From the Skin to the Brain: Pathophysiology of Colonization and Infection of External Ventricular Drain,a Prospective Observational Study

Ventriculostomy-related infection (VRI) is a serious complication of external ventricular drain (EVD) but its natural history is poorly studied. We prospectively tracked the bacteria pathways from skin towards ventricles to identify the infectious process resulting in ventriculostomy-related colonization (VRC), and VRI. We systematically sampled cerebrospinal fluid (CSF) on a daily basis and collected swabs from both the skin and stopcock every 3.0 days for microbiological analysis including in 101 neurosurgical patient. Risk factors for positive event defined as either VRC or VRI were recorded and related to our microbiological findings. A total of 1261 CSF samples, 473 skin swabs, and 450 stopcock swabs were collected. Skin site was more frequently colonized than stopcock (70 (60%) vs 34 (29%), p = 0.023), and earlier (14 ±1.4 vs 24 ±1.5 days, p<0.0001). Sixty-one (52%) and 32 (27%) skin and stopcock sites were colonized with commensal bacteria, 1 (1%) and 1 (1%) with pathogens, 8 (7%) and 1 (1%) with combined pathogens and commensal bacteria, respectively. Sixteen positive events were diagnosed; a cutaneous origin was identified in 69% of cases. The presence of a pathogen at skin site (6/16 vs 4/85, OR: 11.8, [2.5–56.8], p = 0.002) and CSF leakage (7/16 vs 6/85, OR 10 [2.4–41.2], p = 0.001)) were the two independent significant risk factors statistically linked to positive events occurrence. Our results suggest that VRC and VRI mainly results from an extra-luminal progression of pathogens initially colonizing the skin site where CSF leaks.     

A Bovine Cell Line That Can Be Infected by Natural Sheep Scrapie Prions

Cell culture systems represent a crucial part in basic prion research; yet, cell lines that are susceptible to prions, especially to field isolated prions that were not adapted to rodents, are very rare. The purpose of this study was to identify and characterize a cell line that was susceptible to ruminant-derived prions and to establish a stable prion infection within it. Based on species and tissue of origin as well as PrP expression rate, we pre-selected a total of 33 cell lines that were then challenged with natural and with mouse propagated BSE or scrapie inocula. Here, we report the successful infection of a non-transgenic bovine cell line, a sub-line of the bovine kidney cell line MDBK, with natural sheep scrapie prions. This cell line retained the scrapie infection for more than 200 passages. Selective cloning resulted in cell populations with increased accumulation of PrP^res, although this treatment was not mandatory for retaining the infection. The infection remained stable, even under suboptimal culture conditions. The resulting infectivity of the cells was confirmed by mouse bioassay (Tgbov mice, Tgshp mice). We believe that PES cells used together with other prion permissive cell lines will prove a valuable tool for ongoing efforts to understand and defeat prions and prion diseases.     

Determination of acyclovir by ultrafiltration and high-performance liquid chromatography

A simple, sensitive and rapid high-performance liquid chromatographic (HPLC) procedure to determine total serum acyclovir concentrations is described. The assay involves a heat inactivation step at 56°C to prevent risk of infection, ultrafiltration as a pretreatment step prior to ion-pair reversed-phase liquid chromatography using guanosine as internal standard, and ultraviolet detection at 254 nm. This method has excellent recovery (97–100%), linearity (0.5–100 mg/l) and precision (1.2–8.0% coefficient of variation). The detection limit is 50 μg/l. The assay proved to be suitable for therapeutic drug monitoring of acyclovir.     

A ‘simple clock’ approach of circadian rhythms: An easy way to predict the clock's singularity

A graphical method is presented which allows the prediction of phase resetting curves of circadian rhythms for both type 1 and type 0 resetting, starting from one experimentally determined phase resetting curve. Calculations were based on literature data for the pupal eclosion rhythm of Drosophila pseudoobscura. The method is based on the assumption that for all practical purposes the rhythm may be approached as a “simple clock”, i.e. an oscillator with only one state variable, namely its phase or circadian time, CT. Besides predicting both “types” of phase resetting the method is capable to locate the “position” of the phase singularity and thus the transition from type 1 to type 0 resetting. This graphical method is an elaboration of the “transformation method”, developed in 1972 by A. Johnsson and H. G. Karlsson, which was effective in predicting phase resetting by “strong” stimuli, but failed in the case of “weak” stimuli. Predictions made using the extended transformation method are in good agreement with experimental results obtained with Drosophila. Also for the flesh fly, Sarcophaga argyrostoma, a prediction is made of the position of the phase singularity of the eclosion rhythm and compared with experimental results.     

Interactions between Genetic Variants in AMH and AMHR2 May Modify Age at Natural Menopause

The onset of menopause has important implications on women’s fertility and health. We previously identified genetic variants in genes involved in initial follicle recruitment as potential modifiers of age at natural menopause. The objective of this study was to extend our previous study, by searching for pairwise interactions between tagging single nucleotide polymorphisms (tSNPs) in the 5 genes previously selected (AMH, AMHR2, BMP15, FOXL2, GDF9). We performed a cross-sectional study among 3445 women with a natural menopause participating in the Prospect-EPIC study, a population-based prospective cohort study, initiated between 1993 and 1997. Based on the model-based multifactor dimensionality reduction (MB-MDR) test with a permutation-based maxT correction for multiple testing, we found a statistically significant interaction between rs10407022 in AMH and rs11170547 in AMHR2 (p = 0.019) associated with age at natural menopause. Rs10407022 did not have a statistically significant main effect. However, rs10407022 is an eQTL SNP that has been shown to influence mRNA expression levels in lymphoblastoid cell lines. This study provides additional insights into the genetic background of age at natural menopause and suggests a role of the AMH signaling pathway in the onset of natural menopause. However, these results remain suggestive and replication by independent studies is necessary.     

Die organischen Säuren im Cambialsaft von Larix decidua Mill

Summary The quantitatively most important organic acids in the cambial sap of Larix decidua have been isolated and characterised. Quinic acid predominated and smaller amounts of shikimic acid, malic acid, oxalic acid, amino acids and sugar phosphates were also present. It is shown by the aphid-technique that quinic acid is probably transported in the phloem from the young needles and shoots to the cambial zones of the tree.

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Zweite Mitteilung über den Cambialsaft von Larix decidua. Erste Mitteilung in Planta (Berl.) 73, 155–160 (1967).     

Ventilation distribution in rats: Part 2 -- A comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

ABSTRACT: BACKGROUND: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. METHODS: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. RESULTS: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. CONCLUSION: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.     

Pollination systems in Pogonieae (Orchidaceae: Vanilloideae): A hypothesis of evolution among reward and rewardless flowers

The tribe Pogonieae of Vanilloideae (Orchidaceae) consists of six genera, including Pogoniopsis, a myco-heterotrophic taxon with morphological characteristics distinct from the remaining of the tribe. A hypothesis about the phylogeny of the tribe was inferred, involving all currently recognized genera, based on isolated and combined sequence data of 5.8S, 18S and 26S (nrDNA) regions using parsimony and Bayesian analyses. Phylogenetic analyses show that inclusion of Pogoniopsis turns the tribe Pogonieae paraphyletic. All analyses reveal that Pogoniopsis is closely related to members of Epidendroideae. The pantropical Vanilla is monophyletic if Dictyophyllaria is assumed as synonym of Vanilla. Members of Pogonieae are pollinated by several groups of solitary and social bees, two pollination systems being recognized: reward-producing and deceptive. The molecular phylogeny suggests that ancestrals related to Pogonieae gave rise to two evolutionary lines: a tropical one with reward production of flowers, and a predominantly temperate regions invading line with deceptive flowers. Reward-producing flowers characterize the South and Central American clade (=Cleistes), while deceptive pollination is prominent in the clade that includes North American-Asiatic taxa plus the Amazonian genus Duckeella.