix framework. All sessions were recorded and transcribed for independent content analysis. Results A total of fifty-four individuals (61.1% female; >55 pack year history) participated. Prior to discussion, most participants had not heard of lung cancer screening. Cited needs for content of a campaign included benefits of early detection and payment information. Messages considered most persuasive were those that include: personal testimony, messages of hope, prolonged life, and an emphasis on family and the ambition to survive. Having information come from one’s family doctor or specialty provider was considered important to message communication. Conclusions Messages about survivorship, family, and prolonged life should be considered in lung cancer screening awareness campaigns. Our results provide community input about messages regarding screening options. PMID:26411308

Early evolution without a tree of life.

PubMed

Martin, William F

2011-06-30

Life is a chemical reaction. Three major transitions in early evolution are considered without recourse to a tree of life. The origin of prokaryotes required a steady supply of energy and electrons, probably in the form of molecular hydrogen stemming from serpentinization. Microbial genome evolution is not a treelike process because of lateral gene transfer and the endosymbiotic origins of organelles. The lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause.

The origin and early evolution of life on earth

NASA Technical Reports Server (NTRS)

Oro, J.; Miller, Stanley L.; Lazcano, Antonio

1990-01-01

Results of the studies that have provided insights into the cosmic and primitive earth environments are reviewed with emphasis on those environments in which life is thought to have originated. The evidence bearing on the antiquity of life on the earth and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar-system bodies such as comets, dark asteroids, and carbonaceous chondrites are assessed. The environmental models of the Hadean and early Archean earth are discussed, as well as the prebiotic formation of organic monomers and polymers essential to life. The processes that may have led to the appearance in the Archean of the first cells are considered, and possible effects of these processes on the early steps of biological evolution are analyzed. The significance of these results to the study of the distribution of life in the universe is evaluated.

The status of live viral vaccination in early life.

PubMed

Gans, Hayley A

2013-05-17

The need for neonatal vaccines is supported by the high disease burden during the first year of life particularly in the first month. Two-thirds of childhood deaths are attributable to infectious diseases of which viruses represent key pathogens. Many infectious diseases have the highest incidence, severity and mortality in the first months of life, and therefore early life vaccination would provide significant protection and life savings. For some childhood viral diseases successful vaccines exist, such as against measles, mumps, rubella, varicella, influenza poliovirus, and rotavirus, but their use in the first year particularly at birth is not yet practiced. Vaccines against other key pathogens continue to elude scientists such as against respiratory syncytial virus. The obstacles for early and neonatal vaccination are complex and include host factors, such as a developing immune system and the interference of passively acquired antibodies, as well vaccine-specific issues, such as optimal route of administration, titer and dosing requirements. Importantly, additional host and infrastructure barriers also present obstacles to neonatal vaccination in the developing world where morbidity and mortality rates are highest. This review will highlight the current live viral vaccines and their use in the first year of life, focusing on efficacy and entertaining the barriers that exist. It is important to understand the successes of current vaccines and use this knowledge to determine strategies that are successful in young infants and for the development of new vaccines for use in early life. Copyright © 2012 Elsevier Ltd. All rights reserved.

EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

EPA Science Inventory

Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

Early-Life Social Origins of Later-Life Body Weight: The Role of Socioeconomic Status and Health Behaviors over the Life Course

PubMed Central

Logan, Ellis Scott; Richman, Aliza

2014-01-01

Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage. PMID:24767590

Early-Life Food Nutrition, Microbiota Maturation and Immune Development Shape Life-Long Health.

PubMed

Zhou, Xiaoli; Du, Lina; Shi, Ronghua; Chen, Zhidong; Zhou, Yiming; Li, Zongjie

2018-06-06

The current knowledge about early-life nutrition and environmental factors that affect the interaction between the symbiotic microbiota and the host immune system has demonstrated novel regulatory target for treating allergic diseases, autoimmune disorders and metabolic syndrome. Various kinds of food nutrients (such as dietary fiber, starch, polyphenols and proteins) can provide energy resources for both intestinal microbiota and the host. The indigestible food components are fermented by the indigenous gut microbiota to produce diverse metabolites, including short-chain fatty acids, bile acids and trimethylamine-N-oxide, which can regulate the host metabolized physiology, immunity homeostasis and health state. Therefore it is commonly believed early-life perturbation of the microbial community structure and the dietary nutrition interference on the child mucosal immunity contribute to the whole life susceptibility to chronic diseases. In all, the combined interrelationship between food ingredients nutrition, intestinal microbiota configurations and host system immunity provides new therapeutic targets to treat various kinds of pathogenic inflammations and chronic diseases.

An experimental demonstration that early-life competitive disadvantage accelerates telomere loss.

PubMed

Nettle, Daniel; Monaghan, Pat; Gillespie, Robert; Brilot, Ben; Bedford, Thomas; Bateson, Melissa

2015-01-07

Adverse experiences in early life can exert powerful delayed effects on adult survival and health. Telomere attrition is a potentially important mechanism in such effects. One source of early-life adversity is the stress caused by competitive disadvantage. Although previous avian experiments suggest that competitive disadvantage may accelerate telomere attrition, they do not clearly isolate the effects of competitive disadvantage from other sources of variation. Here, we present data from an experiment in European starlings (Sturnus vulgaris) that used cross-fostering to expose siblings to divergent early experience. Birds were assigned either to competitive advantage (being larger than their brood competitors) or competitive disadvantage (being smaller than their brood competitors) between days 3 and 12 post-hatching. Disadvantage did not affect weight gain, but it increased telomere attrition, leading to shorter telomere length in disadvantaged birds by day 12. There were no effects of disadvantage on oxidative damage as measured by plasma lipid peroxidation. We thus found strong evidence that early-life competitive disadvantage can accelerate telomere loss. This could lead to faster age-related deterioration and poorer health in later life.

The origin and early evolution of life on Earth.

