Consensus Statement on High-Intensity Focused Ultrasound for Functional Neurosurgery in Switzerland.

Background: Magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) has evolved into a viable ablative treatment option for functional neurosurgery. However, it is not clear yet, how this new technology should be integrated into current and established clinical practice and a consensus should be found about recommended indications, stereotactic targets, patient selection, and outcome measurements. Objective: To sum up and unify current knowledge and clinical experience of Swiss neurological and neurosurgical communities regarding MRgHiFUS interventions for brain disorders to be published as a national consensus paper. Methods: Eighteen experienced neurosurgeons and neurologists practicing in Switzerland in the field of movement disorders and one health physicist representing 15 departments of 12 Swiss clinical centers and 5 medical societies participated in the workshop and contributed to the consensus paper. All experts have experience with current treatment modalities or with MRgHiFUS. They were invited to participate in two workshops and consensus meetings and one online meeting. As part of workshop preparations, a thorough literature review was undertaken and distributed among participants together with a list of relevant discussion topics. Special emphasis was put on current experience and practice, and areas of controversy regarding clinical application of MRgHiFUS for functional neurosurgery. Results: The recommendations addressed lesioning for treatment of brain disorders in general, and with respect to MRgHiFUS indications, stereotactic targets, treatment alternatives, patient selection and management, standardization of reporting and follow-up, and initialization of a national registry for interventional therapies of movement disorders. Good clinical evidence is presently only available for unilateral thalamic lesioning in treating essential tremor or tremor-dominant Parkinson's disease and, to a minor extent, for unilateral subthalamotomy for Parkinson's disease motor features. However, the workgroup unequivocally recommends further exploration and adaptation of MRgHiFUS-based functional lesioning interventions and confirms the need for outcome-based evaluation of these approaches based on a unified registry. MRgHiFUS and DBS should be evaluated by experts familiar with both methods, as they are mutually complementing therapy options to be appreciated for their distinct advantages and potential. Conclusion: This multidisciplinary consensus paper is a representative current recommendation for safe implementation and standardized practice of MRgHiFUS treatments for functional neurosurgery in Switzerland.

The surname structure of Trentino (Italy) and its relationship with dialects and genes.

BACKGROUND: Thanks to the availability of rich surname, linguistic and genetic information, together with its geographic and cultural complexity, Trentino (North-Eastern Italy) is an ideal place to test the relationships between genetic and cultural traits. AIM: We provide a comprehensive study of population structures based on surname and dialect variability and evaluate their relationships with genetic diversity in Trentino. SUBJECTS AND METHODS: Surname data were collected for 363 parishes, linguistic data for 57 dialects and genetic data for different sets of molecular markers (Y-chromosome, mtDNA, autosomal) in 10 populations. Analyses relied on different multivariate methods and correlation tests. RESULTS: Besides the expected isolation-by-distance-like patterns (with few local exceptions, likely related to sociocultural instances), we detected a significant and geography-independent association between dialects and surnames. As for molecular markers, only Y-chromosomal STRs seem to be associated with the dialects, although no significant result was obtained. No evidence for correlation between molecular markers and surnames was observed. CONCLUSION: Surnames act as cultural markers as do other words, although in this context they cannot be used as reliable proxies for genetic variability at a local scale.

One-pot preparation of dendrimer-gold nanoparticle hybrids in a dipolar aprotic solvent.

We present a simple one-pot, one-step method to obtain stable and nearly monodisperse gold nanoparticles in dipolar aprotic solvents. Novel thiomethyl-functionalized polyphenylene dendrimers are used to control the growth and stabilize the nanoparticles in suspension. The dendrimer functionalized gold nanoparticles have an average size of roughly 10 nm and are stable in suspension for several weeks. The stability in dipolar aprotic solvents and the great functionalization flexibility offered by the dendrimers make these metal/dendrimer hybrid systems promising for applications such as nanophotonics, molecular electronics, and sensing.

Guiding the self-assembly of a second-generation polyphenylene dendrimer into well-defined patterns.

A second-generation polyphenylene dendrimer 1 is shown to self-assemble into nanofibers. To guide the formation of the dendrimer fibers into well-defined patterns, 1H,1H,2H,2H-perfluorodecyltrichlorosilane is grafted in the gas phase onto a silicon substrate. De-wetting of the solution on the nanopatterned surface results in the formation of a nanostructured template, into which fiber growth subsequently occurs under the constraints set by the de-wetted morphology.

Interferon-beta 1b leads to a short-term increase of soluble but long-term stabilisation of cell surface bound adhesion molecules in multiple sclerosis.

Adhesion molecules (AMs) are believed to regulate the transmigration of blood leukocytes across the blood-brain barrier (BBB), which is an essential step in the pathogenesis of multiple sclerosis (MS). Previous studies have investigated changes of the soluble forms of AM during interferon-beta1b (IFN-beta1b) treatment in MS patients. In this study, we analysed the influence of IFN-beta1b treatment on the cell surface bound forms of the AMs cICAM-1 and cICAM-3 on blood mononuclear cells (MNC). Sixty-eight patients with relapsing-remitting MS were enrolled in this open study; thirty of them were treated with IFN-beta1b. Blood samples were collected every three months over a period of 18 months. The expression levels of cell surface bound forms of AM on blood MNC were measured by two colour flow cytometry analysis. sVCAM-1, sICAM-1 and sICAM-3 were determined by ELISA. We found a short-term induction effect on the serum concentrations of sICAM-1 and sVCAM-1 after three months of IFN-beta1b treatment. The expression levels of cell surface bound AMs on blood MNC remained stable during treatment. Untreated MS patients, however, showed a continuous decrease in the expression of cell surface bound AM expression over 18 months. Stabilisation of the expression of cell surface bound AMs on blood MNC may indicate the beneficial effects of IFN-beta1b therapy in MS patients.

Nanosized molecular propellers by cyclodehydrogenation of polyphenylene dendrimers.

In a polymer analogous approach, large dendritic oligophenylenes containing benzene and tetraphenylmethane cores are transformed via oxidative cyclodehydrogenation to novel propeller-shaped molecules with large polycyclic aromatic hydrocarbon units as "blades". Structure analysis is performed by a combination of MALDI-TOF mass spectrometry, UV/vis, fluorescence, and Raman spectroscopy using solid-state sample preparation methods. These methods are also utilized to determine the degree of the cyclodehydrogenation reaction.

Development of an in vitro blood-brain barrier model based on immortalized porcine brain microvascular endothelial cells.

Immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) were used to develop a model for measurement of blood-brain barrier permeation of central nervous system active drugs. Previous studies showed that a system using C6 astrocyte glioma conditioned medium leads to cell layers with transendothelial electrical resistance values up to 300 Omega cm(2) and a permeability coefficient P(e) of 3.24 +/- 0.14 x 10(-4) cm/min for U-[(14)C]sucrose, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro. However, commercially available inserts for the Transwell system were not permeable for highly lipophilic compounds, such as diazepam. Systematic studies with different insert showed, that inserts with a pore width of 1 microm proved to be optimal for permeation studies of lipophilic compounds. Permeability studies with a set of three benzodiazepines further supported this finding.

Single-crystal structures of polyphenylene dendrimers.

A series of first-generation polyphenylene dendrimers based on three different cores were prepared by Diels-Alder cycloaddition and their single-crystal structures were determined. Consisting exclusively of interlocked, twisted phenyl rings, these polyphenylene nanostructures have exciting structural and dynamic properties. Single crystals of dendrimers, suitable for X-ray structure analysis, were grown from different solvent mixtures by slow evaporation at room temperature. It should be pointed out that one of the described polyphenylene dendrimers represents up to now the biggest oligophenylene nanostructure from which crystallographic data is available.