ADAM10 as a biomarker for Alzheimer's disease: A systematic review.

BACKGROUND: Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-ß peptide (Aß), one of the pathological hallmarks of Alzheimer's disease (AD). OBJECTIVE: To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD. METHODS: A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: "Alzheimer" AND "ADAM10" AND "biomarker". Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239). RESULTS: Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection. CONCLUSION: Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.

Metas lipídicas: mundo real / Lipid goals: real world

INTRODUÇÃO: Frente à crescente evidência da redução de eventos cardiovasculares relacionados à redução do LDL colesterol (LDL-c), a Sociedade Brasileira de Cardiologia (SBC) propôs em 2017 metas mais agressivas de LDL-c. OBJETIVO: Avaliar em um centro terciário de cardiologia a proporção de pacientes que atingiram metas de LDL-c propostas pela Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose da SBC conforme estratificação de risco cardiovascular. METODOLOGIA: Foram analisados 2180 pacientes consecutivos em controle ambulatorial quanto à fatores de risco cardiovascular e terapia medicamentosa vigente. Conforme a diretriz, foram classificados em risco baixo, intermediário, alto e muito alto com metas de LDL-c < 130, 100, 70 e 50 mg/dL, respectivamente. RESULTADOS: A média de idade foi de 65 anos, sendo 53% dos pacientes do sexo feminino. Do total, 1225 (56.2%) eram de risco muito alto, 900 (41.3%) alto, 50 (2.3%) intermediário e 5 (0.2%) de baixo risco. Trezentos e noventa e nove pacientes (18.3%) atingiram as metas de LDL-c estabelecidas pela diretriz, sendo 11.1%, 26.2%, 46% e 80% de cada faixa de risco, respectivamente. Destes, 74.5% dos pacientes de muito alto risco, 56.2% de alto risco, 86% de risco intermediário e 40% de baixo risco estavam em uso de estatinas na intensidade e doses preconizadas pela diretriz. Apenas 148 (6.8%) pacientes não usavam estatina. (AU)

Estamos conseguindo atingir as metas atuais de LDL colesterol nos pacientes de muito alto risco cardiovascular? Quantos destes poderiam se beneficiar de inibidores da PCSK9 pelos critérios FOURIER/ODYSSEY e NICE? / Are we meeting current LDL cholesterol targets in patients at very high cardiovascular risk? How many of these could benefit from PCSK9 inhibitors by the FOURIER / ODYSSEY and NICE criteria?

INTRODUÇÃO: Com o aumento de evidências que a diminuição do LDL colesterol (LDL) se relaciona com a diminuição de eventos cardiovasculares, diretrizes de diferentes partes do mundo objetivam menores metas de LDL através da estratificação de risco cardiovascular. A inibição dá para proteína converta-se subtilisina/kexina tipo 9 (PCSK9) reduz os níveis de LDL em até 60%, com subsequente diminuição em desfechos cardiovasculares. OBJETIVO: Nossa meta foi avaliar em um centro terciário de cardiologia a proporção de pacientes de muito alto risco cardiovascular que atingiram a meta de LDL < 50mg/dL atualmente proposto pela diretriz da Sociedade Brasileira de Cardiologia. Adicionalmente, nós averiguamos o número de pacientes que estavam recebendo terapia adequada com estatinas e quantos destes poderiam se beneficiar de inibidores da PCSK9 pelos critérios FOURIER/ODYSSEY e pelas recomendações propostas pelo National Institute for Health and Excellence (NICE). METODOLOGIA: Foram rastreados 2180 pacientes consecutivos de março de 2018 a fevereiro de 2019 para fatores de risco cardiovascular, níveis de colesterol e terapia medicamentosa vigente. Em seguida, foram estratificados conforme o risco cardiovascular, sendo avaliada a adequação à terapia com estatinas recomendada. Em seguida, avaliamos quantos dos pacientes de muito alto risco, que estavam em uso de estatinas de alta intensidade, apresentavam níveis de LDL utilizados para inclusão nos estudos FOURIER/ODYSSEY (≥ 70mg/dL) e recomendados pelo NICE (≥ 140mg/dL) para a introdução de inibidores da PCSK9. RESULTADOS: Dos 2180 pacientes avaliados, 1125 (56.2%) pacientes eram de muito alto risco cardiovascular. Destes pacientes, 136 (11.1%) apresentavam LDL < 50mg/dL, estando 320 (26.1%) pacientes adicionais com LDL < 70mg/dL. Quando avaliado o tratamento com estatinas vigente, 913 (74.5%) pacientes estavam recebendo estatinas de alta intensidade. Destes, 617 (65.9%) teriam indicação de introdução de inibidores da PCSK9 pelos critérios FOURIER/ODYSSEY e 88 (9.4%) pelas recomendações do NICE. CONCLUSÕES: Com metas progressivamente menores de LDL, a busca por níveis ideais de LDL é um desafio para a prática clínica atual. Por mais que pacientes estejam recebendo a terapia recomendada com estatinas, permanece a dificuldade em atingir metas ideais, principalmente no grupo de pacientes de maior risco. Esses pacientes se beneficiariam da inibição da PCSK9, sendo o critério NICE, uma estratégia mais custo-efetiva, ainda aplicável em uma proporção substancial de pacientes. (AU)

