Corpora Amylacea of Brain Tissue from Neurodegenerative Diseases Are Stained with Specific Antifungal Antibodies

The origin and potential function of corpora amylacea (CA) remains largely unknown. Low numbers of CA are detected in the aging brain of normal individuals but they are abundant in the central nervous system of patients with neurodegenerative diseases. In the present study, we show that CA from patients diagnosed with Alzheimer's disease (AD) contain fungal proteins as detected by immunohistochemistry analyses. Accordingly, CA were labeled with different anti-fungal antibodies at the external surface, whereas the central portion composed of calcium salts contain less proteins. Detection of fungal proteins was achieved using a number of antibodies raised against different fungal species, which indicated cross-reactivity between the fungal proteins present in CA and the antibodies employed. Importantly, these antibodies do not immunoreact with cellular proteins. Additionally, CNS samples from patients diagnosed with amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) also contained CA that were immunoreactive with a range of antifungal antibodies. However, CA were less abundant in ALS or PD patients as compared to CNS samples from AD. By contrast, CA from brain tissue of control subjects were almost devoid of fungal immunoreactivity. These observations are consistent with the concept that CA associate with fungal infections and may contribute to the elucidation of the origin of CAThe financial support of Fundación ONCE (Organización Nacional de Ciegos Españoles) is acknowledged. We acknowledge an institutional grant to Centro de Biología Molecular “Severo Ochoa” from the Fundación Ramón Arece

Laue Lens Development for Hard X-rays (>60 keV)

Results of reflectivity measurements of mosaic crystal samples of Cu (111) are reported. These tests were performed in the context of a feasibility study of a hard X-ray focusing telescope for space astronomy with energy passband from 60 to 600 keV. The technique envisaged is that of using mosaic crystals in transmission configuration that diffract X-rays for Bragg diffraction (Laue lens). The Laue lens assumed has a spherical shape with focal length $f$. It is made of flat mosaic crystal tiles suitably positioned in the lens. The samples were grown and worked for this project at the Institute Laue-Langevin (ILL) in Grenoble (France), while the reflectivity tests were performed at the X-ray facility of the Physics Department of the University of Ferrara.Comment: 6 pages, 12 figures, accepted for publication in IEEE Transactions on Nuclear Scienc

Distal Forearm Replantation Rehabilitation - Case Review

Actualmente, o desafio da reimplantação do membro superior pós-amputação tornou-se uma realidade alcançável e minuciosamente aperfeiçoada nas últimas décadas, e em permanente evolução. A opção cirúrgica de reimplantação deve ter em conta não apenas a análise exclusiva da viabilidade do reimplante, mas, fundamentalmente o seu potencial de recuperação funcional a longo prazo. Apresenta-se o caso clínico de um jovem de 18 anos, fumador, transferido do Hospital do Barreiro, vítima de acidente de trabalho, com traumatismo por corte, do qual resultou amputação distal do antebraço direito. O tempo de isquemia quente foi de 4horas, tendo sido submetido a cirurgia de reimplantação conjunta por Ortopedia e Cirurgia Plástica e Reconstrutiva (CPR) para reimplantação. Na sequência da cirurgia, foi precocemente referenciado a Medicina Física e de Reabilitação (MFR), realizando um programa de reabilitação funcional sequencial. Este trabalho visa enfatizar a importância do papel da MFR num precoce, criterioso e extenso programa de reabilitação, factor fundamental na recuperação funcional e prognóstico a longo prazo destas lesões e prevenção de complicações

Combined NMDA Inhibitor Use in a Patient With Multisubstance-induced Psychotic Disorder

This document is an Accepted Manuscript reprinted from Journal of Addiction Medicine, Vol. 12 (3): 247-251, May 2018, with permission of Kluwer Law International. Under embargo until 1 May 2019. The Version of Record is available online at DOI: https://doi.org/10.1097/ADM.0000000000000390: Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders. CASE REPORT: We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists. At age 23, he developed social withdrawal after being assaulted by a stranger, but did not consult psychiatrists until age 26; during this period, he was using internet-purchased methoxetamine and ketamine, and was persecutory, irritable, suspicious, and insomniac and discontinued all received medical prescriptions. He added dextromethorphan to his list of used substances. At age 31, while using phencyclidine, and, for the first time, methoxphenidine, he developed a religious delusion, involving God calling him to reach Him, and the near-death experiences ensured by NMDA antagonists backed his purpose. He received Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnosis of multisubstance-induced psychotic disorder and was hospitalized 8 times, 6 of which after visiting the emergency room due to the development of extreme anguish, verbal and physical aggression, and paranoia. He reportedly used methoxphenidine, methoxyphencyclidine, ethylnorketamine, norketamine, and deschlorketamine, to achieve near-death experiences, and eventually to reach God in heavens. CONCLUSIONS: This case points to the need for better control of drugs sold on the internet. It also illustrates that people using NMDA antagonists may present clinical pictures indistinguishable from those of major psychoses and are likely to be misdiagnosed.Peer reviewe

Polarisation measurements with a CdTe pixel array detector for Laue hard X-ray focusing telescopes

Polarimetry is an area of high energy astrophysics which is still relatively unexplored, even though it is recognized that this type of measurement could drastically increase our knowledge of the physics and geometry of high energy sources. For this reason, in the context of the design of a Gamma-Ray Imager based on new hard-X and soft gamma ray focusing optics for the next ESA Cosmic Vision call for proposals (Cosmic Vision 2015-2025), it is important that this capability should be implemented in the principal on-board instrumentation. For the particular case of wide band-pass Laue optics we propose a focal plane based on a thick pixelated CdTe detector operating with high efficiency between 60-600 keV. The high segmentation of this type of detector (1-2 mm pixel size) and the good energy resolution (a few keV FWHM at 500 keV) will allow high sensitivity polarisation measurements (a few % for a 10 mCrab source in 106s) to be performed. We have evaluated the modulation Q factors and minimum detectable polarisation through the use of Monte Carlo simulations (based on the GEANT 4 toolkit) for on and off-axis sources with power law emission spectra using the point spread function of a Laue lens in a feasible configuration.Comment: 10 pages, 6 pages. Accepted for publication in Experimental Astronom

Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis

Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patientsThe financial support of Fundación ONCE (Organización Nacional de Ciegos Españoles) is acknowledged. We acknowledge an institutional grant to Centro de Biología Molecular “Severo Ochoa” from the Fundación Ramón Arece

The prevalence and topography of spinal cord demyelination in multiple sclerosis: a retrospective study

Spinal cord pathology is a major determinant of irreversible disability in progressive multiple sclerosis. The demyelinated lesion is a cardinal feature. The well-characterised anatomy of the spinal cord and new analytic approaches allows the systematic study of lesion topography and its extent of inflammatory activity unveiling new insights into disease pathogenesis. We studied cervical, thoracic, and lumbar spinal cord tissue from 119 pathologically confirmed multiple sclerosis cases. Immunohistochemistry was used to detect demyelination (PLP) and classify lesional inflammatory activity (CD68). Prevalence and distribution of demyelination, staged by lesion activity, was determined and topographical maps were created to identify patterns of lesion prevalence and distribution using mixed models and permutation-based voxelwise analysis. 460 lesions were observed throughout the spinal cord with 76.5% of cases demonstrating at least 1 lesion. The cervical level was preferentially affected by lesions. 58.3% of lesions were inflammatory with 87.9% of cases harbouring at least 1 inflammatory lesion. Topographically, lesions consistently affected the dorsal and lateral columns with relative sparing of subpial areas in a distribution mirroring the vascular network. The presence of spinal cord lesions and the proportion of active lesions related strongly with clinical disease milestones, including time from onset to wheelchair and onset to death. We demonstrate that spinal cord demyelination is common, highly inflammatory, has a predilection for the cervical level, and relates to clinical disability. The topography of lesions in the dorsal and lateral columns and relative sparing of subpial areas points to a role of the vasculature in lesion pathogenesis, suggesting short-range cell infiltration from the blood and signaling molecules circulating in the perivascular space incite lesion development. These findings challenge the notion that end-stage progressive multiple sclerosis is ‘burnt out’ and an outside-in lesional gradient predominates in the spinal cord. Taken together, this study provides support for long-term targeting of inflammatory demyelination in the spinal cord and nominates vascular dysfunction as a potential target for new therapeutic approaches to limit irreversible disability

The Role of Intense Upper Hybrid Resonance Emissions in the Generation of Saturn Narrowband Emission

Twenty high-inclination ring-grazing orbits occurred in the final period of the Cassini mission. These orbits intercepted a region of intense Z-mode and narrowband (NB) emission (Ye et al., 2010, ) along with isolated, intense upper hybrid resonance (UHR) emissions that are often associated with NB source regions. We have singled out such UHR emission seen on earlier Cassini orbits that also lie near the region crossed by the ring-grazing orbits. These previous orbits are important because Cassini electron phase-space distributions are available and dispersion analysis can be performed to better understand the free energy source and instability of the UHR emission. We present an example of UHR emission on a previous orbit that is similar to that observed during the ring-grazing orbits. Analysis of the observed plasma distribution of the previous orbit leads us to conclude that episodes of UHR emission and NB radiation observed during the ring-grazing orbits are likely due to plasma distributions containing loss cones, temperature anisotropies, and strong density gradients near the ring plane. Z-mode emissions associated with UHR and NB emission can be in Landau resonance with electrons to produce scattering or acceleration (Woodfield et al., 2018, https://doi.org/10.1038/s41467-018-07549-4)