Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary ...hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema.
We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization.
In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm(2) (CSA(<5)) and 5 to 10 mm(2) (CSA(5-10)), and calculated the percentage of total CSA for the lung area (%CSA(<5) and %CSA(5-10), respectively). The correlations of %CSA(<5) and %CSA(5-10) with pulmonary arterial mean pressure (Ppa) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using Ppa as the dependent outcome was also performed.
The %CSA(<5) had a significant negative correlation with Ppa (r = -0.512, P < 0.0001), whereas the correlation between %CSA(5-10) and Ppa did not reach statistical significance (r = -0.196, P = 0.083). Multiple linear regression analysis showed that %CSA(<5) and diffusing capacity of carbon monoxide (DL(CO)) % predicted were independent predictors of Ppa (r(2) = 0.541): %CSA (<5) (P < 0.0001), and DL(CO) % predicted (P = 0.022).
The %CSA(<5) measured on CT images is significantly correlated to Ppa in severe emphysema and can estimate the degree of pulmonary hypertension.
Due to their relatively homogeneous lifestyle and living environment, the Amish offer a novel opportunity to study the health associations of tobacco smoke exposure, particularly secondhand smoke. We ...hypothesized that secondhand smoke exposure is associated with worse pulmonary and cardiometabolic health. We examined cross-sectional data on 3568 Amish study participants, including tobacco use and secondhand smoke exposure from family members included in the study. Thirty-four percent of Amish men reported ever smoking. Of this proportion, 64% used cigars, 46% cigarettes, and 21% pipes. Less than 1% of women reported ever smoking. Smoking was associated with lower spirometric lung function, higher body mass index, lower HDL cholesterol, higher heart rate, lower ankle-brachial index, and larger aortic diameter in men. A greater number of sources of secondhand smoke exposure (defined from the total of spouses, parents, and siblings who smoke) was associated with higher body mass index (p = 0.03) and with higher fasting glucose in men (p = 0.01), but not in women (p = 0.007 for sex*secondhand smoke interaction). Secondhand smoke exposure was also associated with reduced HDL cholesterol only in women (p = 0.002) and a lower heart rate only in men (p = 0.006). Smoking habits among the Old Order Amish are notable for the absence of female participation and a high proportion of cigar and pipe use. Smoking is associated with decreased spirometric indices of lung function and increased cardiovascular risk in this population and secondhand smoke exposure is associated with a greater burden of risk factors for cardiovascular disease. Sex differences in correlations could reflect differences in exposure patterns, mechanisms, or susceptibilities.
In patients with emphysema being evaluated for lung volume reduction surgery, Doppler echocardiography has been used to screen for pulmonary hypertension as an indicator of increased peri-operative ...risk. To determine the accuracy of this test, the present authors compared the results of right heart catheterisations and Doppler echocardiograms in 163 patients participating in the cardiovascular substudy of the National Emphysema Treatment Trial. Substudy patients had both catheterisation and Doppler echocardiography performed before and after randomisation. In 74 paired catheterisations and echocardiograms carried out on 63 patients, the mean values of invasively measured pulmonary artery systolic pressures and the estimated right ventricular systolic pressures were similar. However, using the World Health Organization's definitions of pulmonary hypertension, echocardiography had a sensitivity of 60%, specificity of 74%, positive predictive value of 68% and a negative predictive value of 67% compared with the invasive measurement. Bland-Altman analysis revealed a bias of 0.37 kPa with 95% limits of agreement from -2.5-3.2 kPa. In patients with severe emphysema, echocardiographic estimates of pulmonary artery pressures correlate very weakly with right heart catheterisations, and the test characteristics (e.g. sensitivity, specificity, etc.) of echocardiographic assessments are poor.
Asthma and COPD can significantly affect patients and pose a substantial economic burden for both patients and managed-care plans. This study compares utilization outcomes in patients with asthma, ...COPD, or co-occurring asthma and COPD in a Medicaid population, and assesses the incremental burden of COPD in patients with asthma.
We queried medical claims of Medicaid patients aged 40 to 64 years with asthma and/or COPD filed between January 1, 2001, and December 31, 2003, from encounter data. COPD patients were identified based on at least one claim with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes 491, 492, 496; and asthma patients were identified on the basis of ICD-9 code 493 as diagnosis. We analyzed annual utilization and cost of hospitalizations, physician, and outpatient services attributable to asthma and/or COPD.
The analysis included a total of 3,072 asthma, 3,455 COPD, and 2,604 COPD/asthma patients. COPD/asthma co-occurring disease has higher utilization of any service type than either disease alone. Compared with asthma patients, COPD patients were 16% and 51% more likely to use physician (odds ratio OR, 1.16; 95% confidence interval CI, 1.01 to 1.34) and inpatient services (OR, 1.51; 95% CI, 1.31 to 1.74), respectively; and 60% less likely to use outpatient services (OR, 0.40; 95% CI, 0.35 to 0.46). Compared with asthma patients, COPD patients and COPD/asthma co-occurring patients cost 50% (OR, 1.50; 95% CI, 1.3 to 1.74) and five times (OR, 5.25; 95% CI, 4.59 to 6.02) more for total medical services, respectively.
