Thoracic endometrial syndrome with unilateral exudative pleural effusion.

A woman in her 40s presented with exertional dyspnoea with an absence of haemoptysis, cough, fever and weight loss. The patient had a medical history of extensive endometriosis. Investigations revealed a large right-sided pleural effusion. The effusion was aspirated and was exudative in nature.A contrast-enhanced CT thorax was performed to help exclude dual pathology. The only positive finding was bilateral breast nodules, subsequently found to be benign fibroadenomas on histological analysis of biopsy samples.After malignancy was ruled out as a cause, the patient was referred for medical thoracoscopy for a biopsy and other investigations. Histology demonstrated the presence of endometrial tissue in the pleura and thereby confirmed the diagnosis of thoracic endometrial syndrome.Video-assisted thoracoscopic surgery repair of diaphragm and talc pleurodesis was carried out in an uncomplicated procedure and the patient was discharged with good recovery.

Radionuclide Imaging of the Neuroanatomical and Neurochemical Substrate of Cognitive Decline in Parkinson's Disease.

Cognitive impairment is a frequent manifestation of Parkinson's disease (PD), resulting in decrease in patients' quality of life and increased societal and economic burden. However, cognitive decline in PD is highly heterogenous and the mechanisms are poorly understood. Radionuclide imaging techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT) have been used to investigate the neurochemical and neuroanatomical substrate of cognitive decline in PD. These techniques allow the assessment of different neurotransmitter systems, changes in brain glucose metabolism, proteinopathy, and neuroinflammation in vivo in PD patients. Here, we review current radionuclide imaging research on cognitive deficit in PD with a focus on predicting accelerating cognitive decline. This research could assist in the development of prognostic biomarkers for patient stratification and have utility in the development of ameliorative or disease-modifying therapies targeting cognitive deficit in PD.

Differences in brain aging between sexes in Parkinson's disease.

Parkinson's disease (PD) is linked to faster brain aging. Male sex is associated with higher prevalence, severe symptoms, and a faster progression rate in PD. There remains a significant gap in understanding the function of sex in the process of brain aging in PD. The structural T1-weighted MRI-driven brain-predicted age difference (i.e., Brain-PAD: the actual age subtracted from the brain-predicted age) was computed in a group of 373 people with PD (mean age ± SD: 61.37 ± 9.81, age range: 33-85, 34% female) from the Parkinson's Progression Marker Initiative database using a robust brain-age estimation framework that was trained on 949 healthy subjects. Linear regression models were used to investigate the association between Brain-PAD and clinical variables in PD, stratified by sex. Males with Parkinson's disease (PD-M) exhibited a significantly higher mean Brain-PAD than their female counterparts (PD-F) (t(256) = 2.50, p = 0.012). In the propensity score-matched PD-M group (PD-M*), Brain-PAD was found to be associated with a decline in general cognition, a worse degree of sleep behavior disorder, reduced visuospatial acuity, and caudate atrophy. Conversely, no significant links were observed between these factors and Brain-PAD in the PD-F group. Having 'older' looking brains in PD-M than PD-F supports the idea that sex plays a vital function in PD, such that the PD mechanism may be different in males and females. This study has the potential to broaden our understanding of dissimilarities in brain aging between sexes in the context of PD.

Functional connectivity alterations in PTSD patients with suicidal ideation.

Post-traumatic stress disorder (PTSD) is a highly prevalent psychological disorder characterized by intense feelings of fear or helplessness after experiencing a traumatic event. PTSD is highly comorbid with mood disorders and patients are at increased risk for suicide. The present study aimed to identify neural connectivity alterations associated with suicidal ideation (SI) in PTSD patients by using resting-state functional magnetic resonance imaging. Voxel-to-voxel intrinsic connectivity was compared between PTSD patients with no (N-SI; N = 26) and high (H-SI; N = 7) SI. Region-to-voxel functional connectivity analysis was performed to identify the regions that contributed to intrinsic connectivity changes. H-SI patients had increased connectivity to various brain regions representing the central executive network, salience network, and default mode network in the frontal, temporal, and occipital lobes as well as subcortical structures involved in executive and limbic functioning, and motor systems. These results suggest SI is associated with large network-level alterations in PTSD patients and is not the result of neuronal abnormalities in any one specific area.

Influence of Cation Substitution on Cycling Stability and Fe-Cation Migration in Li3Fe3-xMxTe2O12 (M = Al, In) Cathode Materials.

Li3Fe3Te2O12 adopts a crystal structure, described in space group Pnnm, related to that of LiSbO3, in which Te6+, Fe3+, and Li+ cations reside in a partially ordered configuration within an hcp array of oxide ions. Chemical or electrochemical insertion of lithium is accompanied by a fully reversible migration of some of the Fe cations with an initial capacity of 120 mA h g-1 (2.85 Li per formula unit). Long-term cycling stability is limited by the facile reduction of Te6+ to elemental Te, which leads to cathode decomposition. Partial substitution of Fe by In suppresses Te6+ reduction, such that Li3Fe2InTe2O12 shows no sign of this cathode decomposition pathway, even after 100 cycles. In contrast, Al-for-Fe substitution is chemically limited to Li3Fe2.6Al0.4Te2O12 and appears to have almost no influence on cathode longevity. These features of the Li3Fe3-xMxTe2O12 system are discussed on the basis of a detailed structural analysis performed using neutron and synchrotron X-ray diffraction.

Direct Observation of Dynamic Lithium Diffusion Behavior in Nickel-Rich, LiNi0.8Mn0.1Co0.1O2 (NMC811) Cathodes Using Operando Muon Spectroscopy.

Ni-rich layered oxide cathode materials such as LiNi0.8Mn0.1Co0.1O2 (NMC811) are widely tipped as the next-generation cathodes for lithium-ion batteries. The NMC class offers high capacities but suffers an irreversible first cycle capacity loss, a result of slow Li+ diffusion kinetics at a low state of charge. Understanding the origin of these kinetic hindrances to Li+ mobility inside the cathode is vital to negate the first cycle capacity loss in future materials design. Here, we report on the development of operando muon spectroscopy (µSR) to probe the Å-length scale Li+ ion diffusion in NMC811 during its first cycle and how this can be compared to electrochemical impedance spectroscopy (EIS) and the galvanostatic intermittent titration technique (GITT). Volume-averaged muon implantation enables measurements that are largely unaffected by interface/surface effects, thus providing a specific characterization of the fundamental bulk properties to complement surface-dominated electrochemical methods. First cycle measurements show that the bulk Li+ mobility is less affected than the surface Li+ mobility at full depth of discharge, indicating that sluggish surface diffusion is the likely cause of first cycle irreversible capacity loss. Additionally, we demonstrate that trends in the nuclear field distribution width of the implanted muons during cycling correlate with those observed in differential capacity, suggesting the sensitivity of this µSR parameter to structural changes during cycling.

Anion-polarisation-directed short-range-order in antiperovskite Li2FeSO.

Short-range ordering in cation-disordered cathodes can have a significant effect on their electrochemical properties. Here, we characterise the cation short-range order in the antiperovskite cathode material Li2FeSO, using density functional theory, Monte Carlo simulations, and synchrotron X-ray pair-distribution-function data. We predict partial short-range cation-ordering, characterised by favourable OLi4Fe2 oxygen coordination with a preference for polar cis-OLi4Fe2 over non-polar trans-OLi4Fe2 configurations. This preference for polar cation configurations produces long-range disorder, in agreement with experimental data. The predicted short-range-order preference contrasts with that for a simple point-charge model, which instead predicts preferential trans-OLi4Fe2 oxygen coordination and corresponding long-range crystallographic order. The absence of long-range order in Li2FeSO can therefore be attributed to the relative stability of cis-OLi4Fe2 and other non-OLi4Fe2 oxygen-coordination motifs. We show that this effect is associated with the polarisation of oxide and sulfide anions in polar coordination environments, which stabilises these polar short-range cation orderings. We propose that similar anion-polarisation-directed short-range-ordering may be present in other heterocationic materials that contain cations with different formal charges. Our analysis illustrates the limitations of using simple point-charge models to predict the structure of cation-disordered materials, where other factors, such as anion polarisation, may play a critical role in directing both short- and long-range structural correlations.

A Propensity-Matched Comparison of Ischemic Brain Lesions on Postprocedural MRI in Endovascular versus Open Carotid Artery Reconstruction.