PubMed

Oró, J; Miller, S L; Lazcano, A

1990-01-01

We do not have a detailed knowledge of the processes that led to the appearance of life on Earth. In this review we bring together some of the most important results that have provided insights into the cosmic and primitive Earth environments, particularly those environments in which life is thought to have originated. To do so, we first discuss the evidence bearing on the antiquity of life on our planet and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar system bodies such as comets, dark asteroids, and carbonaceous chondrites. This is followed by a discussion on the environmental models of the Hadean and early Archean Earth, as well as on the prebiotic formation of organic monomers and polymers essential to life. We then consider the processes that may have led to the appearance in the Archean of the first cells, and how these processes may have affected the early steps of biological evolution. Finally, the significance of these results to the study of the distribution of life in the Universe is discussed.

Early-life chemical exposures and risk of metabolic syndrome.

PubMed

De Long, Nicole E; Holloway, Alison C

2017-01-01

The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate) and processing (acrylamide), in addition to chemicals ubiquitously found in our household goods (brominated flame retardants) and drinking water (heavy metals) and changes in key pathways important for the development of MetS and obesity.

Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life.

PubMed

Nakamoto, Tetsuo; Rawls, H Ralph

2018-05-15

Fluoride, one of the most celebrated ingredients for the prevention of dental caries in the 20th century, has also been controversial for its use in dentifrices and other applications. In the current review, we have concentrated primarily on early-life exposure to fluoride and how it may affect the various organs. The most recent controversial aspects of fluoride are related to toxicity of the developing brain and how it may possibly result in the decrease of intelligence quotient (IQ), autism, and calcification of the pineal gland. In addition, it has been reported to have possible effects on bone and thyroid glands. If nutritional stress is applied during a critical period of growth and development, the organ(s) and/or body will never recover once they pass through the critical period. For example, if animals are force-fed during experiments, they will simply get fat but never reach the normal size. Although early-life fluoride exposure causing fluorosis is well reported in the literature, the dental profession considers it primarily as an esthetic rather than a serious systemic problem. In the current review, we wanted to raise the possibility of future disease as a result of early-life exposure to fluoride. It is not currently known how fluoride will become a cause of future disease. Studies of other nutritional factors have shown that the effects of early nutritional stress are a cause of disease in later life.

Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals.

PubMed

Chistiakov, Dimitry A; Chekhonin, Vladimir P

2017-06-05

To examine whether chronic physical aggression (CPA) in adulthood can be epigenetically programmed early in life due to exposure to early-life adversity. Literature search of public databases such as PubMed/MEDLINE and Scopus. Children/adolescents susceptible for CPA and exposed to early-life abuse fail to efficiently cope with stress that in turn results in the development of CPA later in life. This phenomenon was observed in humans and animal models of aggression. The susceptibility to aggression is a complex trait that is regulated by the interaction between environmental and genetic factors. Epigenetic mechanisms mediate this interaction. Subjects exposed to stress early in life exhibited long-term epigenetic programming that can influence their behaviour in adulthood. This programming affects expression of many genes not only in the brain but also in other systems such as neuroendocrine and immune. The propensity to adult CPA behaviour in subjects experienced to early-life adversity is mediated by epigenetic programming that involves long-term systemic epigenetic alterations in a whole genome.

Early life family conflict, Social interactions and Carotid Artery Intima-Media Thickness in Adulthood

PubMed Central

John-Henderson, Neha A.; Kamarck, Thomas W.; Muldoon, Matthew F.; Manuck, Stephen B.

2015-01-01

Objective Conflict in early life family environments is known to affect psychosocial functioning and coping styles into adulthood and is reported to negatively affect access to psychosocial resources that are critical to the management of stress. However, it remains unknown whether early life family conflict similarly affects subclinical cardiovascular disease (CVD) in adulthood. We predicted that family conflict in early life would be associated with greater mean Intima-Media thickness (IMT), a subclinical marker of CVD risk, in adulthood. Methods Data were collected in a community sample of 503 adults (47.4 % male, mean age: 42.8 years [SD=7.3]). Associations between family conflict in early life with IMT (assessed using B-mode ultrasound) in adulthood were examined using regression analysis. We also tested for indirect effects of early life family conflict on mean IMT through ecological momentary assessment (EMA) reports of social interactions, diversity of social roles, and perceived social support. Results Linear regression analyses adjusted for demographics and physiological risk factors showed conflict in early life associated with greater mean IMT (β=0.08, t(447)=2.13, p=0.034, R2=0.46). Early life conflict was significantly related to diversity of social roles, perceived social support, and EMA reports of pleasant and social conflict interactions. Significant indirect effects of early life conflict on mean IMT were observed through fewer pleasant social interactions and more frequent social conflict interactions in adulthood (β = 0.001, 95% CI, 0.0001–0.0014 and β=0.001, 95% CI, 0.0002–0.0015, respectively). Conclusions These findings provide initial evidence that family conflict in early life heightens CVD risk in adulthood, in part by shaping the quality of adulthood social interactions. PMID:26809109

Early Life Family Conflict, Social Interactions, and Carotid Artery Intima-Media Thickness in Adulthood.

PubMed

John-Henderson, Neha A; Kamarck, Thomas W; Muldoon, Matthew F; Manuck, Stephen B

2016-04-01

Conflict in early life family environments is known to affect psychosocial functioning and coping styles into adulthood and is reported to negatively affect access to psychosocial resources that are critical to the management of stress. However, it remains unknown whether early life family conflict similarly affects subclinical cardiovascular disease (CVD) in adulthood. We predicted that family conflict in early life would be associated with greater mean intima-media thickness (IMT), a subclinical marker of CVD risk, in adulthood. Data were collected in a community sample of 503 adults (47.4 % male, mean [standard deviation] age = 42.8 [7.3] years). Associations between family conflict in early life with IMT (assessed using B-mode ultrasound) in adulthood were examined using regression analysis. We also tested for indirect effects of early life family conflict on mean IMT through ecological momentary assessment reports of social interactions, diversity of social roles, and perceived social support. Linear regression analyses adjusted for demographics and physiological risk factors showed conflict in early life associated with greater mean IMT (β = 0.08, t(447) = 2.13, p = .034, R = 0.46). Early life conflict was significantly related to diversity of social roles, perceived social support, and ecological momentary assessment reports of pleasant and social conflict interactions. Significant indirect effects of early life conflict on mean IMT were observed through fewer pleasant social interactions and more frequent social conflict interactions in adulthood (β = 0.001 [95% confidence interval = 0.0001-0.0014] and β = 0.001 [95% confidence interval = 0.0002-0.0015], respectively). These findings provide initial evidence that family conflict in early life heightens CVD risk in adulthood, in part by shaping the quality of adulthood social interactions.

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leeman, Jonathan E.; Rimner, Andreas; Montecalvo, Joseph

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. Methods and Materials: We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 Worldmore » Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non–high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score–weighted Cox regression models. Results: The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non–high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. Conclusions: The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype

Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy.

PubMed

Leeman, Jonathan E; Rimner, Andreas; Montecalvo, Joseph; Hsu, Meier; Zhang, Zhigang; von Reibnitz, Donata; Panchoo, Kelly; Yorke, Ellen; Adusumilli, Prasad S; Travis, William; Wu, Abraham J

2017-01-01

Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 World Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non-high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score-weighted Cox regression models. The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non-high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype determined from core biopsies is a prognostic factor and could have

Improving the Diagnostic Specificity of CT for Early Detection of Lung Cancer: 4D CT-Based Pulmonary Nodule Elastometry

DTIC Science & Technology

2015-10-01

2012, patients who received stereotactic ablative radiotherapy ( SABR ) for early stage non-small cell lung cancer were included in this study. All...comparing the elasticities of malignant PNs treated with stereotactic ablative radiotherapy ( SABR ) with those of the lung. Methods: We analyzed...breath-hold images of 30 patients with malignant PNs who underwent SABR in our department. A parametric nonrigid transformation model based on multi

Prevention of overweight and obesity in early life.

PubMed

Lanigan, Julie

2018-05-29

Childhood obesity is a serious challenge for public health. The problem begins early with most excess childhood weight gained before starting school. In 2016, the WHO estimated that 41 million children under 5 were overweight or obese. Once established, obesity is difficult to reverse, likely to persist into adult life and is associated with increased risk of CVD, type 2 diabetes and certain cancers. Preventing obesity is therefore of high importance. However, its development is multi-factorial and prevention is a complex challenge. Modifiable lifestyle behaviours such as diet and physical activity are the most well-known determinants of obesity. More recently, early-life factors have emerged as key influencers of obesity in childhood. Understanding risk factors and how they interact is important to inform interventions that aim to prevent obesity in early childhood. Available evidence supports multi-component interventions as effective in obesity prevention. However, relatively few interventions are available in the UK and only one, TrimTots, has been evaluated in randomised controlled trials and shown to be effective at reducing obesity risk in preschool children (age 1-5 years). BMI was lower in children immediately after completing TrimTots compared with waiting list controls and this effect was sustained at long-term follow-up, 2 years after completion. Developing and evaluating complex interventions for obesity prevention is a challenge for clinicians and researchers. In addition, parents encounter barriers engaging with interventions. This review considers early-life risk factors for obesity, highlights evidence for preventative interventions and discusses barriers and facilitators to their success.

Early respiratory acidosis is a new risk factor for pneumonia after lung resection.

PubMed

Planquette, Benjamin; Le Pimpec-Barthes, Françoise; Trinquart, Ludovic; Meyer, Guy; Riquet, Marc; Sanchez, Olivier

2012-03-01

Postoperative pneumonia (POP) is a life-threatening complication of lung resection (LR). Its risk factors, bacteriological profile and outcome are not well known. The aims of this study were to describe the outcome and causal bacteria and to identify risk factors for POP. We reviewed all cases admitted to intensive care after LR. Clinical parameters, operative and postoperative data were recorded. POP was suspected on the basis of fever, radiographic infiltrate, and either leucocytosis or purulent sputum. The diagnosis was confirmed by culture of a respiratory sample. Risk factors for POP were identified by univariate and multivariate analysis. We included 159 patients in this study. POP was diagnosed in 23 patients (14.4%) and was associated with a higher hospital mortality rate (30% versus 5%, P = 0.0007) and a longer hospital stay. Members of the Enterobacteriaceae and Pseudomonas species were the most frequently identified pathogens. Early respiratory acidosis (ERA; OR, 2.94; 95% CI, 1.1-8.1), blood transfusion (OR, 3.8; 95% CI, 1.1-13.1), bilobectomy (OR, 7.26; 95% CI, 1.2-43.1) and smoking history (OR, 1.84; 95% CI, 1.1-3) were identified as independent risk factors. ERA may be a risk factor for POP and could serve as a target for therapeutic interventions.

Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

PubMed

Shalev, Idan; Belsky, Jay

2016-05-01

Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of childhood anthropometry trends on adult lung function.

PubMed

Suresh, Sadasivam; O'Callaghan, Michael; Sly, Peter D; Mamun, Abdullah A

2015-04-01

Poor fetal growth rate is associated with lower respiratory function; however, there is limited understanding of the impact of growth trends and BMI during childhood on adult respiratory function. The current study data are from the Mater-University of Queensland Study of Pregnancy birth cohort. Prospective data were available from 1,740 young adults who performed standard spirometry at 21 years of age and whose birth weight and weight, height, and BMI at 5, 14, and 21 years of age were available. Catch-up growth was defined as an increase of 0.67 Z score in weight between measurements. The impact of catch-up growth on adult lung function and the relationship between childhood BMI trends and adult lung function were assessed using regression analyses. Lung function was higher at 21 years in those demonstrating catch-up growth from birth to 5 years (FVC, men: 5.33 L vs 5.54 L; women: 3.78 L vs 4.03 L; and FEV1, men: 4.52 L/s vs 4.64 L/s; women: 3.31 L/s vs 3.45 L/s). Subjects in the lowest quintile of birth (intrauterine growth retardation) also showed improved lung function if they had catch-up growth in the first 5 years of life. There was a positive correlation between increasing BMI and lung function at 5 years of age. However, in the later measurements when BMI increased into the obese category, a drop in lung function was observed. These data show evidence for a positive contribution of catch-up growth in early life to adult lung function. However, if weight gain or onset of obesity occurs after 5 years of age, an adverse impact on adult lung function is noted.

