Disproportionally Impaired Diffusion Capacity Relative to Airflow Limitation in COPD

Forced expiratory volume in 1 s (FEV₁) is a standard physiological index of chronic obstructive pulmonary disease (COPD), but reflects emphysema and vascular abnormalities less sensitively than diffusion capacity for carbon monoxide (D_LCO). This study tested whether a disproportionally impaired D_LCO relative to FEV₁ (FEV₁ z-score>-3 and D_LCO z-score≤-3) is a common functional COPD phenotype associated with distinct clinical and structural features and the prognosis of two cohorts. The cross-sectional analyses of the Korea COPD Subgroup Study (KOCOSS) cohort (multicenter study in Korea) included 743 males with COPD whose D_LCO was available. The cross-sectional and longitudinal analyses of the Kyoto University Cohort (single-center study in Japan) included 195 males with COPD who were prospectively followed for 10 years. A disproportionally impaired D_LCO relative to FEV₁ was observed in 29% and 31% of patients in the KOCOSS and Kyoto University cohorts, respectively. In the multivariable analysis, the disproportionally impaired D_LCO was associated with worse symptoms, shorter 6-minute walking distance, paraseptal and centrilobular emphysema on computed tomography, and reduced arterial oxygen and carbon dioxide pressures compared to the reference (FEV₁ z-score>-3 and D_LCO z-score>-3). In the multivariable Cox proportional hazard model, a higher long-term mortality was observed in the disproportionally impaired D_LCO group than in the reference group (hazard ratio [95% confidence interval] = 3.09 [1.52–6.29]) and similar to the D_LCO z-score≤-3 and FEV₁ z-score≤-3 group. The disproportionally impaired D_LCO relative to FEV₁ is common and associated with increased symptoms, emphysema, arterial blood gas abnormalities, and increased long-term mortality in patients with COPD

Evaluation of Reperfused Myocardial Infarction by Low-Dose Multidetector Computed Tomography Using Prospective Electrocardiography (ECG)-Triggering: Comparison with Magnetic Resonance Imaging

PURPOSE: To evaluate the potential of prospective electrocardiography (ECG)- gated 64-slice multidetector computed tomography (MDCT) for evaluation of myocardial enhancement, infarct size, and stent patency after percutaneous coronary intervention (PCI) with stenting in patients with myocardial infarction. MATERIALS AND METHODS: Seventeen patients who were admitted with acute myocardial infarction were examined with prospective ECG-gated 64-slice cardiac MDCT and magnetic resonance (MR) imaging after reperfusion using PCI with stenting. Cardiac MDCT was performed with two different phases: arterial and delayed phases. We evaluated the stent patency on the arterial phase, and nonviable myocardium on the delayed phase of computed tomography (CT) image, and they were compared with the results from the delayed MR images. RESULTS: Total mean radiation dose was 7.7 +/- 0.5 mSv on the two phases of CT images. All patients except one showed good patency of the stent at the culprit lesion on the arterial phase CT images. All patients had hyperenhanced area on the delayed phase CT images, which correlated well with those on the delayed phase MR images, with a mean difference of 1.6% (20 +/- 10% vs. 22 +/- 10%, r = 0.935, p = 0.10). Delayed MR images had a better contrast-to-noise ratio (CNR) than delayed CT images (27.1 +/- 17.8% vs. 4.3 +/- 2.1%, p < 0.001). CONCLUSION: Prospective ECG-gated 64-slice MDCT provides the potential to evaluate myocardial viability on delayed phase as well as for stent patency on arterial phase with an acceptable radiation dose after PCI with stenting in patients with myocardial infarctionope

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays

Background Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma. Methods After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features. Results CD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013). Conclusions This study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma

Characterization of a Human Cell Line Stably Over-Expressing the Candidate Oncogene, Dual Specificity Phosphatase 12

Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12). While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1) which is implicated in metastasis.Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted

Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism

Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of “emergency” granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis

Metabolomic and transcriptomic analysis of the rice response to the bacterial blight pathogen Xanthomonas oryzae pv. oryzae

Bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv. oryzae (Xoo), gives rise to devastating crop losses in rice. Disease resistant rice cultivars are the most economical way to combat the disease. The TP309 cultivar is susceptible to infection by Xoo strain PXO99. A transgenic variety, TP309_Xa21, expresses the pattern recognition receptor Xa21, and is resistant. PXO99△raxST, a strain lacking the raxST gene, is able to overcome Xa21-mediated immunity. We used a single extraction solvent to demonstrate comprehensive metabolomics and transcriptomics profiling under sample limited conditions, and analyze the molecular responses of two rice lines challenged with either PXO99 or PXO99△raxST. LC–TOF raw data file filtering resulted in better within group reproducibility of replicate samples for statistical analyses. Accurate mass match compound identification with molecular formula generation (MFG) ranking of 355 masses was achieved with the METLIN database. GC–TOF analysis yielded an additional 441 compounds after BinBase database processing, of which 154 were structurally identified by retention index/MS library matching. Multivariate statistics revealed that the susceptible and resistant genotypes possess distinct profiles. Although few mRNA and metabolite differences were detected in PXO99 challenged TP309 compared to mock, many differential changes occurred in the Xa21-mediated response to PXO99 and PXO99△raxST. Acetophenone, xanthophylls, fatty acids, alkaloids, glutathione, carbohydrate and lipid biosynthetic pathways were affected. Significant transcriptional induction of several pathogenesis related genes in Xa21 challenged strains, as well as differential changes to GAD, PAL, ICL1 and Glutathione-S-transferase transcripts indicated limited correlation with metabolite changes under single time point global profiling conditions

Population genomics of marine zooplankton

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Bucklin, Ann et al. "Population Genomics of Marine Zooplankton." Population Genomics: Marine Organisms. Ed. Om P. Rajora and Marjorie Oleksiak. Springer, 2018. doi:10.1007/13836_2017_9.The exceptionally large population size and cosmopolitan biogeographic distribution that distinguish many – but not all – marine zooplankton species generate similarly exceptional patterns of population genetic and genomic diversity and structure. The phylogenetic diversity of zooplankton has slowed the application of population genomic approaches, due to lack of genomic resources for closelyrelated species and diversity of genomic architecture, including highly-replicated genomes of many crustaceans. Use of numerous genomic markers, especially single nucleotide polymorphisms (SNPs), is transforming our ability to analyze population genetics and connectivity of marine zooplankton, and providing new understanding and different answers than earlier analyses, which typically used mitochondrial DNA and microsatellite markers. Population genomic approaches have confirmed that, despite high dispersal potential, many zooplankton species exhibit genetic structuring among geographic populations, especially at large ocean-basin scales, and have revealed patterns and pathways of population connectivity that do not always track ocean circulation. Genomic and transcriptomic resources are critically needed to allow further examination of micro-evolution and local adaptation, including identification of genes that show evidence of selection. These new tools will also enable further examination of the significance of small-scale genetic heterogeneity of marine zooplankton, to discriminate genetic “noise” in large and patchy populations from local adaptation to environmental conditions and change.Support was provided by the US National Science Foundation to AB and RJO (PLR-1044982) and to RJO (MCB-1613856); support to IS and MC was provided by Nord University (Norway)

Heterogeneity and changes in preferences for dying at home:a systematic review

Background Home-based models of hospice and palliative care are promoted with the argument that most people prefer to die at home. We examined the heterogeneity in preferences for home death and explored, for the first time, changes of preference with illness progression. Methods We searched for studies on adult preferences for place of care at the end of life or place of death in MEDLINE (1966-2011), EMBASE (1980-2011), psycINFO (1967-2011), CINAHL (1982-2011), six palliative care journals (2006-11) and reference lists. Standard criteria were used to grade study quality and evidence strength. Scatter plots showed the percentage preferring home death amongst patients, lay caregivers and general public, by study quality, year, weighted by sample size. Results 210 studies reported preferences of just over 100,000 people from 33 countries, including 34,021 patients, 19,514 caregivers and 29,926 general public members. 68% of studies with quantitative data were of low quality; only 76 provided the question used to elicit preferences. There was moderate evidence that most people prefer a home death-this was found in 75% of studies, 9/14 of those of high quality. Amongst the latter and excluding outliers, home preference estimates ranged 31% to 87% for patients (9 studies), 25% to 64% for caregivers (5 studies), 49% to 70% for the public (4 studies). 20% of 1395 patients in 10 studies (2 of high quality) changed their preference, but statistical significance was untested. Conclusions Controlling for methodological weaknesses, we found evidence that most people prefer to die at home. Around four fifths of patients did not change preference as their illness progressed. This supports focusing on home-based care for patients with advanced illness yet urges policy-makers to secure hospice and palliative care elsewhere for those who think differently or change their mind. Research must be clear on how preferences are elicited. There is an urgent need for studies examining change of preferences towards death

Enzyme production from food wastes using a biorefinery concept

According to Food and Agricultural Organization (FAO), one-third of food produced globally for human consumption (nearly 1.3 billion tonnes) is lost along the food supply chain. In many countries food waste is currently landfilled or incinerated together with other combustible municipal wastes for possible recovery of energy. However, these two options are facing more and more economic and environmental stresses. Due to its organic- and nutrient-rich nature, theoretically food waste can be converted to valuable products (e.g. bio-products such as methane, hydrogen, ethanol, enzymes, organic acids, chemicals and fuels) through various fermentation processes. Such conversion of food waste is potentially more profitable than its conversion to animal feed or transportation fuel. Food waste valorisation has therefore gained interest, with value added bio-products such as methane, hydrogen, ethanol, enzymes, organic acids, chemicals, and fuels. Therefore, the aim of this review is to provide information on the food waste situation with emphasis on Asia–Pacific countries and the state of the art food waste processing technologies to produce enzymes