(1) Study purpose: The aim of our prospective single-center, matched case-control study was to compare the number and volume of acute ischemic brain lesions following carotid endarterectomy (CEA) versus carotid artery stenting (CAS) using a propensity-matched design. (2) Methods: Carotid bifurcation plaques were analyzed by using VascuCAP software on CT angiography (CTA) images. The number and volume of acute and chronic ischemic brain lesions were assessed on MRI scans taken 12-48 h after the procedures. Propensity score-based matching was performed at a 1:1 ratio to compare the ischemic lesions on postinterventional MR. (3) Results: A total of 107 patients (CAS, N = 33; CEA, N = 74) were included in the study. There were significant differences in smoking (p = 0.003), total calcification plaque volume (p = 0.004), and lengths of the lesion (p = 0.045) between the CAS and CEA groups. Propensity score matching resulted in 21 matched pairs of patients. Acute ischemic brain lesions were detected in ten patients (47.6%) of the matched CAS group and in three patients (14.2%) in the matched CEA group (p = 0.02). The volume of acute ischemic brain lesions was significantly larger (p = 0.04) in the CAS group than in the CEA group. New ischemic brain lesions were not associated with neurological symptoms in either group. (4) Conclusions: Procedure-related new acute ischemic brain lesions occurred significantly more frequently in the propensity-matched CAS group.

Hypermetabolic Cerebellar Connectome in Alzheimer's Disease.

Introduction: Regional hypermetabolism in Alzheimer's disease (AD), especially in the cerebellum, has been consistently observed but often neglected as an artefact produced by the commonly used proportional scaling procedure in the statistical parametric mapping. We hypothesize that the hypermetabolic regions are also important in disease pathology in AD. Methods: Using fluorodeoxyglucose (FDG)-positron emission tomography (PET) images from 88 AD subjects and 88 age-sex matched normal controls (NL) from the publicly available Alzheimer's Disease Neuroimaging Initiative database, we developed a general linear model-based classifier that differentiated AD patients from normal individuals (sensitivity = 87.50%, specificity = 82.95%). We constructed region-region group-wise correlation matrices and evaluated differences in network organization by using the graph theory analysis between AD and control subjects. Results: We confirmed that hypermetabolism found in AD is not an artefact by replicating it using white matter as the reference region. The role of the hypermetabolic regions has been further investigated by using the graph theory. The differences in betweenness centrality (BC) between AD and NL network were correlated with region weights of FDG PET-based AD classifier. In particular, the hypermetabolism in cerebellum was accompanied with higher BC. The brain regions with higher BC in AD network showed a progressive increase in FDG uptake over 2 years in prodromal AD patients (n = 39). Discussion: This study suggests that hypermetabolism found in AD may play an important role in forming the AD-related metabolic network. In particular, hypermetabolic cerebellar regions represent a good candidate for further investigation in altered network organization in AD.

Predicting cognitive decline in Parkinson's disease using FDG-PET-based supervised learning.

BackgroundCognitive impairment is a common symptom of Parkinson's disease (PD) that increases in risk and severity as the disease progresses. An accurate prediction of the risk of progression from the mild cognitive impairment (MCI) stage to the dementia (PDD) stage is an unmet clinical need.MethodsWe investigated the use of a supervised learning algorithm called the support vector machine (SVM) to retrospectively stratify patients on the basis of brain fluorodeoxyglucose-PET (FDG-PET) scans. Of 43 patients with PD-MCI according to the baseline scan, 23 progressed to PDD within a 5-year period, whereas 20 maintained stable MCI. The baseline scans were used to train a model, which separated patients identified as PDD converters versus those with stable MCI with 95% sensitivity and 91% specificity.ResultsIn an independent validation data set of 19 patients, the AUC was 0.73, with 67% sensitivity and 80% specificity. The SVM model was topographically characterized by hypometabolism in the temporal and parietal lobes and hypermetabolism in the anterior cingulum and putamen and the insular, mesiotemporal, and postcentral gyri. The performance of the SVM model was further tested on 2 additional data sets, which confirmed that the model was also sensitive to later-stage PDD (17 of 19 patients; 89% sensitivity) and dementia with Lewy bodies (DLB) (16 of 17 patients; 94% sensitivity), but not to normal cognition PD (2 of 17 patients). Finally, anti-PD medication status did not change the SVM classification of the other set of 10 patients with PD who were scanned twice, ON and OFF medication.ConclusionsThese results potentially indicate that the proposed FDG-PET-based SVM classifier has utility for providing an accurate prognosis of dementia development in patients with PD-MCI.

Schizophrenia-associated LRRTM1 regulates cognitive behavior through controlling synaptic function in the mediodorsal thalamus.

Reduced activity of the mediodorsal thalamus (MD) and abnormal functional connectivity of the MD with the prefrontal cortex (PFC) cause cognitive deficits in schizophrenia. However, the molecular basis of MD hypofunction in schizophrenia is not known. Here, we identified leucine-rich-repeat transmembrane neuronal protein 1 (LRRTM1), a postsynaptic cell-adhesion molecule, as a key regulator of excitatory synaptic function and excitation-inhibition balance in the MD. LRRTM1 is strongly associated with schizophrenia and is highly expressed in the thalamus. Conditional deletion of Lrrtm1 in the MD in adult mice reduced excitatory synaptic function and caused a parallel reduction in the afferent synaptic activity of the PFC, which was reversed by the reintroduction of LRRTM1 in the MD. Our results indicate that chronic reduction of synaptic strength in the MD by targeted deletion of Lrrtm1 functionally disengages the MD from the PFC and may account for cognitive, social, and sensorimotor gating deficits, reminiscent of schizophrenia.

In Situ Diffusion Measurements of a NASICON-Structured All-Solid-State Battery Using Muon Spin Relaxation.

In situ muon spin relaxation is demonstrated as an emerging technique that can provide a volume-averaged local probe of the ionic diffusion processes occurring within electrochemical energy storage devices as a function of state of charge. Herein, we present work on the conceptually interesting NASICON-type all-solid-state battery LiM2(PO4)3, using M = Ti in the cathode, M = Zr in the electrolyte, and a Li metal anode. The pristine materials are studied individually and found to possess low ionic hopping activation energies of ∼50-60 meV and competitive Li+ self-diffusion coefficients of ∼10-10-10-9 cm2 s-1 at 336 K. Lattice matching of the cathode and electrolyte crystal structures is employed for the all-solid-state battery to enhance Li+ diffusion between the components in an attempt to minimize interfacial resistance. The cell is examined by in situ muon spin relaxation, providing the first example of such ionic diffusion measurements. This technique presents an opportunity to the materials community to observe intrinsic ionic dynamics and electrochemical behavior simultaneously in a nondestructive manner.

The Vasomotor Response to Dopamine Is Altered in the Rat Model of l-dopa-Induced Dyskinesia.

BACKGROUND: Levodopa (l-dopa) is the frontline treatment for motor symptoms of Parkinson's disease. However, prolonged use of l-dopa results in a motor complication known as levodopa-induced dyskinesia (LID) in ~50% of patients over 5 years. OBJECTIVES: We investigated neurovascular abnormalities in a rat model of LID by examining changes in angiogenesis and dopamine-dependent vessel diameter changes. METHODS: Differences in striatal and nigral angiogenesis in a parkinsonian rat model (6-OHDA lesion) treated with 2 doses of l-dopa (saline, 2, and 10 mg/kg/day subcutaneous l-dopa treatment for 22 days) by 5-bromo-2'-deoxyuridine (BrdU)-RECA1 co-immunofluorescence. Difference in the vasomotor response to dopamine was examined with 2-photon laser scanning microscopy and Dodt gradient imaging. RESULTS: We found that the 10 mg/kg l-dopa dosing regimen induced LID in all animals (n = 5) and induced significant angiogenesis in the striatum and substantia nigra. In contrast, the 2 mg/kg treatment induced LID in 6 out of 12 rats and led to linearly increasing LID severity over the 22-day treatment period, making this a promising model for studying LID progression longitudinally. However, no significantly different level of angiogenesis was observed between LID versus non-LID animals. Dopamine-induced vasodilatory responses were exaggerated only in rats that show LID-like signs compared to the rest of groups. Additionally, in juvenile rats, we showed that DA-induced vasodilation is preceded by increased Ca2+ release in the adjacent astrocytes. CONCLUSION: This finding supports that astrocytic dopamine signaling controls striatal blood flow bidirectionally, and the balance is altered in LID. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Tracking wireworm burrowing behaviour in soil over time using 3D X-ray computed tomography.

BACKGROUND: Wireworms (larvae of the click beetle, Elateridae) are a significant agricultural pest, causing crop damage and reducing yields globally. Owing to the complex nature and opacity of the soil environment, research to investigate wireworm behaviour in situ has been scarce. X-ray computed tomography (CT) has previously been demonstrated as a powerful tool to independently visualise the 3D root system architecture, macroinvertebrate movement and distribution of burrow systems in soil, but not simultaneously within the same sample. In this study, we apply X-ray CT to visualise and quantify wireworms, their burrow systems and the root architecture of two contrasting crop species (Hordeum vulgare and Zea mays) in a soil pot experiment scanned at different time intervals. RESULTS: The majority of wireworm burrows were produced within the first 20 h post inoculation, suggesting that burrow systems are established quickly and persist at a similar volume. There was a significant difference in the volume of burrow systems produced by wireworms between the two crop species suggesting differences in wireworm behaviour elicited by crop species. There was no significant correlation between burrow volume and either root volume or surface area, indicating this behavioural difference is caused by factor(s) other than the mass of root systems. CONCLUSION: X-ray CT shows potential as a non-destructive technique to quantify the interaction of wireworms in the natural soil environment with crop roots, and aid the development of effective pest management strategies to minimise their negative impact on crop production. © 2020 Society of Chemical Industry.

p53 CRISPR Deletion Affects DNA Structure and Nuclear Architecture.

The TP53 gene is a key tumor suppressor. Although the tumor suppressor p53 was one of the first to be characterized as a transcription factor, with its main function potentiated by its interaction with DNA, there are still many unresolved questions about its mechanism of action. Here, we demonstrate a novel role for p53 in the maintenance of nuclear architecture of cells. Using three-dimensional (3D) imaging and spectral karyotyping, as well as super resolution microscopy of DNA structure, we observe significant differences in 3D telomere signatures, DNA structure and DNA-poor spaces as well gains or losses of chromosomes, between normal and tumor cells with CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-deleted or wild-type TP53. Additionally, treatment with Nutlin-3 results in differences in nuclear architecture of telomeres in wild-type but not in p53 knockout MCF-7 (Michigan Cancer Foundation-7) cells. Nutlin-3 binds to the p53-binding pocket of mouse double minute 2 (MDM2) and blocks the p53-MDM2 interaction. Moreover, we demonstrate that another p53 stabilizing small molecule, RITA (reactivation of p53 and induction of tumor cell apoptosis), also induces changes in 3D DNA structure, apparently in a p53 independent manner. These results implicate p53 activity in regulating nuclear organization and, additionally, highlight the divergent effects of the p53 targeting compounds Nutlin-3 and RITA.

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients.

Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID). Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data. Results: A significant interaction effect (imaging modality × medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed. Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.

Secondary Structural Changes in Proteins as a Result of Electroadsorption at Aqueous-Organogel Interfaces.

The electroadsorption of proteins at aqueous-organic interfaces offers the possibility to examine protein structural rearrangements upon interaction with lipophilic phases, without modifying the bulk protein or relying on a solid support. The aqueous-organic interface has already provided a simple means of electrochemical protein detection, often involving adsorption and ion complexation; however, little is yet known about the protein structure at these electrified interfaces. This work focuses on the interaction between proteins and an electrified aqueous-organic interface via controlled protein electroadsorption. Four proteins known to be electroactive at such interfaces were studied: lysozyme, myoglobin, cytochrome c, and hemoglobin. Following controlled protein electroadsorption onto the interface, ex situ structural characterization of the proteins by FTIR spectroscopy was undertaken, focusing on secondary structural traits within the amide I band. The structural variations observed included unfolding to form aggregated antiparallel ß-sheets, where the rearrangement was specifically dependent on the interaction with the organic phase. This was supported by MALDI ToF MS measurements, which showed the formation of protein-anion complexes for three of these proteins, and molecular dynamic simulations, which modeled the structure of lysozyme at an aqueous-organic interface. On the basis of these findings, the modulation of protein secondary structure by interfacial electrochemistry opens up unique prospects to selectively modify proteins.

Electrodeposition of Gold Nanostructures at the Interface of a Pickering Emulsion.

The controlled electrodeposition of nanoparticles at the surface of an emulsion droplet offers enticing possibilities in regards to the formation of intricate structures or fine control over the locus or duration of nanoparticle growth. In this work we develop electrochemical control over the spontaneous reduction of aqueous phase Au(III) by heterogeneous electron transfer from decamethylferrocene present in an emulsion droplet - resulting in the growth of nanoparticles. As gold is a highly effective conduit for the passage of electrical current, even on the nanoscale, the deposition significantly enhances the current response for the single electron transfer of decamethylferrocene when acting as a redox indicator. The nanostructures formed at the surface of the emulsion droplets were imaged by cryo-TEM, providing an insight into the types of structures that may form when stabilised by the interface alone, and how the structures are able to conduct electrons.