Social anxiety and negative early life events in university students.

PubMed

Binelli, Cynthia; Ortiz, Ana; Muñiz, Armando; Gelabert, Estel; Ferraz, Liliana; S Filho, Alaor; Crippa, José Alexandre S; Nardi, Antonio E; Subirà, Susana; Martín-Santos, Rocío

2012-06-01

There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

Early Life Nutrition and Energy Balance Disorders in Offspring in Later Life

PubMed Central

Reynolds, Clare M.; Gray, Clint; Li, Minglan; Segovia, Stephanie A.; Vickers, Mark H.

2015-01-01

The global pandemic of obesity and type 2 diabetes is often causally linked to changes in diet and lifestyle; namely increased intake of calorically dense foods and concomitant reductions in physical activity. Epidemiological studies in humans and controlled animal intervention studies have now shown that nutritional programming in early periods of life is a phenomenon that affects metabolic and physiological functions throughout life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. The mechanisms by which early environmental insults can have long-term effects on offspring remain poorly defined. However there is evidence from intervention studies which indicate altered wiring of the hypothalamic circuits that regulate energy balance and epigenetic effects including altered DNA methylation of key adipokines including leptin. Studies that elucidate the mechanisms behind these associations will have a positive impact on the health of future populations and adopting a life course perspective will allow identification of phenotype and markers of risk earlier, with the possibility of nutritional and other lifestyle interventions that have obvious implications for prevention of non-communicable diseases. PMID:26402696

Targeting of a chlamydial protease impedes intracellular bacterial growth.

PubMed

Christian, Jan G; Heymann, Julia; Paschen, Stefan A; Vier, Juliane; Schauenburg, Linda; Rupp, Jan; Meyer, Thomas F; Häcker, Georg; Heuer, Dagmar

2011-09-01

Chlamydiae are obligate intracellular bacteria that propagate in a cytosolic vacuole. Recent work has shown that growth of Chlamydia induces the fragmentation of the Golgi apparatus (GA) into ministacks, which facilitates the acquisition of host lipids into the growing inclusion. GA fragmentation results from infection-associated cleavage of the integral GA protein, golgin-84. Golgin-84-cleavage, GA fragmentation and growth of Chlamydia trachomatis can be blocked by the peptide inhibitor WEHD-fmk. Here we identify the bacterial protease chlamydial protease-like activity factor (CPAF) as the factor mediating cleavage of golgin-84 and as the target of WEHD-fmk-inhibition. WEHD-fmk blocked cleavage of golgin-84 as well as cleavage of known CPAF targets during infection with C. trachomatis and C. pneumoniae. The same effect was seen when active CPAF was expressed in non-infected cells and in a cell-free system. Ectopic expression of active CPAF in non-infected cells was sufficient for GA fragmentation. GA fragmentation required the small GTPases Rab6 and Rab11 downstream of CPAF-activity. These results define CPAF as the first protein that is essential for replication of Chlamydia. We suggest that this role makes CPAF a potential anti-infective therapeutic target.

Planetary Perspective on Life on Early Mars and the Early Earth

NASA Technical Reports Server (NTRS)

Sleep, Norman H.; Zahnle, Kevin

1996-01-01

Impacts of asteroids and comets posed a major hazard to the continuous existence of early life on Mars as on the Earth. The chief danger was presented by globally distributed ejecta, which for very large impacts takes the form of transient thick rock vapor atmospheres; both planets suffered such impacts repeatedly. The exposed surface on both planets was sterilized when it was quickly heated to the temperature of condensed rock vapor by radiation and rock rain. Shallow water bodies were quickly evaporated and sterilized. Any surviving life must have been either in deep water or well below the surface.

Proposals for the prevention of lung cancer in the health system of Mexico.

PubMed

Arrieta, Oscar; López-Mejía, Mariana; Macedo-Pérez, Eleazar Omar; Corona-Cruz, José Francisco

2016-04-01

The management of lung cancer is challenging. However, nowadays the main goal is to achieve a significant overall survival accompanied by a good quality of life. Because smoking is associated with up to 71% of cancer deaths, the first policy that should be established is one that promotes strategies for healthy lifestyles by providing information about lung cancer, risk factors, protection factors, and precautionary data. Furthermore, an effective screening method that would allow early diagnosis should be established. Following diagnosis, the patient should be genotyped to identify predisposing mutations to give personalized medicine to the patient. The health system policies should include information that affects the health of the population and simultaneously allows for early diagnoses, resulting in a higher survival rate.

Computed Tomography Assessment of Ablation Zone Enhancement in Patients With Early-Stage Lung Cancer After Stereotactic Ablative Radiotherapy.

