A randomized, controlled cross-over trial of dermally-applied lavender (lavandula angustifolia) oil as a treatment of agitated behaviour in dementia

Background: Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. Methods: 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants’ predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. Results: Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants’ affect. Conclusions: Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202

Cohort profile: the Cambridge City over-75s Cohort (CC75C).

The Cambridge City over-75s Cohort (CC75C), one of the largest and longest-running population-based studies of the oldest old, is celebrating its 21st birthday. Its origins and subsequent evolution into one of the UK's key ageing cohort studies lie in the collaboration of many distinguished researchers, and its ongoing importance owes much to the invaluable contribution made by its many committed participants

Virtual Texture Generated using Elastomeric Conductive Block Copolymer in Wireless Multimodal Haptic Glove.

Haptic devices are in general more adept at mimicking the bulk properties of materials than they are at mimicking the surface properties. This paper describes a haptic glove capable of producing sensations reminiscent of three types of near-surface properties: hardness, temperature, and roughness. To accomplish this mixed mode of stimulation, three types of haptic actuators were combined: vibrotactile motors, thermoelectric devices, and electrotactile electrodes made from a stretchable conductive polymer synthesized in our laboratory. This polymer consisted of a stretchable polyanion which served as a scaffold for the polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT). The scaffold was synthesized using controlled radical polymerization to afford material of low dispersity, relatively high conductivity (0.1 S cm-1), and low impedance relative to metals. The glove was equipped with flex sensors to make it possible to control a robotic hand and a hand in virtual reality (VR). In psychophysical experiments, human participants were able to discern combinations of electrotactile, vibrotactile, and thermal stimulation in VR. Participants trained to associate these sensations with roughness, hardness, and temperature had an overall accuracy of 98%, while untrained participants had an accuracy of 85%. Sensations could similarly be conveyed using a robotic hand equipped with sensors for pressure and temperature

The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies

Calibrationless Multi-coil Magnetic Resonance Imaging with Compressed Sensing

We present a method for combining the data retrieved by multiple coils of a Magnetic Resonance Imaging (MRI) system with the a priori assumption of compressed sensing to reconstruct a single image. The final image is the result of an optimization problem that only includes constraints based on fundamental physics (Maxwell's equations and the Biot-Savart law) and accepted phenomena (e.g. sparsity in the Wavelet domain). The problem is solved using an alternating minimization approach: two convex optimization problems are alternately solved, one with the Fast Iterative Shrinkage Threshold Algorithm (FISTA) and the other with the Primal-Dual Hybrid Gradient (PDHG) method. We show results on simulated data as well as data of the knee, brain, and ankle. In all cases studied, results from the new algorithm show higher quality and increased detail when compared to conventional reconstruction algorithms

Mutational and Structural Analysis of KIR3DL1 Reveals a Lineage-Defining Allotypic Dimorphism That Impacts Both HLA and Peptide Sensitivity

Killer Ig-like receptors (KIRs) control the activation of human NK cells via interactions with peptide-laden HLAs. KIR3DL1 is a highly polymorphic inhibitory receptor that recognizes a diverse array of HLA molecules expressing the Bw4 epitope, a group with multiple polymorphisms incorporating variants within the Bw4 motif. Genetic studies suggest that KIR3DL1 variation has functional significance in several disease states, including HIV infection. However, owing to differences across KIR3DL1 allotypes, HLA-Bw4, and associated peptides, the mechanistic link with biological outcome remains unclear. In this study, we elucidated the impact of KIR3DL1 polymorphism on peptide-laden HLA recognition. Mutational analysis revealed that KIR residues involved in water-mediated contacts with the HLA-presented peptide influence peptide binding specificity. In particular, residue 282 (glutamate) in the D2 domain underpins the lack of tolerance of negatively charged C-terminal peptide residues. Allotypic KIR3DL1 variants, defined by neighboring residue 283, displayed differential sensitivities to HLA-bound peptide, including the variable HLA-B*57:01-restricted HIV-1 Gag-derived epitope TW10. Residue 283, which has undergone positive selection during the evolution of human KIRs, also played a central role in Bw4 subtype recognition by KIR3DL1. Collectively, our findings uncover a common molecular regulator that controls HLA and peptide discrimination without participating directly in peptide-laden HLA interactions. Furthermore, they provide insight into the mechanics of interaction and generate simple, easily assessed criteria for the definition of KIR3DL1 functional groupings that will be relevant in many clinical applications, including bone marrow transplantation

Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics

Background Striatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment-seeking alcoholics (NTS). Methods Twenty-four SD and twenty-one NTS received two [11C]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then “clamped.” The alcohol clamp was started 5 min after scan start, with a linear increase in BrAC over 15 min to the target of 80 mg%, the legal threshold for intoxication. Target BrAC was maintained for 30 min. Voxel-wise binding potential (BPND) was estimated with MRTM2. Results IV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group. Conclusions Alcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD

Orally administered β-glucan attenuates the Th2 response in a model of airway hypersensitivity

β-Glucan is a polysaccharide that can be extracted from fungal cell walls. Wellmune WGP®, a preparation of β-1,3/1,6-glucans, is a dietary supplement that has immunomodulating properties. Here we investigated the effect WGP had on a mouse model of asthma. OVA-induced asthma in mice is characterized by infiltration of eosinophils into the lung, production of Th2 cytokines and IgE. Daily oral administration of WGP (400 µg) significantly reduced the influx of eosinophils into the lungs of OVA-challenged mice compared to control mice. In addition, WGP inhibited pulmonary production of Th2 cytokines (IL-4, IL-5, IL-13), however serum IgE levels were unaffected by WGP treatment. These data indicate that WGP could potentially be useful as an oral supplement for some asthma patients, however, it would need to be combined with therapies that target other aspects of the disease such as IgE levels. As such, further studies that examine the potential of WGP in combination with other therapies should be explored