Creutzfeldt-Jakob disease and homocysteine levels in plasma and cerebrospinal fluid

Background: There is evidence that homocysteine contributes to various neurodegenerative disorders. Objective: To assess the values of homocysteine in patients with Creutzfeldt-Jakob disease (CJD) in both cerebrospinal fluid (CSF) and plasma. Methods: Study design: Case control study. Total homocysteine was quantified in CSF and plasma samples of CJD patients (n = 13) and healthy controls (n = 13). Results: Mean values in healthy controls: 0.15 mumol/l +/- 0.07 (CSF) and 9.10 mumol/l +/- 2.99 (plasma); mean values in CJD patients: 0.13 mumol/l +/- 0.03 (CSF) and 9.22 mumol/l +/- 1.81 (plasma). No significant differences between CJD patients and controls were observed (Mann-Whitney U, p > 0.05). Conclusions: The results indicate that the CSF and plasma of CJD patients showed no higher endogenous levels of homocysteine as compared to normal healthy controls. These findings provide no evidence for an additional role of homocysteine in the pathogenetic mechanisms underlying CJD neurodegeneration. Copyright (C) 2005 S. Karger AG, Basel

Country differences in the diagnosis and management of coronary heart disease : a comparison between the US, the UK and Germany

Background The way patients with coronary heart disease (CHD) are treated is partly determined by non-medical factors. There is a solid body of evidence that patient and physician characteristics influence doctors' management decisions. Relatively little is known about the role of structural issues in the decision making process. This study focuses on the question whether doctors' diagnostic and therapeutic decisions are influenced by the health care system in which they take place. This non-medical determinant of medical decision-making was investigated in an international research project in the US, the UK and Germany. Methods Videotaped patients within an experimental study design were used. Experienced actors played the role of patients with symptoms of CHD. Several alternative versions were taped featuring the same script with patients of different sex, age and social status. The videotapes were shown to 384 randomly selected primary care physicians in the three countries under study. The sample was stratified on gender and duration of professional experience. Physicians were asked how they would diagnose and manage the patient after watching the video vignette using a questionnaire with standardised and open-ended questions. Results Results show only small differences in decision making between British and American physicians in essential aspects of care. About 90% of the UK and US doctors identified CHD as one of the possible diagnoses. Further similarities were found in test ordering and lifestyle advice. Some differences between the US and UK were found in the certainty of the diagnoses, prescribed medications and referral behaviour. There are numerous significant differences between Germany and the other two countries. German physicians would ask fewer questions, they would order fewer tests, prescribe fewer medications and give less lifestyle advice. Conclusion Although all physicians in the three countries under study were presented exactly the same patient, some disparities in the diagnostic and patient management decisions were evident. Since other possible influences on doctors treatment decisions are controlled within the experimental design, characteristics of the health care system seem to be a crucial factor within the decision making process

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

A demonstration of 'broken' visual space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A > B > D yet also A < C < D) and hence no single one-to-one mapping between participants’ perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants’ performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent 3D internal representation of a scene

Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B

Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites

A Rydberg Quantum Simulator

Following Feynman and as elaborated on by Lloyd, a universal quantum simulator (QS) is a controlled quantum device which reproduces the dynamics of any other many particle quantum system with short range interactions. This dynamics can refer to both coherent Hamiltonian and dissipative open system evolution. We investigate how laser excited Rydberg atoms in large spacing optical or magnetic lattices can provide an efficient implementation of a universal QS for spin models involving (high order) n-body interactions. This includes the simulation of Hamiltonians of exotic spin models involving n-particle constraints such as the Kitaev toric code, color code, and lattice gauge theories with spin liquid phases. In addition, it provides the ingredients for dissipative preparation of entangled states based on engineering n-particle reservoir couplings. The key basic building blocks of our architecture are efficient and high-fidelity n-qubit entangling gates via auxiliary Rydberg atoms, including a possible dissipative time step via optical pumping. This allows to mimic the time evolution of the system by a sequence of fast, parallel and high-fidelity n-particle coherent and dissipative Rydberg gates.Comment: 8 pages, 4 figure

Trauma induces apoptosis in human thoracolumbar intervertebral discs

BACKGROUND: Vertebral fractures resulting from high energy trauma often comprise the risk of posttraumatic degenerative changes in the affected intervertebral discs (IVD). Particularly in conservatively treated patients, or in cases after implant removal of an exclusively posterior stabilization, consecutive disc degeneration and the associated functional losing of the spinal segment clearly represent detrimental treatment results. In this regard, apoptosis of IVD cells has been suggested to be involved in the critical changes of the extracellular matrix. METHODS: To investigate whether fractures of the vertebrae induce apoptosis in the affected IVD, disc tissue from patients (n = 17) undergoing open reduction and internal fixation of thoracolumbar spine fractures were analysed in regards to caspase activity, apoptosis-receptor expression levels and gene expression of apoptosis-regulating proteins such as Bax and Bcl-2. Healthy IVD tissue (n = 3) obtained from patients undergoing surgical resection of adjacent vertebrae were used as control samples. RESULTS: In contrast to healthy control IVD tissues, samples from traumatic thoracolumbar IVD showed positive TUNEL staining and a significant increase of caspase-3/7 activity. Interestingly, analyses of the initiator caspase-8 and -9 revealed significantly increased activation levels compared to control values, suggesting the coexistent activation of both the extrinsic (receptor-mediated) and intrinsic (mitochondria-mediated) apoptosis pathway. Accordingly, expression levels of the Fas receptor (FasR) mRNA were significantly increased. Although the TNF receptor I (TNFR I) was only slightly upregulated, corresponding TNFα from trauma IVD presented significantly increased mRNA expression values. Furthermore, traumatic IVD cells demonstrated significantly reduced expression of the mitochondria-bound anti-apoptotic Bcl-2, thereby maintaining baseline transcriptional levels of the pro-apoptotic Bax protein when compared to control IVD cells. CONCLUSION: Our data suggest that thoracolumbar fractures induce early caspase-dependent apoptosis in IVD cells of the affected intervertebral disc, in part, by downregulation of the anti-apoptotic protein Bcl-2 (intrinsic apoptosis pathway), as well as signalling via the death receptor complex (TNFR I and FasR)

The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

Treatment of distal humeral fractures using conventional implants. Biomechanical evaluation of a new implant configuration

<p>Abstract</p> <p>Background</p> <p>In the face of costly fixation hardware with varying performance for treatment of distal humeral fractures, a novel technique (U-Frame) is proposed using conventional implants in a 180° plate arrangement. In this in-vitro study the biomechanical stability of this method was compared with the established technique which utilizes angular stable locking compression plates (LCP) in a 90° configuration.</p> <p>Methods</p> <p>An unstable distal 3-part fracture (AO 13-C2.3) was created in eight pairs of human cadaveric humeri. All bone pairs were operated with either the "Frame" technique, where two parallel plates are distally interconnected, or with the LCP technique. The specimens were cyclically loaded in simulated flexion and extension of the arm until failure of the construct occurred. Motion of all fragments was tracked by means of optical motion capturing. Construct stiffness and cycles to failure were identified for all specimens.</p> <p>Results</p> <p>Compared to the LCP constructs, the "Frame" technique revealed significant higher construct stiffness in extension of the arm (P = 0.01). The stiffness in flexion was not significantly different (P = 0.16). Number of cycles to failure was found significantly larger for the "Frame" technique (P = 0.01).</p> <p>Conclusions</p> <p>In an in-vitro context the proposed method offers enhanced biomechanical stability and at the same time significantly reduces implant costs.</p

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles