Chiral Biases in Solids by Effect of Shear Gradients: A Speculation on the Deterministic Origin of Biological Homochirality

We present an experimental approach to the study of the chirality of three CM2 meteorite solid samples by direct measurement of the optical activity (circular birefringence; CB). The measurements are based on transmission two modulator generalized ellipsometry in conjuction with microscope optics to map the CB of the samples. In spite of the complexity of such optical analysis, these first results indicate the presence of optically active areas in the meteorite solid matrix. In the case of the Murchison sample the statistics of the CB mapping shows a bimodal distribution with a bias to negative CB values. The composition of the active areas probably corresponds to serpentines and other poorly identified phyllosilicate phases. The results are compatible with the hypothesis that in a mineral-based scenario for the origin of life a CB sign bias in the chiral fractures originated by mechanical and flow shear gradients on clays could be later transferred to the reactions of the absorbed organic compounds.     

Reaction of cyanamide and their derivatives with (η-C5H5)Mn(CO)3 and (η-C5H4CH3)Mn(CO)3

The reaction of cyanamide and its derivatives with the (η⁵-C₅H₅)Mn(CO)₂(THF) and (η⁵-C₅H₄CH₃)Mn(CO)₂(THF) complexes affords the cyanamide substituted complexes of types (η⁵-C₅H₅)Mn(CO)₂(NCN(R′)(R″)) (2a-d) and (η⁵-C₅H₄CH₃)Mn(CO)₂(NCN(R′)(R″)) (3a-e). All complexes were characterized by spectroscopy (¹H, ¹³C NMR, IR), elemental and mass spectroscopy analysis. Complex 2b (η⁵-C₅H₅)Mn(CO)₂(NCN(CH₃)₂) was additionally examined by single crystal X-ray structure determination.     

Knowledge and Attitudes of GPs in Saxony-Anhalt concerning the Psychological Aspects of Bronchial Asthma: A Questionnaire Study

Bronchial Asthma is a worldwide condition with particularly high prevalence in first world countries. The reasons are multifactorial but a neglected area is the psychological domain. It is well known that heavy emotions can trigger attacks and that depression negatively affects treatment outcomes. It is also known that personality type has a greater effect on disease prevalence than in many other conditions. However, many potential psychological treatments are hardly considered, neither in treatment guidelines nor in reviews by asthma specialists. Moreover, there is very little research concerning the beliefs and practices of doctors regarding psychological treatments. Using a questionnaire survey we ascertained that local GPs in Saxony-Anhalt have reasonably good knowledge about the psychological elements of asthma; a third consider it to be some of the influence (20-40% aetiology) and a further third consider it to be even more important than that (at least 40% total aetiology). Our GPs use psychosomatic counseling sometimes or usually in the areas of sport and smoking (circa 85% GPs), although less so regarding breathing techniques and relaxation (c40% usually or sometimes do this) However despite this knowledge they refer to the relevant clinicians very rarely (98% sometimes, usually or always refer to a respiratory physician compared with only 11% referring for psychological help).     

Oblique Bile Duct Predisposes to the Recurrence of Bile Duct Stones

Background and Study Aims

Bile stones represent a highly prevalent condition and abnormalities of the biliary tree predispose to stone recurrence due to development of biliary stasis. In our study, we assessed the importance of an altered bile duct course for stone formation.

Patients and Methods

1,307 patients with choledocholithiasis in the absence of any associated hepatobiliary disease who underwent endoscopic retrograde cholangiopancreatography (ERCP) between 2002 and 2009 were analysed. The angle enclosed between the horizontal portion of the common bile duct (CBD) and the horizontal plane was measured (angle α). Oblique common bile duct (OCBD) was defined as a CBD with angle α<45°.

Results

103 patients (7.9%) were found to harbour OCBD and these were compared to 104 randomly selected control subjects. Compared to controls, OCBD patients were (i) significantly older (72±13 vs. 67±13, p<0.00001); (ii) more frequently underwent a cholecystectomy (p = 0.02) and biliary surgery (p = 0.003) prior to the diagnosis and (iii) more often developed chronic pancreatitis (p = 0.04) as well as biliary fistulae (p = 0.03). Prior to and after ERCP, OCBD subjects displayed significantly elevated cholestatic parameters and angle α negatively correlated with common bile duct diameter (r = -0.29, p = 0.003). OCBD subjects more often required multiple back-to-back ERCP sessions to remove bile stones (p = 0.005) as well as more ERCPs later on due to recurrent stone formation (p<0.05).

Conclusion

OCBD defines a novel variant of the biliary tree, which is associated with chronic cholestasis, hampers an efficient stone removal and predisposes to recurrence of bile duct stones.     

Induction of Premalignant Host Responses by Cathepsin X/Z-Deficiency in Helicobacter Pylori-Infected Mice

Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz^−/−positive macrophages and the up-regulation of Ctsz in tumor epithelium. To explore the Ctsz-function in the context of chronic inflammation and the development of preneoplastic lesions, we used Ctsz-deficient mice in a H. pylori gastritis model. Ctsz ^−/− and wild-type (wt) mice were infected with H. pylori strain SS1. The mice were sacrificed at 24, 36, and 50 weeks post infection (wpi). The stomach was removed, and gastric strips were snap-frozen or embedded and stained with H&E. Tissue sections were scored for epithelial lesions and inflammation. Ki-67 and F4/80 immunostaining were used to measure epithelial cell proliferation and macrophage infiltration, respectively. The upregulation of compensating cathepsins and cytokines were confirmed by Western blotting and quantitative RT-PCR. SS1-infected wt and ctsz ^−/− mice showed strong inflammation, foveolar hyperplasia, atrophy, and cystically-dilated glands. However, at 50 wpi, ctsz ^−/− mice developed significantly more severe spasmolytic polypeptide-expressing metaplasia (SPEM), showed enhanced epithelial proliferation, and higher levels of infiltrating macrophages. Induction of cytokines was higher and significantly prolonged in ctsz ^−/− mice compared to wt. Ctsz deficiency supports H. pylori-dependent development of chronic gastritis up to metaplasia, indicating a protective, but not proteolytic, function of Ctsz in inflammatory gastric disease.     

Koninklijk Zoölogisch-Botanisch Genootschap,the Zoological Garden in The Hague, 1863-1943, a Retrospect after Seventy Years from the Point of View of a Zoologist

The zoological garden in The Hague, the de facto capital of the Netherlands, founded in 1863, was forced to close during the Second World War in 1943 by order of the German occupation forces. An attempt to reconstruct its history from the point of view of a zoologist shows that in eighty years about 180 species of mammals were kept; the garden acquired a certain fame because of its primate collection, e.g., having early success with Sumatran Orang-utan (Pongo abelii), and the discovery of the Black Mangabey (Cercocebus aterrimus) in 1890. Many unusual, nowadays rare, species [e.g., Ursine Tree Kangaroo (Dendrolagus ursinus), Sumatran Bamboo Rat (Rhizomys sumatranus), Marbled Cat (Pardofelis marmorata), Malay Tapir (Tapirus indicus)] were present at times, occasionally also on deposit from animal dealers. The majority of the animals originated from the Netherlands East Indies (now Indonesia) and were donated by colonial residents, such as Sumatran Elephant (Elephas maximus sumatranus) and Orang-utan. The colony of Surinam in South America was another supplier of zoo animals and until the 1880s animals were also derived from a few Dutch trading posts in West Africa. The bird collections were always rich and varied, initially specializing in local species. Later this collection became more comprehensive; attention is drawn to early success with birds of paradise and the presence of now extinct species such as the Carolina Parakeet (Conuropsis carolinensis) and the Passenger Pigeon (Ectopistes migratorius). Series of lower vertebrates [among them the Japanese Giant Salamander (Andrias japonicus)] and invertebrates were always on display in a modest aquarium. At the turn of the century the Netherlands only harboured three zoological gardens (Amsterdam – 1838; Rotterdam – 1857; The Hague – 1863). The one in The Hague, although subject to an almost permanent financial crisis, nevertheless succeeded in playing a modest role in this field of zoological science.     

Computational polymer dynamics via DL_POLY

A review is presented of recent work in the group utilising the DL_POLY molecular dynamics package. Simulations have been performed across several areas of polymer physics including the dynamics of polyethylene as a function of density and chain length, the rheology of trifunctional dendrimers, and penetrant diffusion with a macromolecular matrix. The methodology and conclusions of these investigations are reviewed.     

Dobutamine in Paediatric Population: A Systematic Review in Juvenile Animal Models

Objective

Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/paediatric population.

Methods

Studies were identified by searching MEDLINE (1946–2012) and EMBASE (1974–2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included.

Results

Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions.

Conclusion

There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.     

In Vitro Surfactant and Perfluorocarbon Aerosol Deposition in a Neonatal Physical Model of the Upper Conducting Airways

Objective

Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways.

Methods

The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4–7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted.

Results

The nebulization system produced relatively large amounts of aerosol ranging between 0.3±0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0±0.1 ml/min for distilled water (H₂Od) at 6 bar, with MMADs between 2.61±0.1 µm for PFD at 7 bar and 10.18±0.4 µm for FC-75 at 6 bar. The deposition study showed that for surfactant and H₂Od aerosols, the highest percentage of the aerosolized mass (∼65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH₂O only increased total airway pressure by 1.59 cmH₂O at the highest driving pressure (7 bar).

Conclusion

This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.