External Validation of the Derived Neutrophil to Lymphocyte Ratio as a Prognostic Marker on a Large Cohort of Pancreatic Cancer Patients

Background

With growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients.

Methods

Data from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.

Results

We calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients’ survival in the whole cohort. Kaplan-Meier curve reveals a dNLR≥2.3 as a factor for decreased CSS in PC patients (p<0.001, log-rank test). An independent significant association between high dNLR≥2.3 and poor clinical outcome in multivariate analysis (HR = 1.24, CI95% = 1.01–1.51, p = 0.041) was identified.

Conclusion

In the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability.     

Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls

Background

Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD).

Methodology/Principal Findings

MBF was measured with ¹⁵O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58±13 years) and in CAD patients (n = 15, mean age 61±9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26±0.56 vs. 2.02±0.56, P<0.005), remote (2.40±0.70 vs. 1.78±0.46, P<0.001) and in stenotic segments (1.90±0.41 vs. 1.38±0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline).

Conclusions

We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls.     

Multimerization of Drosophila sperm protein Mst77F causes a unique condensed chromatin structure

Despite insights on the cellular level, the molecular details of chromatin reorganization in sperm development, which involves replacement of histone proteins by specialized factors to allow ultra most condensation of the genome, are not well understood. Protamines are dispensable for DNA condensation during Drosophila post-meiotic spermatogenesis. Therefore, we analyzed the interaction of Mst77F, another very basic testis-specific protein with chromatin and DNA as well as studied the molecular consequences of such binding. We show that Mst77F on its own causes severe chromatin and DNA aggregation. An intrinsically unstructured domain in the C-terminus of Mst77F binds DNA via electrostatic interaction. This binding results in structural reorganization of the domain, which induces interaction with an N-terminal region of the protein. Via putative cooperative effects Mst77F is induced to multimerize in this state causing DNA aggregation. In agreement, overexpression of Mst77F results in chromatin aggregation in fly sperm. Based on these findings we postulate that Mst77F is crucial for sperm development by giving rise to a unique condensed chromatin structure.     

Sperm lengths of non‐marine cypridoidean ostracods (Crustacea)

Length measurements of sperms of 51 species of Cypridoidea ostracods were taken to supplement the paucity of ostracod sperm data in the published literature. The lengths of the posterior regions (carrying the mitochondria) and the thinner anterior regions were also measured when appropriate. Maximum lengths of sperms for individual species varied from 268 μm for Fabaeformiscandona velifera Smith and Janz, 2008 through to 11 787 μm for Australocypris robusta De Deckker, 1974; these lengths represent the shortest so far recorded for the superfamily and the longest ever recorded in ostracods, respectively. There appears to be only a loose relationship between taxonomy and sperm lengths. Species of the subfamily Candoninae generally have the shortest sperms compared with other subfamilies, but one Candoninae species, Candona altoides Petkovski, 1961, has sperms longer than some species of the families Cyprididae, Ilyocyprididae and Notodromadidae. The family Cyprididae showed the most variation, with sperms ranging from 1000 μm through to 11 787 μm in length. No hypothesis satisfactorily explains the origin of giant sperms in ostracods or the longevity of this trait through geological eras, and their existence remains enigmatic.     

Inhibition of Swarming of Proteus by Sodium Tetradecyl Sulfate, β-Phenethyl Alcohol,and p-Nitrophenylglycerine

The effects of sodium tetradecyl sulfate (STS), β-phenethyl alcohol (PEA), and p-nitrophenylglycerol (PNPG) on motility, swarming, flagellation, and growth of Proteus were examined. Growth-inhibitory concentrations (GIC) and swarming-inhibitory concentrations (SIC) were determined. A characterization of the swarming-inhibitory efficacy of these compounds was based on their GIC/SIC ratio and their concentration inhibition curves. Using the homologous series of sodium alkyl sulfates as a standard reference, we showed that PNPG was more effective than STS, which was the most effective of the homologous series. PEA was less effective than sodium decyl sulfate but more effective than sodium octyl sulfate. Motility tests in liquid medium and electron microscope investigations indicated that the modes of action of the three compounds, all of which effectively inhibit the swarming of Proteus, are different. Whereas STS and PEA inhibit swarming by inhibition of motility, PNPG seems to act on the swarming mechanism sensu strictori, without impairment of motility. STS immobilizes by inhibition of flagellum formation or by some lytic action on the flagella already synthesized. PEA acts by impairing flagellar function, but leaves the flagella morphologically intact.     

Histochemical evidence for lysosomal storage of acid glycosaminoglycans in splenic cells of rats treated with tilorone

Summary Tilorone, an agent with antiviral and antitumor activities, has previously been reported to produce clear cytoplasmic vacuoles in many cell types of the rat. The present study on rat spleen was planned to investigate the ultrastructural and histochemical features of the tilorone-induced vacuoles occurring in sinus endothelium, trabecular smooth muscle cells, and macrophages of the red pulp. Evidence was obtained that the vacuoles represent lysosomes overloaded with acid glycosaminoglycans (aGAG). The main purpose of the present study was to overcome the technical difficulties of preserving the intralysosomal storage materials which were highly water-soluble and non-fixable by aldehyde fixatives. Preservation, at least for the light microscopical level, was achieved by freeze drying and by means of cationic dyes which served also to characterize the storage materials on the basis of their acidities. Tissue slices were used to determine the critical MgCl₂ concentration necessary to abolish Alcian blue staining; cartilage and mast cells served as references. For the storage material in sinus endothelium, the critical MgCl₂ concentration was found to be >0.7 M, as compared to >0.5 M for cartilage and >0.9 M for mast cells. The storage materials in trabecular cells and macrophages were slightly less acidic than cartilagineous matrix and more heterogeneous than that in sinus endothelium. Ultrastructurally, positive staining with high iron diamine (HID) confirmed the presence of aGAG within the tilorone-induced vacuoles.     

How is a giant sperm ejaculator formed? Development of the Zenker organ after the last moult in Pseudocandona marchica (Crustacea,Ostracoda, Candonidae)

‘Giant sperm’, in terms of exceptionally long spermatozoa, occur in various taxa in the animal kingdom, particularly in arthropods. In freshwater ostracods (Cypridoidea) reproducing with giant sperm, males are equipped with a pair of specialized ejaculators, or Zenker organs, located in the distal part of vas deferens.