Quantitative dopamine transporter imaging assessment in Parkinson's disease patients carrying GBA gene mutations compared with idiopathic PD patients: A case-control study.

BACKGROUND: Genetic risk factors impact around 15% of Parkinson's disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative-based data, various studies have been published on GBA-PD cohorts which suggested possible differences in dopaminergic nigrostriatal denervation pattern, particularly in caudate and putamen nuclei. METHODS: This retrospective study included two consecutive homogenous cohorts of GBA-PD and idiopathic (I-PD) patients. Each consecutive GBA-PD patient has been matched with a 1:1 pairing method with a consecutive I-PD subject according to age, age at disease onset, sex, Hoehn & Yahr (H&Y) staging scale and comorbidity level (CCI). Semiquantitative volumetric data by the DaTQUANTTM software integrated in the DaTSCAN exam performed at time of the diagnosis (SPECT imaging performed according to current guidelines of I-123 FPCIT SPECT imaging) were extrapolated. Bilateral specific binding ratios (SBR) at putamen and caudate levels were calculated, using the occipital lobes uptake. The Mann-Whitney test was performed to compare the two cohorts while the Spearman's test was used to find correlations between motor and volumetric data in each group. Bonferroni correction was used to account for multiple comparisons. RESULTS: Two cohorts of 25 patients each (GBA-PD and I-PD), were included. By comparing GBA-PD and I-PD patients, lower SBR values were found in the most affected anterior putamen and left caudate of the GBA-PD cohort. Furthermore, in the GBA-PD cohort the SBR of the most affected posterior putamen negatively correlated with the H&Y scale. However, none of these differences or correlations remained significant after Bonferroni correction for multiple comparisons. CONCLUSIONS: We observed differences in SBR values in GBA-PD patients compared with I-PD. However, these differences were no longer significant after Bonferroni multiple comparisons correction highlighting the need for larger, longitudinal studies.

Recently approved and emerging drug options for migraine prophylaxis.

INTRODUCTION: Migraine occupies the first position regarding the disability caused in female working population (15-49 years). Research in the field of prophylaxis in this pathology has made enormous strides in recent years. AREAS COVERED: In this narrative review, we retrace the most important scientific evidence regarding recently approved and emerging drugs for the prophylactic treatment of migraine. The purpose of this article is in fact to evaluate currently approved or emerging pharmacological agents for migraine prophylaxis. This review is based on the literature published in the peer review journal obtained through PubMed, Cochrane library, Clinicaltrials.gov, and US FDA. EXPERT OPINION: Monoclonal antibodies (mAbs) that target the calcitonin gene-related peptide signaling pathway (CGRP) have marked an innovation in prophylactic migraine therapy. The combination of Onabotulinumtoxin-A (OBTA) and mAbs appears to be an effective, but costly, therapeutic option for resistant cases. New classes of molecules like gepants and ditans seem to give exceptional results. In addition, new prophylactic drugs are emerging with several targets: the pituitary adenylate cyclase-activating polypeptide (PACAP), ion channels, several receptors coupled to G proteins, orexin, and glutamate. All these therapies will implement and improve migraine management, as well as personalized medicine for each patient.

Localized electronic vacancy level and its effect on the properties of doped manganites.

Oxygen vacancies are common to most metal oxides and usually play a crucial role in determining the properties of the host material. In this work, we perform ab initio calculations to study the influence of vacancies in doped manganites [Formula: see text], varying both the vacancy concentration and the chemical composition within the ferromagnetic-metallic range ([Formula: see text]). We find that oxygen vacancies give rise to a localized electronic level and analyse the effects that the possible occupation of this defect state can have on the physical properties of the host. In particular, we observe a substantial reduction of the exchange energy that favors spin-flipped configurations (local antiferromagnetism), which correlate with the weakening of the double-exchange interaction, the deterioration of the metallicity, and the degradation of ferromagnetism in reduced samples. In agreement with previous studies, vacancies give rise to a lattice expansion when the defect level is unoccupied. However, our calculations suggest that under low Sr concentrations the defect level can be populated, which conversely results in a local reduction of the lattice parameter. Although the exact energy position of this defect level is sensitive to the details of the electronic interactions, we argue that it is not far from the Fermi energy for optimally doped manganites ([Formula: see text]), and thus its occupation could be tuned by controlling the number of available electrons, either with chemical doping or gating. Our results could have important implications for engineering the electronic properties of thin films in oxide compounds.

Constraining the Neutron Star Equation of State Using Multiband Independent Measurements of Radii and Tidal Deformabilities.

Using a Bayesian approach, we combine measurements of neutron star macroscopic observables obtained by astrophysical and gravitational observations to derive joint constraints on the equation of state (EOS) of matter at supranuclear density. In our analysis, we use two sets of data: (i) the masses and tidal deformabilities measured in the binary neutron star event GW170817, detected by LIGO and Virgo, and (ii) the masses and stellar radii measured from observations of nuclear bursts in accreting low-mass x-ray binaries. Using a phenomenological parametrization of the equation of state, we compute the posterior probability distributions of the EOS parameters, using which we infer the posterior distribution for the radius and the mass of the two neutron stars of GW170817. The constraints we set on the radii are tighter than previous bounds.

Probing Planckian Corrections at the Horizon Scale with LISA Binaries.

Several quantum-gravity models of compact objects predict microscopic or even Planckian corrections at the horizon scale. We explore the possibility of measuring two model-independent, smoking-gun effects of these corrections in the gravitational waveform of a compact binary, namely, the absence of tidal heating and the presence of tidal deformability. For events detectable by the future space-based interferometer LISA, we show that the effect of tidal heating dominates and allows one to constrain putative corrections down to the Planck scale. The measurement of the tidal Love numbers with LISA is more challenging but, in optimistic scenarios, it allows us to constrain the compactness of a supermassive exotic compact object down to the Planck scale. Our analysis suggests that highly spinning, supermassive binaries at 1-20 Gpc provide unparalleled tests of quantum-gravity effects at the horizon scale.

A Two-Dimensional Manganese Gallium Nitride Surface Structure Showing Ferromagnetism at Room Temperature.

Practical applications of semiconductor spintronic devices necessitate ferromagnetic behavior at or above room temperature. In this paper, we demonstrate a two-dimensional manganese gallium nitride surface structure (MnGaN-2D) which is atomically thin and shows ferromagnetic domain structure at room temperature as measured by spin-resolved scanning tunneling microscopy and spectroscopy. Application of small magnetic fields proves that the observed magnetic domains follow a hysteretic behavior. Two initially oppositely oriented MnGaN-2D domains are rotated into alignment with only 120 mT and remain mostly in alignment at remanence. The measurements are further supported by first-principles theoretical calculations which reveal highly spin-polarized and spin-split surface states with spin polarization of up to 95% for manganese local density of states.

The magnetic structure of ß-cobalt hydroxide and the effect of spin-orientation.

Synchrotron X-ray and neutron diffraction experiments at various temperatures, down to 3 K, along with ab initio calculations, are carried out to elucidate the magnetic order of layered ß-cobalt-hydroxide. This combination of techniques allows for the unambiguous assignment of the magnetic structure of this material. Our results confirm that below the Néel temperature high-spin cobalt centers are ferromagnetically coupled within a layer, and antiferromagnetically coupled across layers (magnetic propagation vector k = (0,0,½)), in agreement with the indirect interpretation based on magnetic susceptibility measurements. A paramagnetic/antiferromagnetic transition is observed at around 15 K. Moreover, the thermal expansion behavior along the c-lattice direction, perpendicular to the layers, shows an inflection slightly above this temperature, at around 30 K. The neutron diffraction patterns and the non-collinear DFT+U calculations indicate that the magnetization forms an angle of about 35° with the cobalt planes. In particular, for an isolated ferromagnetic layer, the electronic structure calculations reveal sharp cusps on the potential energy surface when the spins point parallel or perpendicular to the planes, suggesting that the ferromagnetic superexchange mechanism is strongly sensitive to the orientation of the magnetic moment.

Constraining Modified Theories of Gravity with Gravitational-Wave Stochastic Backgrounds.

The direct discovery of gravitational waves has finally opened a new observational window on our Universe, suggesting that the population of coalescing binary black holes is larger than previously expected. These sources produce an unresolved background of gravitational waves, potentially observable by ground-based interferometers. In this Letter we investigate how modified theories of gravity, modeled using the parametrized post-Einsteinian formalism, affect the expected signal, and analyze the detectability of the resulting stochastic background by current and future ground-based interferometers. We find the constraints that Advanced LIGO would be able to set on modified theories, showing that they may significantly improve the current bounds obtained from astrophysical observations of binary pulsars.

Transformation of spin information into large electrical signals using carbon nanotubes.

Spin electronics (spintronics) exploits the magnetic nature of electrons, and this principle is commercially applied in, for example, the spin valves of disk-drive read heads. There is currently widespread interest in developing new types of spintronic devices based on industrially relevant semiconductors, in which a spin-polarized current flows through a lateral channel between a spin-polarized source and drain. However, the transformation of spin information into large electrical signals is limited by spin relaxation, so that the magnetoresistive signals are below 1% (ref. 2). Here we report large magnetoresistance effects (61% at 5 K), which correspond to large output signals (65 mV), in devices where the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 microm gap between epitaxial electrodes of the highly spin polarized manganite La(0.7)Sr(0.3)MnO3. This spintronic system combines a number of favourable properties that enable this performance; the long spin lifetime in nanotubes due to the small spin-orbit coupling of carbon; the high Fermi velocity in nanotubes that limits the carrier dwell time; the high spin polarization in the manganite electrodes, which remains high right up to the manganite-nanotube interface; and the resistance of the interfacial barrier for spin injection. We support these conclusions regarding the interface using density functional theory calculations. The success of our experiments with such chemically and geometrically different materials should inspire new avenues in materials selection for future spintronics applications.

Distinct patterns of regeneration of central memory, effector memory and effector TCD8+ cell subsets after different hematopoietic cell transplant types: possible influence in the recovery of anti-cytomegalovirus immune response and risk for its reactivation.

TCD8+ cells may be divided into subsets with different phenotypes and functions: naive, central memory, effector memory and effector. Aiming to better understand the differences in early reconstitution of these TCD8+ cell subsets and their relationship with post-transplant anti-cytomegalovirus (CMV) immune responses recovery, we prospectively analyzed the transfer and expansion of these subsets in different transplant types. We found that graft cells from donor's peripheral blood, either allogeneic or autologous, were enriched for central memory, effector memory and effector phenotypes compared to allogeneic bone marrow grafts, as assessed by surface markers phenotyping and granzyme B expression. However, post-transplant, these subsets expanded in autologous recipients only, reaching numbers much greater than in allo-recipients at days +29 and +96. At the same time, autologous recipients presented less CMV reactivation and more vigorous CMV-induced interferon-gamma and lymphoproliferative responses. The marked loss of allo-transferred memory TCD8+ cells was probably due to the fact that they were more activated and more prone to apoptosis than auto-transferred TCD8+ cells as assessed by CD69 and active caspase 3 expression. Thus, transfer of peripheral blood stem cells in the allogeneic but not autologous setting is associated with poor expansion of memory TCD8+ cells, probably delaying antiviral immune reconstitution. These data may have important implications for the design of better strategies to immunoprotect this population against infectious challenges since different transplant types have different potentials for memory TCD8+ cells transfer and expansion.

Avaliação da reconstituição imunológica e da resposta anti-citomegalovirus nos receptores de transplante de medula óssea / Anti-cytomegalovirus immunity reconstitution following autologous and allogeneic stem cell and bone marrow transplantation as assessed by CD8+ T cell phenotyping and function

O citomegalovírus é uma séria ameaça aos receptores de transplante de medula óssea. A reativação está associada com uma imunidade mediada por células TCD8+ defeituosa. Nosso objetivo foi correlacionar as diferentes subpopulações de células TCD8+ com a reconstituição imunológica dos pacientes, especificamente a imunidade anti-citomegalovírus, analisando as subpopulações de células T infundidas nas diferentes modalidades de transplante de medula óssea. Receptores de transplante alogênico de células tronco mobilizadas para o sangue periférico (n=16) ou coletadas diretamente da medula óssea (n=28) e receptores de transplante autólogo de células tronco mobilizadas para o sangue periférico (n=22) foram avaliados. Nós mostramos que os receptores de células mobilizadas para o sangue periférico dos doadores, tanto nos transplantes alogênicos como nos autólogos, são proporcionalmente enriquecidos por fenótipos de células memória efetora e efetora, comparada aos receptores de células procedentes diretamente da medula óssea. Este maior número das subpopulações de células TCD8+ mais diferenciadas foi também correlacionado com maior número de células contendo altos níveis de granzima B, a qual é um outro marcador de valor dos linfócitos citotóxicos, sendo mais evidente nos receptores de transplante autólogo. Ao mesmo tempo, eles apresentaram menos freqüentemente reativação pelo citomegalovírus, e mais freqüentemente produziram interferon-gama em resposta ao antígeno do citomegalovírus / Cytomegalovirus is a serious threat to the recipients of bone marrow transplantation. Reactivation is associated with defective CD8+ T cell-mediated immunity. We aimed to correlate the different subsets of CD8+ T cells with the patients’ immune reconstitution, specifically anti CMV immunity, by analyzing the CD8+ T cell subsets infused in the different types of bone marrow transplantation. Recipients of allogeneic transplant of peripheral blood stem cells (n=16) or bone marrow (n=28) and recipients of autologous transplant of peripheral blood stem cells (n=22) were evaluated. We show that recipients of stem cells from donor’s peripheral blood, either allogeneic or autologous, are proportionally enriched for effector memory and effector phenotypes, compared to the recipients of stem cells of bone marrow origin...