Hemangioma cavernoso cardíaco: o relato de um tumor raro / Cardiac cavernous hemangioma: the report of a rare tumor

Os tumores cardíacos são raros e podem ser divididos em primários ou secundários de acordo com sua origem. O acometimento do coração por metástases de outros tumores é o cenário mais comum. Quanto aos tumores primários, em média 75% são benignos e 25% são malignos. A maioria dos pacientes é assintomática até o surgimento de alterações hemodinâmicas ou invasão de estruturas. As manifestações clínicas variam desde intolerância ao exercício, dispneia e dor torácica até síncope e morte súbita. A suspeita diagnóstica tem crescido graças aos avanços na ecocardiografia, mas o padrão ouro para a definição ainda é a biópsia. É importante destacar que os avanços tecnológicos em estudos tomográficos e de ressonância magnética têm contribuído para maior detalhamento das lesões e consequentemente para o diagnóstico diferencial. O tratamento pode ser conservador nos casos assintomáticos e descobertos incidentalmente ou cirúrgico nos casos sintomáticos. Este relato trata de uma paciente do sexo feminino, 53 anos, hipertensa, diabética e tabagista em investigação de dor torácica. Ela foi submetida inicialmente à cintilografia de perfusão miocárdica com dipiridamol que constatou hipocaptação em paredes anterior e septal. Diante disso, solicitou-se coronariografia, a qual evidenciou constrição no terço distal da artéria descendente anterior, associada à imagem radiopaca em topografia justa-cardíaca anterior, sugerindo compressão extrínseca. Um ecocardiograma transtorácico foi realizado e identificou imagem hiperecogênica de aspecto esponjoso e heterogêneo, bem delimitada e com halo hiperecóico, situando-se adjacente às paredes anterior e anterolateral do ventrículo esquerdo. O estudo com Doppler sugeriu fluxo em seu interior. A ressonância magnética do coração destacou câmaras cardíacas de dimensões preservadas, função biventricular dentro da normalidade, ausência de fibrose miocárdica e volumosa massa pericárdica. Após discussão do caso entre as equipes responsáveis e orientação da paciente sobre os resultados, indicou-se a ressecção da massa associada à biópsia. A paciente foi operada no dia 29 de janeiro de 2019, apresentando boa evolução pós-operatória e obteve alta da terapia intensiva no 2º dia pós-operatório em boas condições clínicas. O estudo de anatomia patológica da peça cirúrgica demonstrou Hemangioma Cavernoso Cardíaco. (AU)

A direct comparison of experimental methods to measure dimensions of synthetic nanoparticles.

