Computer-assisted determination of left ventricular endocardial borders reduces variability in the echocardiographic assessment of ejection fraction

Background

Left ventricular size and function are important prognostic factors in heart disease. Their measurement is the most frequent reason for sending patients to the echo lab. These measurements have important implications for therapy but are sensitive to the skill of the operator. Earlier automated echo-based methods have not become widely used. The aim of our study was to evaluate an automatic echocardiographic method (with manual correction if needed) for determining left ventricular ejection fraction (LVEF) based on an active appearance model of the left ventricle (syngo^®AutoEF, Siemens Medical Solutions). Comparisons were made with manual planimetry (manual Simpson), visual assessment and automatically determined LVEF from quantitative myocardial gated single photon emission computed tomography (SPECT).

Methods

60 consecutive patients referred for myocardial perfusion imaging (MPI) were included in the study. Two-dimensional echocardiography was performed within one hour of MPI at rest. Image quality did not constitute an exclusion criterion. Analysis was performed by five experienced observers and by two novices.

Results

LVEF (%), end-diastolic and end-systolic volume/BSA (ml/m²) were for uncorrected AutoEF 54 ± 10, 51 ± 16, 24 ± 13, for corrected AutoEF 53 ± 10, 53 ± 18, 26 ± 14, for manual Simpson 51 ± 11, 56 ± 20, 28 ± 15, and for MPI 52 ± 12, 67 ± 26, 35 ± 23. The required time for analysis was significantly different for all four echocardiographic methods and was for uncorrected AutoEF 79 ± 5 s, for corrected AutoEF 159 ± 46 s, for manual Simpson 177 ± 66 s, and for visual assessment 33 ± 14 s. Compared with the expert manual Simpson, limits of agreement for novice corrected AutoEF was lower than for novice manual Simpson (0.8 ± 10.5 vs. -3.2 ± 11.4 LVEF percentage points). Calculated for experts and with LVEF (%) categorized into < 30, 30–44, 45–54 and ≥ 55, kappa measure of agreement was moderate (0.44–0.53) for all method comparisons (uncorrected AutoEF not evaluated).

Conclusion

Corrected AutoEF reduces the variation in measurements compared with manual planimetry, without increasing the time required. The method seems especially suited for unexperienced readers.     

Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair

Chromosome stability depends on accurate chromosome segregation and efficient DNA double-strand break (DSB) repair. Sister chromatid cohesion, established during S phase by the protein complex cohesin, is central to both processes. In the absence of cohesion, chromosomes missegregate and G2-phase DSB repair fails. Here, we demonstrate that G2-phase repair also requires the presence of cohesin at the damage site. Cohesin components are shown to be recruited to extended chromosome regions surrounding DNA breaks induced during G2. We find that in the absence of functional cohesin-loading proteins (Scc2/Scc4), the accumulation of cohesin at DSBs is abolished and repair is defective, even though sister chromatids are connected by S phase generated cohesion. Evidence is also provided that DSB induction elicits establishment of sister chromatid cohesion in G2, implicating that damage-recruited cohesin facilitates DNA repair by tethering chromatids.     

Greenhouse gas emissions and global warming potential of traditional and diversified tropical rice rotation systems

