Identification of Brain-Penetrant ATP-Competitive mTOR Inhibitors for CNS Syndromes.

The allosteric inhibitor of the mechanistic target of rapamycin (mTOR) everolimus reduces seizures in tuberous sclerosis complex (TSC) patients through partial inhibition of mTOR functions. Due to its limited brain permeability, we sought to develop a catalytic mTOR inhibitor optimized for central nervous system (CNS) indications. We recently reported an mTOR inhibitor () that is able to block mTOR functions in the mouse brain and extend the survival of mice with neuronal-specific ablation of the 1 gene.

[SICOVID: a cantonal COVID information system for public health decision-making].

Late 2019 a new coronavirus appeared, creating a pandemic, with the first case in Switzerland detected on the 25th of February 2020. Considering the rapid increase in the number of cases, with the fear of an over-burdening of the sanitary network, the Canton of Vaud created a surveillance system (SICOVID). The objective of the SICOVID was to produce a set of indicators, covering the breadth of the epidemiological impact and response as the epidemic progressed.

Switching costs in competitive health insurance markets: The role of insurers' pricing strategies.

Our article deals with pricing strategies in Swiss health insurance markets and focuses on the relationship between basic and supplementary insurance. We analyzed how firms' pricing strategies (i.e.

Systemic Inflammation in Pregnant Women With Periodontitis and Preterm Prelabor Rupture of Membranes: A Prospective Case-Control Study.

Periodontal disease is associated with adverse pregnancy outcome, but the underlying pathophysiologic mechanism is still unknown. In this prospective, longitudinal, non-interventional case-control study, 45 women with preterm premature rupture of membranes and 26 controls with uncomplicated pregnancies were examined at three time-points (T1: 20-34 weeks of gestations; T2: within 48 h after delivery; T3: 4-6 weeks post partum). Examinations included subgingival, blood, vaginal, and placenta sampling for microbiologic, cytokine, and histology assessment.

Heterogeneity in The drivers of health expenditures financed by health insurance in a fragmented health system: The case of Switzerland.

Switzerland is the world's second largest spender on health care, both per capita and as a share of the Gross Domestic Product (GDP). The Swiss health care system is a federation of 26 cantonal systems with highly fragmented provision and financing of care, leading to important geographical disparities in expenditures. We propose a simple conceptual framework to guide the decomposition of health care expenditures into five core components (i.

Micronucleus Analysis by Flow Cytometry.

During the last two decades the micronucleus (MN) test has been extensively used as a genotoxicity screening tool of chemicals and in a variety of exploratory and mechanistic investigations. The MN is a biomarker for chromosomal damage or mitotic abnormalities since it can originate from chromosome fragments or whole chromosomes that fail to be incorporated into daughter nuclei during mitosis (Fenech et al., Mutagenesis 26: 125-132, 2011; Kirsch-Volders et al.

Exploring differences in healthcare utilization of prisoners in the Canton of Vaud, Switzerland.

Prison healthcare is an important public health concern given the increasing healthcare needs of a growing and aging prison population, which accumulates vulnerability factors and suffers from higher disease prevalence than the general population. This study identifies the key factors associated with outpatient general practitioner (GP), nursing or psychiatric healthcare utilization (HCU) within prisons. Cross-sectional data systematically collected by the prison medical staff were obtained for a sample of 1664 adult prisoners of the Canton of Vaud, Switzerland, for the year 2011.

Disease profiles of detainees in the Canton of Vaud in Switzerland: gender and age differences in substance abuse, mental health and chronic health conditions.

Background: Literature on the disease profile of prisoners that differentiates by age and gender remains sparse. This study aimed to describe the health of correctional inmates in terms of substance abuse problems and mental and somatic health conditions, and compare it by gender and age.

Methods: This study examined cross-sectional data from the Canton of Vaud in Switzerland on the health conditions of detainees who were in prison on January 1, 2011 or entered prison in 2011.

Silicon micromachined ultrasonic scalpel for the dissection and coagulation of tissue.

This work presents a planar, longitudinal mode ultrasonic scalpel microfabricated from monocrystalline silicon wafers. Silicon was selected as the material for the ultrasonic horn due to its high speed of sound and thermal conductivity as well as its low density compared to commonly used titanium based alloys. Combined with a relatively high Young's modulus, a lighter, more efficient design for the ultrasonic scalpel can be implemented which, due to silicon batch manufacturing, can be fabricated at a lower cost.

Increased periodontal inflammation in women with preterm premature rupture of membranes.

Objectives: To evaluate possible differences in periodontal inflammatory, microbiological and clinical parameters between women with preterm premature rupture of membranes (PPROM) and controls with uncomplicated pregnancies.

Materials And Methods: Fifty-six women (32 test (PPROM) and 24 controls (uncomplicated pregnancies)) were examined at three time-points (T1: gestational weeks 20-35, T2: within 48 h after parturition, T3: 4-6 weeks after parturition). The examinations included assessment of the Periodontal Screening Index, collection of gingival crevicular fluid (GCF) and subgingival as well as vaginal bacterial sampling.

The potential association between gingival crevicular fluid inflammatory mediators and adverse pregnancy outcomes: a systematic review.

Objectives: The association between periodontal disease and adverse pregnancy outcomes (APO), primarily preterm birth (PTB), is still controversially discussed in the literature. Therefore, the aim of the present systematic review was to analyze the existing literature on the potential association between inflammatory mediators detected in gingival crevicular fluid (GCF) and APO.

Materials And Methods: MEDLINE (PubMed) and EMBASE databases were searched for entries up to April 2012 and studies were selected by two independent reviewers.

Dental visits, oral hygiene behaviour, and orthodontic treatment in Switzerland.

Since the first survey in 1992/93, the Swiss Health Survey (SHS) has been repeated every 5 years (1997, 2002 and 2007). In the present study, dental visits (dental care utilisation within the last 12 months), oral hygiene measures and the frequency of orthodontic treatments in the Swiss population in 2002 were examined and dental visits were compared with the years 1992/93, 1997 and 2007. Weighted data were analysed regarding different sociodemographic factors.

Biexciton emission and crystalline quality of ZnO nano-objects.

The design of cost-effective standards for the quality of nano-objects is currently a key issue toward their massive use for optoelectronic applications. The observation by photoluminescence of narrow excitonic and biexcitonic emission lines in semiconductor nanowires is usually accepted as evidence for high structural quality. Here, we perform time-resolved cathodoluminescence experiments on isolated ZnO nanobelts grown by chemical vapor deposition.

A new structural alert for benzimidazoles: 2,6-dimethylphenyl substituents increase mutagenic potential and time-dependent CYP3A4 inhibition risk.

A series of 2-[(2,6)-dimethylphenyl]benzimidazole analogs displayed strong potential for mutagenicity following metabolic activation in either TA98 or TA100 Salmonella typhimurium strains. The number of revertants was significantly reduced by replacing the 2,6-dimethylphenyl group with a 2,6-dichlorophenyl moiety. Time-dependent CYP3A4 inhibition was also observed with a compound containing a 2-[(2,6)-dimethylphenyl] benzimidazole ring, implying risk for this scaffold to generate reactive metabolites.

The symmetry of precession electron diffraction patterns.

The integrated intensity of the diffracted beams present on microdiffraction precession patterns can be used to infer the 'ideal' symmetry, i.e. the symmetry which takes into account both the position and the intensity of the diffracted beams on a diffraction pattern.

Core-shell Au@(TiO(2), SiO(2)) nanoparticles with tunable morphology.

A novel approach based on the Stöber method allows breaking of the symmetry of core-shell systems based on metallic core and metal oxide shell. By adjusting the proportion of the TiO(2) precursor with regard to the silica precursor, different morphologies of the particles have been obtained displacing the gold particle from center to eccentric positions leading to acorn-like and raspberry-like structure.

Dexamethasone-containing biodegradable superparamagnetic microparticles for intra-articular administration: physicochemical and magnetic properties, in vitro and in vivo drug release.

Compared with traditional drug solutions or suspensions, polymeric microparticles represent a valuable means to achieve controlled and prolonged drug delivery into joints, but still suffer from the drawback of limited retention duration in the articular cavity. In this study, our aim was to prepare and characterize magnetic biodegradable microparticles containing dexamethasone acetate (DXM) for intra-articular administration. The superparamagnetic properties, which result from the encapsulation of superparamagnetic iron oxide nanoparticles (SPIONs), allow for microparticle retention with an external magnetic field, thus possibly reducing their clearance from the joint.

EELS spectroscopy of iron fluorides and FeFx/C nanocomposite electrodes used in Li-ion batteries.

A new type of positive electrode for Li-ion batteries has been developed recently based on FeF3/C and FeF2/C nanocomposites. The microstructural and redox evolution during discharge and recharge processes was followed by electron energy loss spectroscopy (EELS) to determine the valence state of Fe by measuring the Fe L3 line energy shift and from Fe L3/L2 line intensity ratios. In addition, transition metal fluorides were found to be electron beam sensitive, and the effect of beam exposure on EELS spectra was also investigated.

The morphology of submicronsized core-shell latex particles: an electron microscopy study.

The core-shell structure of a range of acrylic-acrylic latexes has been investigated by combining different specimen preparation methods with transmission electron microscopy (TEM), dark-field scanning transmission electron microscopy (DSTEM) and low-voltage scanning electron microscopy (LV-SEM), including the first reported use of LV-SEM to observe composite latex particles at ambient and subambient temperatures. Spin-coating of liquid latex dispersions directly onto TEM grids or SEM stubs is shown to be a relatively straightforward mean of avoiding film formation during specimen preparation. In conjunction with double staining techniques, it has been found to be particularly convenient for characterizing the fine structure of particles with diameters down to below 100 nm.

Practical method for high-resolution imaging of polymers by low-voltage scanning electron microscopy.

Morphologic characterization of polymers by scanning electron microscopy (SEM) is often made difficult by their sensitivity to electron beam damage. We describe here a specimen preparation method for the imaging of polymer blends by low-voltage SEM (LV-SEM) that improves their stability in the electron beam and hence facilitates focusing and recording of high magnification images. Its application to nanosized core-shell latexes embedded in a polymethylmethacrylate matrix and semi-crystalline polypropylene/ethylene-propylene rubber blends is discussed.

Self-assembly of subnanometer-diameter single-wall MoS2 nanotubes.

We report on the synthesis, structure, and self-assembly of single-wall subnanometer-diameter molybdenum disulfide tubes. The nanotubes are up to hundreds of micrometers long and display diverse self-assembly properties on different length scales, ranging from twisted bundles to regularly shaped "furry" forms. The bundles, which contain interstitial iodine, can be readily disassembled into individual molybdenum disulfide nanotubes.

Theoretical and experimental limits of the analysis of III/V semiconductors using EELS.

The optimisation of acquisition conditions for EELS spectroscopy of Al(x)Ga(1-x)As heterostructures permits one to find the absolute concentration with a precision of better than delta = +/-0.02 and to detect changes in concentration of +/-0.01 for x = 0-0.