PubMed

Moore, William; Chaya, Yair; Chaudhry, Ammar; Depasquale, Britney; Glass, Samantha; Lee, Susan; Shin, James; Mikhail, George; Bhattacharji, Priya; Kim, Bong; Bilfinger, Thomas

2015-01-01

Stereotactic ablative radiotherapy (SABR) offers a curative treatment for lung cancer in patients who are marginal surgical candidates. However, unlike traditional surgery the lung cancer remains in place after treatment. Thus, imaging follow-up for evaluation of recurrence is of paramount importance. In this retrospective designed Institutional Review Board-approved study, follow-up contrast-enhanced computed tomography (CT) exams were performed on sixty one patients to evaluate enhancement pattern in the ablation zone at 1, 3, 6, and 12 months after SABR. Eleven patients had recurrence within the ablation zone after SABR. The postcontrast enhancement in the recurrence group showed a washin and washout phenomenon, whereas the radiation-induced lung injury group showed continuous enhancement suggesting an inflammatory process. The textural feature of the ablation zone of enhancement and perfusion as demonstrated in computed tomography nodule enhancement may allow early differentiation of recurrence from radiation-induced lung injury in patients' status after SABR or primary lung cancer.

Promoting Career Development and Life Design in the Early Years of a Person's Life

ERIC Educational Resources Information Center

Maree, Jacobus G.

2018-01-01

The article discusses the changing world of work and the attendant uncertainty and loss of work-life identity. Little research has been done on career development and life design in the early years of a person's life, especially in developing countries characterized by disadvantage. The underlying theoretical models of career development are…

An experimental demonstration that early-life competitive disadvantage accelerates telomere loss

PubMed Central

Nettle, Daniel; Monaghan, Pat; Gillespie, Robert; Brilot, Ben; Bedford, Thomas; Bateson, Melissa

2015-01-01

Adverse experiences in early life can exert powerful delayed effects on adult survival and health. Telomere attrition is a potentially important mechanism in such effects. One source of early-life adversity is the stress caused by competitive disadvantage. Although previous avian experiments suggest that competitive disadvantage may accelerate telomere attrition, they do not clearly isolate the effects of competitive disadvantage from other sources of variation. Here, we present data from an experiment in European starlings (Sturnus vulgaris) that used cross-fostering to expose siblings to divergent early experience. Birds were assigned either to competitive advantage (being larger than their brood competitors) or competitive disadvantage (being smaller than their brood competitors) between days 3 and 12 post-hatching. Disadvantage did not affect weight gain, but it increased telomere attrition, leading to shorter telomere length in disadvantaged birds by day 12. There were no effects of disadvantage on oxidative damage as measured by plasma lipid peroxidation. We thus found strong evidence that early-life competitive disadvantage can accelerate telomere loss. This could lead to faster age-related deterioration and poorer health in later life. PMID:25411450

Early Identification of Patients at Risk of Acute Lung Injury

PubMed Central

Gajic, Ognjen; Dabbagh, Ousama; Park, Pauline K.; Adesanya, Adebola; Chang, Steven Y.; Hou, Peter; Anderson, Harry; Hoth, J. Jason; Mikkelsen, Mark E.; Gentile, Nina T.; Gong, Michelle N.; Talmor, Daniel; Bajwa, Ednan; Watkins, Timothy R.; Festic, Emir; Yilmaz, Murat; Iscimen, Remzi; Kaufman, David A.; Esper, Annette M.; Sadikot, Ruxana; Douglas, Ivor; Sevransky, Jonathan

2011-01-01

Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. Objectives: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). Methods: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Measurements and Main Results: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1–4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78–0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9–5.7). Conclusions: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772). PMID:20802164

A Psychometric Analysis of Quality of Life Tools in Lung Cancer Patients Who Smoke

PubMed Central

Browning, Kristine K.; Ferketich, Amy K.; Otterson, Gregory A.; Reynolds, Nancy R.; Wewers, Mary Ellen

2009-01-01

Lung cancer is the leading cause of cancer death for both men and women in the United States. Patient quality of life (QOL) prior to cancer treatment is known to be a strong predictor of survival and toleration of treatment toxicities. A lung cancer patient’s self-assessment of QOL is highly valued among clinicians as it guides treatment-related decisions and impacts clinical outcomes. Smokers are known to report a lower QOL. Limited research has been conducted on QOL outcomes in lung cancer patients who continue to smoke. To assess QOL, a reliable and valid QOL measure specific to lung cancer is required. The Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L) and Lung Cancer Symptom Scale (LCSS) are instruments that specifically examine QOL among lung cancer patients. The LCSS is a focused QOL instrument that includes physical and functional domains of QOL and disease symptomatology. The FACT-L is a broader QOL instrument that includes physical, functional, social and emotional domains and disease symptomatology. Both are psychometrically valid and are widely used in the literature, but have not been exclusively evaluated in smokers. Furthermore, there is no ‘gold standard’ instrument since there has never been a correlation study to compare estimates of reliability and validity between these instruments. The purpose of this study is to report the internal consistency and convergence validity of the FACT-L and the LCSS among newly diagnosed lung cancer patients who smoke. This data were collected and analyzed from a larger study examining smoking behavior among newly diagnosed lung cancer patients (n=51). Descriptive statistics were calculated on the FACT-L and LCSS scores, internal consistency was assessed by estimating Cronbach’s alpha coefficients, and Pearson correlation coefficients were estimated between the two scales. Internal consistency coefficients demonstrated good reliability for both scales, and the two instruments demonstrated a

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

PubMed

Hayden, Lystra P; Hardin, Megan E; Qiu, Weiliang; Lynch, David A; Strand, Matthew J; van Beek, Edwin J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

2018-02-01

Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression. Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. ClinicalTrials.gov; No. NCT00608764; https

Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer.

PubMed

Choi, S; Ryu, E

2018-01-01

People with advanced lung cancer experience later symptoms after treatment that is related to poorer psychosocial and quality of life (QOL) outcomes. The purpose of this study was to identify the effect of symptom clusters and depression on the QOL of patients with advanced lung cancer. A sample of 178 patients with advanced lung cancer at the National Cancer Center in Korea completed a demographic questionnaire, the M.D. Anderson Symptom Inventory-Lung Cancer, the Center for Epidemiological Studies Depression Scale, and the Functional Assessment of Cancer Therapy-General scale. The most frequently experienced symptom was fatigue, anguish was the most severe symptom-associated distress, and 28.9% of participants were clinically depressed. Factor analysis was used to identify symptom clusters based on the severity of patients' symptom experiences. Three symptom clusters were identified: treatment-associated, lung cancer and psychological symptom clusters. The regression model found a significant negative impact on QOL for depression and lung cancer symptom cluster. Age as the control variable was found to be significant impact on QOL. Therefore, psychological screening and appropriate intervention is an essential part of advanced cancer care. Both pharmacological and non-pharmacological approaches for alleviating depression may help to improve the QOL of lung cancer patients. © 2016 John Wiley & Sons Ltd.

Probiotics in early life: a preventative and treatment approach.

PubMed

Hashemi, Ashkan; Villa, Christopher R; Comelli, Elena M

2016-04-01

Microbial colonization of the infant gut plays a key role in immunological and metabolic pathways impacting human health. Since the maturation of the gut microbiota coincides with early life development, failure to develop a health compatible microbiota composition may result in pathology and disease in later life. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Maternal transfer of microorganisms is possible during pregnancy and lactation, and the mother's diet and microbiota can influence that of her offspring. Furthermore, pre-term birth, Caesarean section birth, formula feeding, antibiotic use, and malnutrition have been linked to dysbiosis, which in turn is associated with several pathologies such as necrotizing enterocolitis, inflammatory bowel diseases, antibiotic associated diarrhea, colic, and allergies. Thus, early life should represent a preferred stage of life for probiotic interventions. In this context, they could be regarded as a means to 'program' the individual for health maintenance, in order to prevent pathologies associated with dysbiosis. In order to elucidate the mechanisms underlying the benefits of probiotic administration, pre-clinical studies have been conducted and found an array of positive results such as improved microbial composition, intestinal maturation, decreased pathogenic load and infections, and improved immune response. Moreover, specific probiotic strains administered during the perinatal period have shown promise in attenuating severity of necrotizing enterocolitis. The mechanisms elucidated suggest that probiotic interventions in early life can be envisaged for disease prevention in both healthy offspring and offspring at risk of chronic disease.

Early-late life trade-offs and the evolution of ageing in the wild.

PubMed

Lemaître, Jean-François; Berger, Vérane; Bonenfant, Christophe; Douhard, Mathieu; Gamelon, Marlène; Plard, Floriane; Gaillard, Jean-Michel

2015-05-07

Empirical evidence for declines in fitness components (survival and reproductive performance) with age has recently accumulated in wild populations, highlighting that the process of senescence is nearly ubiquitous in the living world. Senescence patterns are highly variable among species and current evolutionary theories of ageing propose that such variation can be accounted for by differences in allocation to growth and reproduction during early life. Here, we compiled 26 studies of free-ranging vertebrate populations that explicitly tested for a trade-off between performance in early and late life. Our review brings overall support for the presence of early-late life trade-offs, suggesting that the limitation of available resources leads individuals to trade somatic maintenance later in life for high allocation to reproduction early in life. We discuss our results in the light of two closely related theories of ageing-the disposable soma and the antagonistic pleiotropy theories-and propose that the principle of energy allocation roots the ageing process in the evolution of life-history strategies. Finally, we outline research topics that should be investigated in future studies, including the importance of natal environmental conditions in the study of trade-offs between early- and late-life performance and the evolution of sex-differences in ageing patterns. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Early-Life Intelligence Predicts Midlife Biological Age

PubMed Central

Caspi, Avshalom; Belsky, Daniel W.; Harrington, Honalee; Houts, Renate; Israel, Salomon; Levine, Morgan E.; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Moffitt, Terrie E.

2016-01-01

Objectives: Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in “biological age”). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. Methods: We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Results: Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1–0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeconomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. Discussion: These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. PMID:26014827

Early evolution without a tree of life

PubMed Central

2011-01-01

Life is a chemical reaction. Three major transitions in early evolution are considered without recourse to a tree of life. The origin of prokaryotes required a steady supply of energy and electrons, probably in the form of molecular hydrogen stemming from serpentinization. Microbial genome evolution is not a treelike process because of lateral gene transfer and the endosymbiotic origins of organelles. The lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause. This article was reviewed by Dan Graur, W. Ford Doolittle, Eugene V. Koonin and Christophe Malaterre. PMID:21714942

TRIM28, a new molecular marker predicting metastasis and survival in early-stage non-small cell lung cancer.

PubMed

Liu, Lei; Zhao, Enhong; Li, Chunhui; Huang, Liang; Xiao, Lijun; Cheng, Luyang; Huang, Xu; Song, Youxin; Xu, Dawei

2013-02-01

TRIM28 is a universal corepressor for Kruppel-associated box zinc finger proteins. In this study, we demonstrated the expression of TRIM28 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < 0.001). TRIM28 knockdown resulted in a decrease in cell proliferation in liquid media as well as in soft agar. The proliferation rate was impaired and the cell cycle progression was inhibited after knockdown of TRIM28 in non-small cell lung cancer cell lines PAa and SK-MES-1. We used real-time polymerase chain reaction to detect circulating cancer cells in 138 non-small cell lung cancer patients. The overall positive detection rate was 30.4% (42 of 138) in peripheral blood of NSCLC patients and was 29.9% (29 of 97) in early-stage patients. In a 70-month follow-up study, 20 of 29 patients (69.0%) in TRIM28 positive group had recurrence and/or metastasis, significantly higher (P = 0.004) than in the TRIM28 negative group (25 of 68, 36.8%). In addition, non-small cell lung cancer patients whose circulating cancer cells expressed TRIM28 suffered shorter tumor-specific survival compared with those with absent TRIM28 expression (P < 0.001). Results of our study showed that TRIM28 provides a survival advantage to lung cancer cells and may be a new marker to predict metastasis and prognosis in early-stage non-small cell lung cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis.

PubMed

Kellett, Fiona; Robert, Niven M

2011-12-01

Sputum retention is a distressing feature of non-cystic fibrosis bronchiectasis and has been shown to contribute to the vicious cycle of infection seen in this disease. In a previous study we demonstrated that nebulised 7% hypertonic saline was both safe and effective in this patient population. Patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis, confirmed by HRCT, were entered into a randomised single blind cross-over study to evaluate 0.9% sodium chloride (IS) and 7% hypertonic saline (HS). Following a 4 week run in patients received a random order active HS or IS daily for 3 months. A 4 week wash-out phase was included between phases. We report lung function, quality of life, and health care utilisation responses. 32 patients mean age 56.6 years (SD 14.6), 16 male, were recruited of which 28 were randomised and completed the study. Lung function (%change from baseline) improved in HS vs. IS (FEV(1): 15.1, 1.8 p<0.01; FVC: 11.2, 0.7 p<0.01. SGRQ improved significantly from baseline (HS 6.0, IS 1.2; p<0.05). There were reductions in annualised antibiotic usage (HS 2.4, IS 5.4 courses per patient per year), annualised emergency health care utilisation visits were reduced (HS 2.1, IS 4.9 events per patient per year). There were also improvements in sputum viscosity and ease of expectoration (visual analogue scale). Regular use of 7% hypertonic saline improves lung function, quality of life and health care utilisation in non-cystic fibrosis bronchiectasis patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

Screening and Biosensor-Based Approaches for Lung Cancer Detection

PubMed Central

Wang, Lulu

2017-01-01

Early diagnosis of lung cancer helps to reduce the cancer death rate significantly. Over the years, investigators worldwide have extensively investigated many screening modalities for lung cancer detection, including computerized tomography, chest X-ray, positron emission tomography, sputum cytology, magnetic resonance imaging and biopsy. However, these techniques are not suitable for patients with other pathologies. Developing a rapid and sensitive technique for early diagnosis of lung cancer is urgently needed. Biosensor-based techniques have been recently recommended as a rapid and cost-effective tool for early diagnosis of lung tumor markers. This paper reviews the recent development in screening and biosensor-based techniques for early lung cancer detection. PMID:29065541

Impact of early life adversity on EMG stress reactivity of the trapezius muscle.

PubMed

Luijcks, Rosan; Vossen, Catherine J; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J; Lousberg, Richel

2016-09-01

Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies.

Early life permethrin exposure leads to hypervitaminosis D, nitric oxide and catecholamines impairment.

PubMed

Fedeli, Donatella; Carloni, Manuel; Nasuti, Cinzia; Gambini, Anna; Scocco, Vitangelo; Gabbianelli, Rosita

2013-09-01

The aim of this study is to gain more knowledge on the impact of early life pesticide exposure on premature aging. The effect of a low dose of the insecticide permethrin administered to rats during early life (1/50 LD50, from 6th to 21st day of life) was analyzed by measuring some metabolites in plasma and urine of 500-day-old animals. Significant differences in early life treated rats compared to the control group were found in the plasma levels of Ca(++), Na(+), 25-hydroxy-vitamin D, adrenaline, noradrenaline, nitric oxide, cholesterol and urea while in urine only Na(+) content was different. These results add information on the impact of permethrin during the neonatal period, supporting the evidence that early life environmental exposure to xenobiotics has long-term effects, inducing modifications in adulthood that can be revealed by the analysis of some macroelements, metabolites and catecholamines in plasma, when rats are 500 days old. Copyright © 2013 Elsevier Inc. All rights reserved.

The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

PubMed Central

Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

2015-01-01

Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

EARLY LIFE RISKS, ANTISOCIAL TENDENCIES, AND PRETEEN DELINQUENCY.

PubMed

Staff, Jeremy; Whichard, Corey; Siennick, Sonja; Maggs, Jennifer

2015-11-01

Early age-of-onset delinquency and substance use confer a major risk for continued criminality, alcohol and drug abuse, and other serious difficulties throughout the life course. Our objective is to examine the developmental roots of preteen delinquency and substance use. Using nationally representative longitudinal data from the UK Millennium Cohort Study ( n = 13,221), we examine the influence of early childhood developmental and family risks on latent pathways of antisocial tendencies from ages 3 to 7, and the influence of those pathways on property crime and substance use by age 11. We identified a normative, non-antisocial pathway; a pathway marked by oppositional behavior and fighting; a pathway marked by impulsivity and inattention; and a rare pathway characterized by a wide range of antisocial tendencies. Children with developmental and family risks that emerged by age 3-specifically difficult infant temperament, low cognitive ability, weak parental closeness, and disadvantaged family background-face increased odds of antisocial tendencies. There is minimal overlap between the risk factors for early antisocial tendencies and those for preteen delinquency. Children on an antisocial pathway are more likely to engage in preteen delinquency and substance use by age 11, even after accounting for early life risk factors.

EARLY LIFE RISKS, ANTISOCIAL TENDENCIES, AND PRETEEN DELINQUENCY*

PubMed Central

Staff, Jeremy; Whichard, Corey; Siennick, Sonja; Maggs, Jennifer

2015-01-01

Early age-of-onset delinquency and substance use confer a major risk for continued criminality, alcohol and drug abuse, and other serious difficulties throughout the life course. Our objective is to examine the developmental roots of preteen delinquency and substance use. Using nationally representative longitudinal data from the UK Millennium Cohort Study (n = 13,221), we examine the influence of early childhood developmental and family risks on latent pathways of antisocial tendencies from ages 3 to 7, and the influence of those pathways on property crime and substance use by age 11. We identified a normative, non-antisocial pathway; a pathway marked by oppositional behavior and fighting; a pathway marked by impulsivity and inattention; and a rare pathway characterized by a wide range of antisocial tendencies. Children with developmental and family risks that emerged by age 3—specifically difficult infant temperament, low cognitive ability, weak parental closeness, and disadvantaged family background—face increased odds of antisocial tendencies. There is minimal overlap between the risk factors for early antisocial tendencies and those for preteen delinquency. Children on an antisocial pathway are more likely to engage in preteen delinquency and substance use by age 11, even after accounting for early life risk factors. PMID:26900167

Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

PubMed

Humphreys, Kathryn L; Kircanski, Katharina; Colich, Natalie L; Gotlib, Ian H

2016-10-01

Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems. In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist. High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems. Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning. © 2016 Association for Child and Adolescent Mental Health.

Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

PubMed

Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

2017-09-15

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P < 0.0001) and intraoperative Pe ( P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.

PubMed

Lieberman, Richard; Armeli, Stephen; Scott, Denise M; Kranzler, Henry R; Tennen, Howard; Covault, Jonathan

2016-09-01

Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T-allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Photodynamic therapy of early stage cancer of lung, esophagus, and stomach with two different photosensitizers

NASA Astrophysics Data System (ADS)

Chissov, Valery I.; Sokolov, Victor V.; Trakhtenberg, A. K.; Mamontov, A. S.; Vaschakmadze, L. A.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Belous, T. A.; Gladunov, V. K.; Aristarkhova, E. I.; Zharkova, Natalia N.; Menenkov, V. D.

1996-01-01

The paper presents the results of photodynamic therapy (PDT) of early-stage cancer of lung (17 patients), esophagus (8 patients) and stomach (10 patients). Fifteen patients had second primary tumors. New drugs photoheme and photosens were used as photosensitizers. Complete remission was obtained in 87%. The patients are followed up without relapses to 2.5 years.

Identification of early-stage usual interstitial pneumonia from low-dose chest CT scans using fractional high-density lung distribution

NASA Astrophysics Data System (ADS)

Xie, Yiting; Salvatore, Mary; Liu, Shuang; Jirapatnakul, Artit; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

2017-03-01

A fully-automated computer algorithm has been developed to identify early-stage Usual Interstitial Pneumonia (UIP) using features computed from low-dose CT scans. In each scan, the pre-segmented lung region is divided into N subsections (N = 1, 8, 27, 64) by separating the lung from anterior/posterior, left/right and superior/inferior in 3D space. Each subsection has approximately the same volume. In each subsection, a classic density measurement (fractional high-density volume h) is evaluated to characterize the disease severity in that subsection, resulting in a feature vector of length N for each lung. Features are then combined in two different ways: concatenation (2*N features) and taking the maximum in each of the two corresponding subsections in the two lungs (N features). The algorithm was evaluated on a dataset consisting of 51 UIP and 56 normal cases, a combined feature vector was computed for each case and an SVM classifier (RBF kernel) was used to classify them into UIP or normal using ten-fold cross validation. A receiver operating characteristic (ROC) area under the curve (AUC) was used for evaluation. The highest AUC of 0.95 was achieved by using concatenated features and an N of 27. Using lung partition (N = 27, 64) with concatenated features had significantly better result over not using partitions (N = 1) (p-value < 0.05). Therefore this equal-volume partition fractional high-density volume method is useful in distinguishing early-stage UIP from normal cases.

Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

PubMed

Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

2017-05-01

Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

Life Satisfaction in Early Adolescence: Personal, Neighborhood, School, Family, and Peer Influences

ERIC Educational Resources Information Center

Oberle, Eva; Schonert-Reichl, Kimberly A.; Zumbo, Bruno D.

2011-01-01

Drawing from an ecological assets framework as well as research and theory on positive youth development, this study examined the relationship of early adolescents' satisfaction with life to trait optimism and assets representing the social contexts in which early adolescents spend most of their time. Self-reports of satisfaction with life,…

A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.

PubMed

Gunatilake, Samal; Brims, Fraser J H; Fogg, Carole; Lawrie, Iain; Maskell, Nick; Forbes, Karen; Rahman, Najib; Morris, Steve; Ogollah, Reuben; Gerry, Stephen; Peake, Mick; Darlison, Liz; Chauhan, Anoop J

2014-09-19

Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant

Potential application of non-small cell lung cancer-associated autoantibodies to early cancer diagnosis

PubMed Central

Yao, Yibing; Fan, Yu; Wu, Jun; Wan, Haisu; Wang, Jing; Lam, Stephen; Lam, Wan L.; Girard, Luc; Gazdar, Adi F.; Wu, Zhihao; Zhou, Qinghua

2015-01-01

To identify a panel of tumor associated autoantibodies which can potentially be used as biomarkers for the early diagnosis of non-small cell lung cancer (NSCLC). Thirty-five unique and in-frame expressed phage proteins were isolated. Based on the gene expression profiling, four proteins were selected for further study. Both receiver operating characteristic curve analysis and leave-one-out method revealed that combined measurements of four antibodies produced have better predictive accuracies than any single marker alone. Leave-one-out validation also showed significant relevance with all stages of NSCLC patients. The panel of autoantibodies has a high potential for detecting early stage NSCLC. PMID:22713465

The die is cast: arsenic exposure in early life and disease susceptibility.

PubMed

Thomas, David J

2013-12-16

Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

The Changing Life Space of Early Adolescence.

ERIC Educational Resources Information Center

Larson, Reed, Ed.; Richards, Maryse, H., Ed.

1989-01-01

Eight papers are presented that describe the daily experience of White American children in grades 5 through 9. Each paper examines a segment of daily activity (e.g., schoolwork, talking, sports) and the associated affective states for 401 participants to provide a picture of the life space of early adolescence. (SLD)

Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

PubMed

Shiroyama, Takayuki; Suzuki, Hidekazu; Tamiya, Motohiro; Tamiya, Akihiro; Tanaka, Ayako; Okamoto, Norio; Nakahama, Kenji; Taniguchi, Yoshihiko; Isa, Shun-Ichi; Inoue, Takako; Imamura, Fumio; Atagi, Shinji; Hirashima, Tomonori

2018-01-01

Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil-to-lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44-5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

PubMed

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational