HLE-inhibitory alkaloids with a polyketide skeleton from the marine-derived fungus Coniothyrium cereale

The marine endophytic fungus Coniothyrium cereale produces the structurally unusual polyketide-type alkaloids (-)-cereolactam (1) and (-)-cereoaldomine (3), incorporating a lactam and an imine functionality, respectively, as well as the related metabolite (-)-trypethelone (2). Compounds 1 and 3 showed selective inhibition of human leukocyte elastase with IC50 values of 9.28 and 3.01 μM, respectively. Compound 2 was found to be inhibitory toward Mycobacterium phlei, Staphylococcus aureus, and Escherichia coli and also cytotoxic against mouse fibroblast cells (IC50=7.5 μM).     

Another novel subgenotype of hepatitis B virus genotype C from papuans of Highland origin

Hepatitis B virus (HBV) genotypes and subtypes have been identified worldwide. As HBV genotypes/subtypes, the HBV subgenotypes seem to be associated with their geographical distribution and ethnic origin. A previous study showed the novel HBV subgenotype C6 based on the complete genome sequences of isolates in Papua, Indonesia. In the present study, further characterization of HBV in Jayapura (capital of Papua Province), particularly from native people of Papua originating from the highland (highland Papuans) and those from the lowland (lowland Papuans) were examined. Of 32 HBV isolates from both highland and lowland Papuan blood donors with HBsAg positive, part of the S gene and the core gene sequences were analyzed. Analyses of some isolates from highland Papuans were confirmed by the complete genome sequences. Most HBV isolates were classified into genotype C (78.1%), followed by genotype B (18.8%), and genotype D (3.1%). The subtype adr was predominant (71.9%), followed by adw2 (25.1%), and ayw2 (3.1%). As with previous findings, phylogenetic analyses revealed that most HBV isolates from Papuans, C/adr, belonged to subgenotype C6. Interestingly, some C/adr isolates from highland Papuans formed a distinct cluster from all reported subgenotypes of HBV/C, and they differed from HBV/C1-C10 by 4.2-7.2% over the complete genome. SimPlot analysis showed no evidence of recombination with HBV/C1-C10. The isolated life and closed social systems of highland Papuans, even though some have been moving to Jayapura, likely contribute to the formation of this unique cluster of infection with a novel subgenotype of HBV, named C11.     

Weaning difficult-to-wean chronic obstructive pulmonary disease patients: A pilot study comparing initial hemodynamic effects of levosimendan and dobutamine

Purpose

To compare the short-term hemodynamic effects of levosimendan and dobutamine in chronic obstructive pulmonary disease (COPD) patients experiencing weaning difficulties in relation with increased left ventricular filling pressure.

Materials and Methods

This prospective, sequential, pilot study included 10 COPD patients experiencing weaning difficulties in relation with increased left ventricular filling pressure ascertained by an increase >10 mm Hg of pulmonary artery occlusion pressure (PAOP) at the shift from mechanical to spontaneous breathing (SB). Patients received 1 h infusion of 7 μg/kg per minute of dobutamine, followed by 24-hour infusion of 0.2 μg/kg per minute levosimendan. Hemodynamic variables were measured under MV and 15 to 30 minutes after SB at baseline, at the end of dobutamine infusion, at a washout period, and after levosimendan infusion.

Results

At baseline, the shift from mechanical ventilation to spontaneous ventilation was associated with a significant increase in PAOP from a median of 15 (interquartile range [IQR], 6) to 29 (9) mm Hg. Both drugs reduced significantly the level of PAOP increase at SB, but levosimendan had a greater effect than dobutamine [median PAOP increase (IQR): 5 (2) vs 9 (4) mm Hg, respectively; P < .01].

Conclusions

Both drugs reduced the magnitude of PAOP increase at SB in difficult-to-wean COPD patients. PAOP increase was reduced to a greater extent by levosimendan.     

An updated study-level meta-analysis of randomised controlled trials on proning in ARDS and acute lung injury

Introduction  

In patients with acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), recent randomised controlled trials (RCTs) showed a consistent trend of mortality reduction with prone ventilation. We updated a meta-analysis on this topic.     

3D movement correction of CT brain perfusion image data of patients with acute ischemic stroke

Introduction

Head movement during CT brain perfusion (CTP) acquisition can deteriorate the accuracy of CTP analysis. Most CTP software packages can only correct in-plane movement and are limited to small ranges. The purpose of this study is to validate a novel 3D correction method for head movement during CTP acquisition.

Methods

Thirty-five CTP datasets that were classified as defective due to head movement were included in this study. All CTP time frames were registered with non-contrast CT data using a 3D rigid registration method. Location and appearance of ischemic area in summary maps derived from original and registered CTP datasets were qualitative compared with follow-up non-contrast CT. A quality score (QS) of 0 to 3 was used to express the degree of agreement. Furthermore, experts compared the quality of both summary maps and assigned the improvement score (IS) of the CTP analysis, ranging from ?2 (much worse) to 2 (much better).

Results

Summary maps generated from corrected CTP significantly agreed better with appearance of infarct on follow-up CT with mean QS 2.3 versus mean QS 1.8 for summary maps from original CTP (P?=?0.024). In comparison to original CTP data, correction resulted in a quality improvement with average IS 0.8: 17 % worsened (IS?=??2, ?1), 20 % remained unchanged (IS?=?0), and 63 % improved (IS?=?+1, +2).

Conclusion

The proposed 3D movement correction improves the summary map quality for CTP datasets with severe head movement.     

Head movement during CT brain perfusion acquisition of patients with suspected acute ischemic stroke

Objective

Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition.

Methods

From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t-test respectively.

Results

Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1 mm and 22.6 mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics.

Conclusions

Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement.