Serum dietary fatty acids and coronary heart disease risk - A nested case-control-study within the CARLA cohort.

BACKGROUND AND AIMS: Diet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk. METHODS AND RESULTS: The CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case-control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found. CONCLUSION: Our results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.

The mitochondrial protein TCAIM regulates activation of T cells and thereby promotes tolerance induction of allogeneic transplants.

Primary T cell activation and effector cell differentiation is required for rejection of allogeneic grafts in naïve recipients. It has become evident, that mitochondria play an important role for T cell activation. Expression of several mitochondrial proteins such as TCAIM (T cell activation inhibitor, mitochondrial) is down-regulated upon T cell receptor triggering. Here we report that TCAIM inhibited spontaneous development of memory and effector T cells. CD4(+) T cells from Tcaim knock-in (KI) mice showed reduced activation, cytokine secretion and proliferation in vitro. Tcaim KI T cells tolerated allogeneic skin grafts upon transfer into Rag-1 KO mice. CD4(+) and CD8(+) T cells from these mice did not infiltrate skin grafts and kept a naïve or central memory phenotype, respectively. They were unable to acquire effector phenotype and functions. TCAIM altered T cell activation-induced mitochondrial distribution and reduced mitochondrial reactive oxygen species (mROS) production. Thus, TCAIM controls T cell activation and promotes tolerance induction probably by regulating TCR-mediated mitochondrial distribution and mROS production.

Treating canine atopic dermatitis with unsaturated fatty acids: the role of mast cells and potential mechanisms of action.

Canine atopic dermatitis (CAD) is an inflammatory skin disorder that is characterized by pruritus and associated cutaneous changes. Treatment interventions include allergen avoidance, allergen-specific immunotherapy as well as a symptomatic therapy using glucocorticoids and antihistamines. In addition, a dietary intervention using polyunsaturated fatty acids (PUFA) has been shown to alleviate symptoms in some dogs. Although the beneficial effects of PUFA in the treatment of CAD have been known for several years, their mode of action remains unclear. This review discusses the evidential basis of the therapeutic use of dietary PUFA in the treatment of CAD. Particular emphasis will be placed on the role of cutaneous mast cells. In addition, recent evidence from in vitro studies on the regulation of mast cell exocytosis will be used to build a mechanistic model of the active principle of PUFA. It is proposed that dietary PUFA are integrated into mast cell membranes resulting in a reorganization of membrane microdomains. This may then be accompanied by functional changes of membrane-associated proteins such as the phospholipases D (PLD), enzymes having an important impact on mast cell exocytosis processes.

Biochemical and haematological profile of pheasant hens during the laying period.

The present paper provides new experimental data on the biochemical and haematological profile of blood in pheasant hens, and points out the changes in both biochemical and haematological parameters that occur during the laying period. Significant effects of egg laying on both the biochemical and the haematological blood parameters of pheasant hens were found. Biochemical analyses revealed a significant increase in the metabolites cholesterol, uric acid, lactate, the enzyme aspartate aminotransferase (AST) and the minerals calcium and phosphorous, as well as a significant decrease in total protein, albumin and glucose in the course of the laying period. Haematological analyses revealed a significant increase in the count of leukocytes, lymphocytes, eosinophils, basophils and monocytes due to egg laying. In addition, the erythrocyte count and haemoglobin content significantly decreased in the middle of the laying period and then rebounded at the end of the laying period. The haematocrit content gradually decreased till the end of the laying period. All together, the results of this study underline the impact of the reproduction status of pheasant hens on basic blood parameters. The biochemical and haematological values presented in this study may be of help in assessing disease conditions in laying pheasant hens.

Drug-related deaths at Australian music festivals.

BACKGROUND: Illicit drug use is overrepresented in music festival attendees compared with the general population. Drug use often involves a wide range of substances with the potential to cause drug toxicity. Law enforcement-centred strategies intended to deter drug use and supply at these mass gatherings have been implemented throughout Australia. However, many have been criticised for their lack of effectiveness, with evidence suggesting that they can inadvertently increase the risk of drug harm. Drug deaths are often multifactorial, providing added challenges in the development of prevention strategies. This study aimed to determine the frequency of deaths involving alcohol and other drugs at music festivals in Australia and to identify potential risk factors that may inform future harm reduction strategies. METHODS: A descriptive case series study was conducted using the National Coronial Information System (NCIS) to investigate drug-related deaths at music festivals throughout Australia between 1 July 2000 (Queensland from 1 January 2001) and 31 December 2019, using a list of keywords comprising music festival names and terms. RESULTS: There were 64 deaths, of which most involved males (73.4%) aged in their mid-20s (range 15-50 years). Drug toxicity was the most common primary cause of death (46.9%) followed by external injuries (37.5%). The drug most commonly detected or reported as being used was MDMA (65.6%), followed by alcohol (46.9%) and cannabis (17.2%), with most cases reporting the use of two or more drugs (including alcohol) and 36% reporting a history of drug misuse in the coroner's findings. Most deaths were unintentional, with less than a fifth of cases (17.2%) involving intentional self-harm. Clinical intervention was involved in 64.1% of cases and most festivals occurred in inner city locations (59.4%). CONCLUSIONS: The findings suggest that drug-related deaths at music festivals in Australia typically involve young people using multiple illicit substances in combination with alcohol. Most are unintentional and could potentially be prevented through the implementation of a range of harm reduction strategies, including mobile medical care, drug checking services, and increased consumer education and awareness.

Quasiballistic transport of Dirac fermions in a Bi2Se3 nanowire.

Quantum coherent transport of surface states in a mesoscopic nanowire of the three-dimensional topological insulator Bi(2}Se(3) is studied in the weak-disorder limit. At very low temperatures, many harmonics are evidenced in the Fourier transform of Aharonov-Bohm oscillations, revealing the long phase coherence length of spin-chiral Dirac fermions. Remarkably, from their exponential temperature dependence, we infer an unusual 1/T power law for the phase coherence length L(φ)(T). This decoherence is typical for quasiballistic fermions weakly coupled to their environment.

Evidence for triplet superconductivity in a superconductor-ferromagnet spin valve.

We have studied the dependence of the superconducting (SC) transition temperature on the mutual orientation of magnetizations of Fe1 and Fe2 layers in the spin valve system CoO(x)/Fe1/Cu/Fe2/Pb. We find that this dependence is nonmonotonic when passing from the parallel to the antiparallel case and reveals a distinct minimum near the orthogonal configuration. The analysis of the data in the framework of the SC triplet spin valve theory gives direct evidence for the long-range triplet superconductivity arising due to noncollinearity of the two magnetizations.

TOPAS: an innovative proton Monte Carlo platform for research and clinical applications.

PURPOSE: While Monte Carlo particle transport has proven useful in many areas (treatment head design, dose calculation, shielding design, and imaging studies) and has been particularly important for proton therapy (due to the conformal dose distributions and a finite beam range in the patient), the available general purpose Monte Carlo codes in proton therapy have been overly complex for most clinical medical physicists. The learning process has large costs not only in time but also in reliability. To address this issue, we developed an innovative proton Monte Carlo platform and tested the tool in a variety of proton therapy applications. METHODS: Our approach was to take one of the already-established general purpose Monte Carlo codes and wrap and extend it to create a specialized user-friendly tool for proton therapy. The resulting tool, TOol for PArticle Simulation (TOPAS), should make Monte Carlo simulation more readily available for research and clinical physicists. TOPAS can model a passive scattering or scanning beam treatment head, model a patient geometry based on computed tomography (CT) images, score dose, fluence, etc., save and restart a phase space, provides advanced graphics, and is fully four-dimensional (4D) to handle variations in beam delivery and patient geometry during treatment. A custom-designed TOPAS parameter control system was placed at the heart of the code to meet requirements for ease of use, reliability, and repeatability without sacrificing flexibility. RESULTS: We built and tested the TOPAS code. We have shown that the TOPAS parameter system provides easy yet flexible control over all key simulation areas such as geometry setup, particle source setup, scoring setup, etc. Through design consistency, we have insured that user experience gained in configuring one component, scorer or filter applies equally well to configuring any other component, scorer or filter. We have incorporated key lessons from safety management, proactively removing possible sources of user error such as line-ordering mistakes. We have modeled proton therapy treatment examples including the UCSF eye treatment head, the MGH stereotactic alignment in radiosurgery treatment head and the MGH gantry treatment heads in passive scattering and scanning modes, and we have demonstrated dose calculation based on patient-specific CT data. Initial validation results show agreement with measured data and demonstrate the capabilities of TOPAS in simulating beam delivery in 3D and 4D. CONCLUSIONS: We have demonstrated TOPAS accuracy and usability in a variety of proton therapy setups. As we are preparing to make this tool freely available for researchers in medical physics, we anticipate widespread use of this tool in the growing proton therapy community.

Magnetoresistance of rolled-up Fe3Si nanomembranes.

Magnetotransport of individual rolled-up Fe(3)Si nanomembranes is investigated in a broad temperature range from 4.2 K up to 300 K in pulsed magnetic fields up to 55 T. The observed magnetoresistance (MR) has the following pronounced features: (i) MR is negative in the investigated intervals of temperature and magnetic field; (ii) its magnitude increases linearly with the magnetic field in a low-field region and reveals a gradual trend to saturation when the magnetic field increases; (iii) the MR effect becomes more pronounced with increasing temperature. These dependences of MR on the magnetic field and temperature are in line with predictions of the spin-disorder model of the spin-flip s-d interaction assisted with creation or annihilation of magnons, which is expected above a certain critical temperature. Comparison of the MR features in rolled-up and planar samples reveals a substantial increase of the critical temperature in the rolled-up tube, which is attributed to a new geometry and internal strain arising in the rolled-up nanomembranes, influencing the electronic and magnetic properties of the material.

TGF-ß signaling in T cells is not essential for Th17 cell development in the mouse.

Th17 cells are potent pro-inflammatory effectors crucial for defense against extracellular bacteria. However, in this context and in the context of autoimmune disorders Th17 cells have been demonstrated to be key contributors to destructive pathological mechanism. A number of trials report TGF-beta to be involved in Th17 cell development. Nevertheless, to date, the role that TGF-beta plays in Th17 cell generation remains unclear. In this paper we highlight the role of TGF-beta in Th17 cell development in the mouse. The effects of likewise T cell specific over-expression of TGF-beta or inhibition of TGF-beta signal transduction in these cells on Th17 cell development were investigated by means of transgenic mouse models. The T cell specific insensitivity to TGF-beta does not prevent Th17 cell development ex vivo or in vitro in the murine system. In contrast, stimulation of T cells over-expressing TGF-beta actually results in decreased Th17 cell numbers in comparison to the wild type. Thus, our data indicate that TGF-beta signaling in T cells is dispensable or even inhibitory for generation of Th17 cells in the mouse. Moreover, we could show TGF-beta to inhibit a LPS driven Th1 cell development suggesting the cytokine to act as an indirect effector in Th17 cell differentiation.

Precise control of thermal conductivity at the nanoscale through individual phonon-scattering barriers.

The ability to precisely control the thermal conductivity (kappa) of a material is fundamental in the development of on-chip heat management or energy conversion applications. Nanostructuring permits a marked reduction of kappa of single-crystalline materials, as recently demonstrated for silicon nanowires. However, silicon-based nanostructured materials with extremely low kappa are not limited to nanowires. By engineering a set of individual phonon-scattering nanodot barriers we have accurately tailored the thermal conductivity of a single-crystalline SiGe material in spatially defined regions as short as approximately 15 nm. Single-barrier thermal resistances between 2 and 4 x 10(-9) m(2) K W(-1) were attained, resulting in a room-temperature kappa down to about 0.9 W m(-1) K(-1), in multilayered structures with as little as five barriers. Such low thermal conductivity is compatible with a totally diffuse mismatch model for the barriers, and it is well below the amorphous limit. The results are in agreement with atomistic Green's function simulations.

Manifestation of new interference effects in a superconductor-ferromagnet spin valve.

Superconductor-ferromagnet (S/F) spin valve effect theories based on the S/F proximity phenomenon assume that the superconducting transition temperature Tc of F1/F2/S or F1/S/F2 trilayers for parallel magnetizations of the F1 and F2 layers (T(c)(P)) are smaller than for the antiparallel orientations (T(c)(AP)). Here, we report for CoOx/Fe1/Cu/Fe2/In multilayers with varying Fe2-layer thickness the sign-changing oscillating behavior of the spin valve effect ΔT(c) = T(c)(AP) - T(c)(P). We observe the full direct effect with T(c)(AP) > T(c)(P) for Fe2-layer thickness d(Fe2) < 1 nm and the full inverse (T(c)(AP) < T(c((P)) effect for d(Fe2) ≥ 1 nm. Interference of Cooper pair wave functions reflected from both surfaces of the Fe2 layer appear as the most probable reason for the observed behavior of ΔT(c).

Iron filled carbon nanotubes as novel monopole-like sensors for quantitative magnetic force microscopy.

We present a novel ultrahigh stability sensor for quantitative magnetic force microscopy (MFM) based on an iron filled carbon nanotube. In contrast to the complex magnetic structure of conventional MFM probes, this sensor constitutes a nanomagnet with defined properties. The long iron nanowire can be regarded as an extended dipole of which only the monopole close to the sample surface is involved in the imaging process. We demonstrate its potential for high resolution imaging. Moreover, we present an easy routine to determine its monopole moment and prove that this calibration, unlike other approaches, is universally applicable. For the first time this enables straightforward quantitative MFM measurements.

Acute alcohol use in Australian coronial suicide cases, 2010-2015.

BACKGROUND: Acute use of alcohol is a robust risk factor for suicide, reported in approximately one- to two-fifths of suicide cases. Comparisons of risk factors between suicides with and without prior acute alcohol consumption have not been investigated in Australia. This study addresses the gap by examining individual factors (age, sex, employment status, method of suicide) and environmental factors (month of death, jurisdiction) between alcohol and non-alcohol suicide. METHODS: Data for all suicide deaths (aged 15 and over) in Australia were obtained from the National Coronial Information System (NCIS). Blood alcohol concentrations (BAC) were extracted from coronial reports, along with demographic information. Alcohol consumption prior to suicide was assumed if BAC ≥ 0.05 g/100 mL. We compared case characteristics between alcohol related and non-alcohol related suicides using logistic regression. RESULTS: 26.7% of suicide deaths in Australia had a BAC ≥ 0.05 g/100 mL. Alcohol use prior to suicide was associated with male gender (adjusted odds ratio [AOR]: 1.14, 95% confidence interval [95%CI]: 1.03, 1.26), being aged between 35-44 years (AOR: 1.26, 95%CI: 1.08, 1.46) and hangings (AOR: 1.53, 95%CI: 1.08, 1.46). Mean suicides per month over the timeframe demonstrated significant seasonality. Mean counts per month for alcohol related suicides peaked in December, compared to a peak in September for non-alcohol related suicides. CONCLUSIONS: This study highlights differences between alcohol related and non-alcohol related suicides including sex, age, method of death, time of year and location within Australia. Targeting alcohol related suicide should be a key priority in comprehensive suicide prevention strategies.

Epitaxial Fe3Si films on GaAs(100) substrates by means of electron beam evaporation.

This paper presents results on the preparation, structural, electrical and magnetic properties of Fe(3)Si films as a representative for a Heusler alloy-like compound which are known as half-metallic materials with ferromagnetic behaviour. The films have been prepared by means of ultra-high vacuum (UHV) electron beam evaporation with the aim of achieving epitaxial growth on GaAs(100) substrates. The main focus of this work is the structural characterization of the Fe(3)Si films grown on GaAs by means of high resolution transmission electron microscopy (TEM) to confirm the epitaxial growth. For Fe(3)Si with a composition in the vicinity of stoichiometry an almost lattice-matched growth on GaAs(001) has been observed characterized by a high crystalline quality and a good interface perfection. Besides the studies on cross-sectional samples by TEM data from reflection high energy electron diffraction (RHEED) and x-ray diffraction (XRD) were also included into the discussion. The electrical and magnetic parameters of the films studied are found to be in good agreement with data reported for the best Fe(3)Si molecular beam epitaxy (MBE) layers. As evidenced by x-ray diffraction, transmission electron microscopy, resistivity and magnetic measurements, we find an optimum growth temperature of 280-350 degrees C to obtain ferromagnetic layers with high crystal and interface perfection as well as a high degree of atomic ordering.

Structural and magnetic properties of an InGaAs/Fe3Si superlattice in cylindrical geometry.

The structure and magnetic properties of an InGaAs/Fe(3)Si superlattice in a cylindrical geometry are investigated by electron microscopy techniques, x-ray diffraction and magnetometry. To form a radial superlattice, a pseudomorphic InGaAs/Fe(3)Si bilayer has been released from its substrate self-forming into rolled-up microtubes. Oxide-free interfaces as well as areas of crystalline bonding are observed and an overall lattice mismatch between succeeding layers is determined. The cylindrical symmetry of the final radial superlattice shows a significant effect on the magnetization behavior of the rolled-up layers.

Vasoplegia in patients with sepsis and septic shock: pathways and mechanisms.

Sepsis is one of the most frequent causes of death among patients in intensive care units. Many therapeutic strategies have been assessed without the desired success rates. A key risk factor for death is hypotension due to vasodilatation with vascular hyposensitivity. However, the pathways underlying this process remain unclear. Endotoxemia induces inflammatory mediators, and this is followed by vasoplegia and decreased cardiac contractility. Although inhibition of these mediators diminishes mortality rates in animal models, this phenomenon has not been confirmed in humans. Downregulation of vasoconstrictive receptors such as angiotensin receptors, adrenergic and vasopressin receptors is seen in sepsis, which is associated with a hyporesponsiveness to vasoconstrictive mediators. Animal studies have verified that receptor downregulation is linked to the above-mentioned inflammatory mediators. Anti-inflammatory therapy with glucocorticoids reportedly improves responsiveness to catecholamines with higher survival in rats, although this has not been shown to be clinically significant in humans. Hence, there is an urgent need for in-depth studies investigating the underlying mechanisms of vasoplegia to allow for development of effective therapeutic strategies for the treatment of sepsis.

Weakly-coupled quasi-1D helical modes in disordered 3D topological insulator quantum wires.

Disorder remains a key limitation in the search for robust signatures of topological superconductivity in condensed matter. Whereas clean semiconducting quantum wires gave promising results discussed in terms of Majorana bound states, disorder makes the interpretation more complex. Quantum wires of 3D topological insulators offer a serious alternative due to their perfectly-transmitted mode. An important aspect to consider is the mixing of quasi-1D surface modes due to the strong degree of disorder typical for such materials. Here, we reveal that the energy broadening γ of such modes is much smaller than their energy spacing Δ, an unusual result for highly-disordered mesoscopic nanostructures. This is evidenced by non-universal conductance fluctuations in highly-doped and disordered Bi2Se3 and Bi2Te3 nanowires. Theory shows that such a unique behavior is specific to spin-helical Dirac fermions with strong quantum confinement, which retain ballistic properties over an unusually large energy scale due to their spin texture. Our result confirms their potential to investigate topological superconductivity without ambiguity despite strong disorder.

Pulse cytophotometric analysis of cell cycle perturbation with bleomycin in vitro.

The kinetic response of a human lymphoma cell line to bleomycin has been analyzed, using an ICP-11 pulse cytophotometer. Bleomycin induced a delay of the cell-cycle traverse in G2 phase, the extent and recovery of which depended on drug concentration, exposure time, and cell cycle stage where treatment was applied. Different phase sensitivity for lethal damage (G2 phase) and kinetic response (early S phase) were documented. Recovery from G2 block did not predict for unimpaired reproductive capacity.

Enhanced cell killing through the use of cell kinetics-directed treatment schedules for two-drug combinations in vitro.

Kinetics-directed drug treatment schedules were tested in Chinese hamster ovary cells. Ten hr after treatment with 1,2:5,6-dianhydrogalactitol (DAG) (at a dose lethal to less than 5% of the cells), a 150% enrichment of cells into the S phase of the cell cycle was observed. This blockade in S phase was reversible and was followed at 18 hr after an exposure to DAG by a 200% increase in the fraction of cells in the G2-M phases of the cell cycle. Bleomycin, known to be most effective against G2 + M cells, had the greatest effect on cell killing when administered at that time. Rapid analysis by flow microfluorometry techniques was used to determine the DAG-induced kinetics changes, thus allowing treatment with the second drugs at the most opportune time. The DAG-induced kinetics changes were also demonstrated in a line of human adenocarcinoma of the stomach in vitro and in Ehrlich ascites tumor cells in vivo. In all cases, the enrichment of cells into S phase was reversible at the doses used and was followed by a reversible blockade in G2-M.