Global rice agriculture will be increasingly challenged by water scarcity, while at the same time changes in demand (e.g. changes in diets or increasing demand for biofuels) will feed back on agricultural practices. These factors are changing traditional cropping patterns from double‐rice cropping to the introduction of upland crops in the dry season. For a comprehensive assessment of greenhouse gas (GHG) balances, we measured methane (CH₄)/nitrous oxide (N₂O) emissions and agronomic parameters over 2.5 years in double‐rice cropping (R‐R) and paddy rice rotations diversified with either maize (R‐M) or aerobic rice (R‐A) in upland cultivation. Introduction of upland crops in the dry season reduced irrigation water use and CH₄ emissions by 66–81% and 95–99%, respectively. Moreover, for practices including upland crops, CH₄ emissions in the subsequent wet season with paddy rice were reduced by 54–60%. Although annual N₂O emissions increased two‐ to threefold in the diversified systems, the strong reduction in CH₄ led to a significantly lower (P < 0.05) annual GWP (CH₄ + N₂O) as compared to the traditional double‐rice cropping system. Measurements of soil organic carbon (SOC) contents before and 3 years after the introduction of upland crop rotations indicated a SOC loss for the R‐M system, while for the other systems SOC stocks were unaffected. This trend for R‐M systems needs to be followed as it has significant consequences not only for the GWP balance but also with regard to soil fertility. Economic assessment showed a similar gross profit span for R‐M and R‐R, while gross profits for R‐A were reduced as a consequence of lower productivity. Nevertheless, regarding a future increase in water scarcity, it can be expected that mixed lowland–upland systems will expand in SE Asia as water requirements were cut by more than half in both rotation systems with upland crops.     

Distribution of melatonin MT1 receptor immunoreactivity in human retina.

Melatonin is synthesized in the pineal gland and retina during the night. Retinal melatonin is believed to be involved in local cellular modulation and in regulation of light-induced entrainment of circadian rhythms. The present study provides the first immunohistochemical evidence for the localization of melatonin 1a-receptor (MT1) in human retina of aged subjects. Ganglion, amacrine, and photoreceptor cells expressed MT1. In addition, MT1 immunoreactivity was localized to cell processes in the inner plexiform layer and to central vessels of the retina, as well as to retinal vessels but not to ciliary or choroidal vessels. These results support a variety of cellular and vascular effects of melatonin in the human retina. Preliminary evidence from patients with Alzheimer's disease (AD) revealed increased MT1 immunoreactivity in ganglion and amacrine cells, as well as in vessels. In AD cases photoreceptor cells were degenerated and showed low MT1 expression.     

Effects after inhalation of (1-->3)-beta-D-glucan and relation to mould exposure in the home

BACKGROUND: Damp conditions indoors favour the growth of microorganisms, and these contain several agents that may cause inflammation when inhaled. Moulds contain a polyglucose in their cell wall, defined as (1-->3)-beta-D-glucan, exhibiting effects on inflammatory cells. AIM: The aim of the present study was to evaluate whether an inhalation challenge to purified (1-->3)-beta-D-glucan (grifolan) in humans could induce effects on inflammatory markers in blood, and to evaluate whether the reactions were related to the home exposure to (1-->3)-beta-D-glucan. METHODS: Seventeen subjects in homes with high levels of airborne (1-->3)-beta-D-glucan (G-high) and 18 subjects in homes with low levels of (1-->3)-beta-D-glucan (G-low) underwent two randomised, double-blind inhalation challenges, one to (1-->3)-beta-D-glucan suspended in saline and one to saline alone. A blood sample was taken before and after the challenges, and differential cell count, granulocyte enzymes in serum and the secretion of cytokines from peripheral blood mononuclear cells (PBMC) were measured. RESULTS: Inhalation challenge with (1-->3)-beta-D-glucan induced a decrease in the secretion of tumour necrosis factor alpha from endotoxin-stimulated PBMC in the G-high group as well as in the G-low group. In the G-high group, the inhalation of (1-->3)-beta-D-glucan induced an increase in blood lymphocytes that was significantly different from the saline-induced effect. CONCLUSIONS: The results suggest that an inhalation challenge to (1-->3)-beta-D-glucan has an effect on inflammatory cells and this effect may be related to a chronic exposure to moulds at home.     

rbcL sequences support exclusion ofRetzia,Desfontainia, andNicodemia from theGentianales

The taxonomic positions ofRetzia, Desfontainia, andNicodemia have been much discussed, and all three genera have been included inLoganiaceae (Gentianales). We have made a cladistic analysis ofrbcL gene sequences to determine the relationships of these taxa toGentianales. Four newrbcL sequences are presented; i.e., ofRetzia, Desfontainia, Diervilla (Caprifoliaceae), andEuthystachys (Stilbaceae). Our results show thatRetzia, Desfontainia, andNicodemia are not closely related toLoganiaceae or theGentianales. Retzia is most closely related toEuthystachys and is better included inStilbaceae. The positions ofDesfontainia andNicodemia are not settled, butDesfontainia shows affinity for theDipsacales s.l. andNicodemia for theLamiales s.l.     

Hypothermic protection of the ischemic heart via alterations in apoptotic pathways as assessed by gene array analysis.

Hypothermia improves resistance to ischemia in the cardioplegia-arrested heart. This adaptive process produces changes in specific signaling pathways for mitochondrial proteins and heat-shock response. To further test for hypothermic modulation of other signaling pathways such as apoptosis, we used various molecular techniques, including cDNA arrays. Isolated rabbit hearts were perfused and exposed to ischemic cardioplegic arrest for 2 h at 34 degrees C [ischemic group (I); n = 13] or at 30 degrees C before and during ischemia [hypothermic group (H); n = 12]. Developed pressure, the maximum first derivative of left ventricular pressure, oxygen consumption, and pressure-rate product (P < 0.05) recovery were superior in H compared with in I during reperfusion. mRNA expression for the mitochondrial proteins, adenine translocase and the beta-subunit of F1-ATPase, was preserved by hypothermia. cDNA arrays revealed that ischemia altered expression of 13 genes. Hypothermia modified this response to ischemia for eight genes, six related to apoptosis. A marked, near fivefold increase in transformation-related protein 53 in I was virtually abrogated in H. Hypothermia also increased expression for the anti-apoptotic Bcl-2 homologue Bcl-x relative to I but decreased expression for the proapoptotic Bcl-2 homologue bak. These data imply that hypothermia modifies signaling pathways for apoptosis and suggest possible mechanisms for hypothermia-induced myocardial protection.     

Distinct effects on heparan sulfate structure by different active site mutations in NDST-1

Heparan sulfate polymerization and modification take place in the Golgi compartment. The modification reactions are initiated by glucosaminyl N-deacetylase/N-sulfotransferase (NDST), a bifunctional enzyme that removes N-acetyl groups from selected N-acetyl-d-glucosamine units followed by N-sulfation of the generated free amino groups. Four isoforms of NDST have been identified. NDST-1 and -2 have a wide and largely overlapping tissue distribution, but it is not known if they can act on the same heparan sulfate chain. We have introduced point mutations into NDST-1 cDNA, which selectively destroy the N-deacetylase or N-sulfotransferase activity of the enzyme [Wei, Z., and Swiedler, S. J. (1999) J. Biol. Chem. 274, 1966-70 and Sueyoshi, T., et al. (1998) FEBS Lett. 433, 211-4]. Stable 293 cell lines expressing the NDST-1 mutants were then generated. Structural analyses of heparan sulfate synthesized by these cells and by cells overexpressing wild-type NDST-1 demonstrate that the N-deacetylation step is not only prerequisite but also rate-limiting, determining the degree of N-sulfation. Transfection of mutant NDST-1 lacking N-deacetylase activity had no effect on heparan sulfate sulfation, while cells expressing wild-type enzyme or NDST-1 lacking N-sulfotransferase activity both resulted in the production of oversulfated heparan sulfate. Since no increase in the amount of N-unsubstituted glucosamine residues was seen after transfection of the mutant lacking N-sulfotransferase activity, the results also suggest that two different enzyme molecules can act on the same glucosamine unit. In addition, we show that oversulfation of heparan sulfate produced by cells tranfected with wild-type NDST-1 or the mutant lacking N-sulfotranferase activity results in decreased sulfation of chondroitin sulfate.