Our data suggest that patients with COPD and co-occurring COPD/asthma were sicker and used more medical services than asthma patients. The incremental burden of COPD to patients with asthma is significant.
cDNAs encoding two gut laccase isoforms (
RfLacA and
RfLacB) were sequenced from the termite
Reticulitermes flavipes. Phylogenetic analyses comparing translated
R. flavipes laccases to 67 others from ...prokaryotes and eukaryotes indicate that the
R. flavipes laccases are evolutionarily unique. Alignments with crystallography-verified laccases confirmed that peptide motifs involved in metal binding are 100% conserved in both isoforms. Laccase transcripts and phenoloxidase activity were most abundant in symbiont-free salivary gland and foregut tissue, verifying that the genes and activities are host-derived. Using a baculovirus-insect expression system, the two isoforms were functionally expressed with histidine tags and purified to near homogeneity. ICP-MS (inductively coupled plasma – mass spectrometry) analysis of RfLacA identified bound metals consisting mainly of copper (∼4 copper molecules per laccase protein molecule and ∼3 per histidine tag) with lesser amounts of calcium, manganese and zinc. Both recombinant enzyme preparations showed strong activity towards the lignin monomer sinapinic acid and four other phenolic substrates. By contrast, both isoforms displayed much lower or no activity against four melanin precursors, suggesting that neither isoform is involved in integument formation. Modification of lignin alkali by the recombinant RfLacA preparation was also observed. These findings provide evidence that
R. flavipes gut laccases are evolutionarily distinct, host-derived, produced in the salivary gland, secreted into the foregut, bind copper, and play a role in lignocellulose digestion. These findings contribute to a better understanding of termite digestion and gut physiology, and will assist future translational studies that examine the contributions of individual termite enzymes in lignocellulose digestion.
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►Coy et al. Termite gut laccases were observed to catalyze a wide range phenoloxidase reactions, but contrary to insect cuticular laccases, they are more active towards phenolic and mono-lignol substrates than melanin precursors.
Plant quality can shape plant–insect interactions and plant secondary metabolites are known to play an influential role in mediating these interactions. Cannabinoids are a group of terpenophenolic ...compounds in
Cannabis
that have demonstrated negative effects on insect herbivores, yet specific mechanisms are currently not well understood. Insects can modulate their rate of growth, food intake, or production of frass (i.e., insect feces) to mitigate consumption of a diet with poor nutritional quality. Detoxification and nutritional enzymes are essential in performing these functions. To test how cannabinoids impact insect performance and enzymatic activity, we performed no-choice feeding bioassays on fall armyworm (
Spodoptera frugiperda
) with artificial diet spiked with different concentrations of CBD and measured fall armyworm growth, consumption, and frass production and analyzed detoxification and nutritional enzyme activities. We found that as CBD concentration increased fall armyworm growth and consumption decreased, but found no impact on digestibility or conversion efficiencies. Results from the enzymatic assays varied, but CYP450 and protease activity decreased, while glucosidase activity increased, as CBD concentration increased. Relationships among enzyme activities suggest that a reduction in protease activity might limit a detoxification response, by limiting amino acid availability needed for detoxification enzyme production, even though energy collection activity, via increased glucosidase activity, occurred. These outcomes suggest specific mechanisms by which CBD has a negative influence on insect herbivore performance.
Fibrotic scarring drives the progression of heart failure after myocardial infarction (MI). Therefore, the development of specific treatment regimens to counteract fibrosis is of high clinical ...relevance. The transcription factor SOX9 functions as an important regulator during embryogenesis, but recent data point towards an additional causal role in organ fibrosis. We show here that SOX9 is upregulated in the scar after MI in mice. Fibroblast specific deletion of Sox9 ameliorated MI-induced left ventricular dysfunction, dilatation and myocardial scarring in vivo. Unexpectedly, deletion of Sox9 also potently eliminated persisting leukocyte infiltration of the scar in the chronic phase after MI. RNA-sequencing from the infarct scar revealed that Sox9 deletion in fibroblasts resulted in strongly downregulated expression of genes related to extracellular matrix, proteolysis and inflammation. Importantly, Sox9 deletion in isolated cardiac fibroblasts in vitro similarly affected gene expression as in the cardiac scar and reduced fibroblast proliferation, migration and contraction capacity. Together, our data demonstrate that fibroblast SOX9 functions as a master regulator of cardiac fibrosis and inflammation and might constitute a novel therapeutic target during MI.
Throughout the industrialized world, nearly one in five employees works some form of nontraditional shift. Such shift work is associated with numerous negative health consequences, ranging from ...cognitive complaints to cancer, as well as diminished quality of life. Furthermore, a substantial percentage of shift workers develop shift work disorder, a circadian rhythm sleep disorder characterized by excessive sleepiness, insomnia, or both as a result of shift work. In addition to adverse health consequences and diminished quality of life at the individual level, shift work disorder incurs significant costs to employers through diminished workplace performance and increased accidents and errors. Nonetheless, shift work will remain a vital component of the modern economy. This article reviews seminal and recent literature regarding shift work, with an eye toward real-world application in clinical and organizational settings.
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