Nanoparticles have properties that depend critically on their dimensions. There are a large number of methods that are commonly used to characterize these dimensions, but there is no clear consensus on which method is most appropriate for different types of nanoparticles. In this work four different characterization methods that are commonly applied to characterize the dimensions of nanoparticles either in solution or dried from solution are critically compared. Namely, transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), and dynamic light scattering (DLS) are compared with one another. The accuracy and precision of the four methods applied nanoparticles of different sizes composed of three different core materials, namely gold, silica, and polystyrene are determined. The suitability of the techniques to discriminate different populations of these nanoparticles in mixtures are also studied. The results indicate that in general, scanning electron microscopy is suitable for large nanoparticles (above 50 nm in diameter), while AFM and TEM can also give accurate results with smaller nanoparticles. DLS reveals details about the particles' solution dynamics, but is inappropriate for polydisperse samples, or mixtures of differently sized samples. SEM was also found to be more suitable to metallic particles, compared to oxide-based and polymeric nanoparticles. The conclusions drawn from the data in this paper can help nanoparticle researchers choose the most appropriate technique to characterize the dimensions of nanoparticle samples.

Boson Sampling with Single-Photon Fock States from a Bright Solid-State Source.

A boson-sampling device is a quantum machine expected to perform tasks intractable for a classical computer, yet requiring minimal nonclassical resources as compared to full-scale quantum computers. Photonic implementations to date employed sources based on inefficient processes that only simulate heralded single-photon statistics when strongly reducing emission probabilities. Boson sampling with only single-photon input has thus never been realized. Here, we report on a boson-sampling device operated with a bright solid-state source of single-photon Fock states with high photon-number purity: the emission from an efficient and deterministic quantum dot-micropillar system is demultiplexed into three partially indistinguishable single photons, with a single-photon purity 1-g^{(2)}(0) of 0.990±0.001, interfering in a linear optics network. Our demultiplexed source is between 1 and 2 orders of magnitude more efficient than current heralded multiphoton sources based on spontaneous parametric down-conversion, allowing us to complete the boson-sampling experiment faster than previous equivalent implementations.

Measuring Entanglement in a Photonic Embedding Quantum Simulator.

Measuring entanglement is a demanding task that usually requires full tomography of a quantum system, involving a number of observables that grows exponentially with the number of parties. Recently, it was suggested that adding a single ancillary qubit would allow for the efficient measurement of concurrence, and indeed any entanglement monotone associated with antilinear operations. Here, we report on the experimental implementation of such a device-an embedding quantum simulator-in photonics, encoding the entangling dynamics of a bipartite system into a tripartite one. We show that bipartite concurrence can be efficiently extracted from the measurement of merely two observables, instead of 15, without full tomographic information.

Entangling quantum-logic gate operated with an ultrabright semiconductor single-photon source.

We demonstrate the unambiguous entangling operation of a photonic quantum-logic gate driven by an ultrabright solid-state single-photon source. Indistinguishable single photons emitted by a single semiconductor quantum dot in a micropillar optical cavity are used as target and control qubits. For a source brightness of 0.56 photons per pulse, the measured truth table has an overlap with the ideal case of 68.4±0.5%, increasing to 73.0±1.6% for a source brightness of 0.17 photons per pulse. The gate is entangling: At a source brightness of 0.48, the Bell-state fidelity is above the entangling threshold of 50% and reaches 71.0±3.6% for a source brightness of 0.15.

Experimental distribution of entanglement with separable carriers.

The key requirement for quantum networking is the distribution of entanglement between nodes. Surprisingly, entanglement can be generated across a network without direct transfer-or communication-of entanglement. In contrast to information gain, which cannot exceed the communicated information, the entanglement gain is bounded by the communicated quantum discord, a more general measure of quantum correlation that includes but is not limited to entanglement. Here, we experimentally entangle two communicating parties sharing three initially separable photonic qubits by exchange of a carrier photon that is unentangled with either party at all times. We show that distributing entanglement with separable carriers is resilient to noise and in some cases becomes the only way of distributing entanglement through noisy environments.

Optimisation and validation of a quantitative and confirmatory method for residues of macrolide antibiotics and lincomycin in kidney by liquid chromatography coupled to mass spectrometry.

A solid phase extraction followed by a liquid chromatography (LC)-tandem mass spectrometry (MS/MS) detection method for the confirmatory analysis of lincomycin (LIN), clindamycin (CLI), tilmicosin (TIM), erythromycin (ERI) and tylosin (TYL) residues in kidney were optimised and validated for monitoring and controlling the use of these antibiotics in food producing-animals. The method optimisation was carried out by testing changes in the extraction buffer pH and in the ammonium/acetonitrile concentrations on SPE eluent solutions. The optimised extraction procedure involved the extraction of the analytes with a pH 8 phosphate buffer, clean-up on a reversed-phase mixed-cation exchange cartridge, followed by the elution of the analytes in a 98:2 acetonitrile/ammonia solution, concentration in air flow and re-dissolved with an 1:1 methanol/water solution. The analytes were detected in an LC-MS/MS system in electrospray positive ionisation mode. The validation was performed according to the European Commission Decision 2002/657/EC. Linearity was established for all analytes using the method of least weighted squares and CCα values ranged from 5.3% to 21.1% higher than the minimum residue limit (MRL) values. The addition levels varied from 0.5 to 1.50 MRL for all analytes, with recoveries exceeding 92.5%. The relative standard deviations (RSD%) in terms of repeatability (n = 54) and reproducibility (n = 108) for all analytes were less than 21.6% and 21.4%, respectively. The uncertainties were calculated by simplified methods using the calibration curve uncertainty and the intermediate precision to obtain the combined measurement uncertainty. The results of the validation process demonstrated that this method is suitable for the quantification and confirmation of antibiotic residues for the Brazilian Residue and Contaminant Control Plan (PNCR).

Occurrence of antimicrobial residues in Brazilian food animals in 2008 and 2009.

Brazil is one of the most important countries as a producer and exporter of cattle and poultry. In 2009 cattle accounted for 30% of the export market and 41.4% for poultry meat. The Brazilian National Residues and Contaminants Control Plan (PNCRC) follows the guidelines set by the Codex Alimentarius Commission and checks compliance maximum residue limits (MRLs) to ensure the quality of these commodities. Kidney samples (n = 2978) were analysed between January 2008 and December 2009. Fifteen antibiotics of the macrolide and aminoglycoside groups (clindamycin, eritromycin, lincomycin, tylmicosin, tylosin, amikacin, apramycin, dihydrostreptomycin, gentamycin, higromycin, kanamycin, neomycin, spectinomycin, streptomycin, tobramycin) were determined by a microbiological screening method (FAST) and confirmed/quantified using liquid chromatography (LC-MS/MS and UPLC-MS/MS). In 2008, 1459 samples were analysed by a screening test and liquid chromatography with only one sample (0.07%) exceeded Brazilian legislation limits (>MRL). In 2009, 1519 samples were analysed and none exceeding Brazilian legislation limits (>MRL). The slaughterhouses of 16 states were monitored during the year of 2008, and 18 states were monitored in 2009, being the major producing states most sampled by the PNCRC.

Optimisation and validation of a quantitative and confirmatory LC-MS method for multi-residue analyses of ß-lactam and tetracycline antibiotics in bovine muscle.

A multi-residue method for the determination of the ß-lactam antibiotics ampicillin, cefazolin, cloxacillin, dicloxacillin, nafcillin, oxacillin, penicillin G, penicillin V and the tetracyclines chlotetracycline, tetracycline and oxytetracycline was optimised and validated in bovine muscle. The method is based on the extraction of the residues from muscle using water/acetonitrile (2/8, v/v) with subsequent use of dispersive solid-phase C18 and hexane for purification. Extracts were analysed using ultra-performance liquid chromatography (UPLC-MS/MS) coupled with the mass spectrometer in positive electrospray ionisation mode (ESI+) for all analytes. The method was validated according to the requirements of European Commission Decision 2002/657/EC. The validation results were obtained within the MRL range of 0-1.5 of the MRL, with recoveries varying from 90% to 110% and CV < 20% (n = 54), except for cloxacillin, dicloxacillin and nafcillin. However, matrix interference was observed. The decision limit (CCα) ranged from 10% to 15% of the MRL. The uncertainty measurement was estimated based on both bottom-up and top-down strategies and the uncertainty values were found to be lower than 20% of the MRL. The method has a simple extraction procedure whereby analytes are separated with reasonable resolutions in a single 11-min chromatographic run. According to the validation results, this method is suitable for monitoring ß-lactams and tetracyclines according to National Program for Residue and Contaminant Control - Brazil (NPRC-Brazil) in bovine muscle.

Validation of a quantitative and confirmatory method for residue analysis of aminoglycoside antibiotics in poultry, bovine, equine and swine kidney through liquid chromatography-tandem mass spectrometry.

The use of aminoglycoside antibiotics in food animals is approved in Brazil. Accordingly, Brazilian food safety legislation sets maximum levels for these drugs in tissues from these animals in an effort to guarantee that food safety is not compromised. Aiming to monitor the levels of these drugs in tissues from food animals, the validation of a quantitative, confirmatory method for the detection of residues of 10 aminoglycosides antibiotics in poultry, swine, equine and bovine kidney, with extraction using a solid phase and detection and quantification by LC-MS/MS was performed. The procedure is an adaptation of the US Department of Agriculture, Food Safety and Inspection Service (USDA-FSIS) qualitative method, with the inclusion of additional clean-up and quantification at lower levels, which proved more efficient. Extraction was performed using a phosphate buffer containing trifluoroacetic acid followed by neutralization, purification on a cationic exchange SPE cartridge, with elution with methanol/acetic acid, evaporation, and dilution in ion-pair solvent. The method was validated according to the criteria and requirements of the European Commission Decision 2002/657/EC, showing selectivity with no matrix interference. Linearity was established for all analytes using the method of weighted minimum squares. CCα and CCß varied between 1036 and 12,293 µg kg(-1), and between 1073 and 14,588 µg kg(-1), respectively. The limits of quantification varied between 27 and 688 µg kg(-1). The values of recovery for all analytes in poultry kidney, fortified in the range of 500-1500 µg kg(-1), were higher than 90%, and the relative standard deviations were lower than 15%, except spectinomycin (21.8%). Uncertainty was estimated using a simplified methodology of 'bottom-up' and 'top-down' strategies. The results showed that this method is effective for the quantification and confirmation of aminoglycoside residues and could be used by the Brazilian programme of residue control.

Reducing multi-photon rates in pulsed down-conversion by temporal multiplexing.

We present a simple technique to reduce the emission rate of higher-order photon events from pulsed spontaneous parametric down-conversion. The technique uses extra-cavity control over a mode locked ultrafast laser to simultaneously increase repetition rate and reduce the energy of each pulse from the pump beam. We apply our scheme to a photonic quantum gate, showing improvements in the non-classical interference visibility for 2-photon and 4-photon experiments, and in the quantum-gate fidelity and entangled state production in the 2-photon case.

Efficient measurement of quantum dynamics via compressive sensing.

The resources required to characterize the dynamics of engineered quantum systems--such as quantum computers and quantum sensors--grow exponentially with system size. Here we adapt techniques from compressive sensing to exponentially reduce the experimental configurations required for quantum process tomography. Our method is applicable to processes that are nearly sparse in a certain basis and can be implemented using only single-body preparations and measurements. We perform efficient, high-fidelity estimation of process matrices of a photonic two-qubit logic gate. The database is obtained under various decoherence strengths. Our technique is both accurate and noise robust, thus removing a key roadblock to the development and scaling of quantum technologies.

Violation of the Leggett-Garg inequality with weak measurements of photons.

By weakly measuring the polarization of a photon between two strong polarization measurements, we experimentally investigate the correlation between the appearance of anomalous values in quantum weak measurements and the violation of realism and nonintrusiveness of measurements. A quantitative formulation of the latter concept is expressed in terms of a Leggett-Garg inequality for the outcomes of subsequent measurements of an individual quantum system. We experimentally violate the Leggett-Garg inequality for several measurement strengths. Furthermore, we experimentally demonstrate that there is a one-to-one correlation between achieving strange weak values and violating the Leggett-Garg inequality.

Towards quantum chemistry on a quantum computer.

Exact first-principles calculations of molecular properties are currently intractable because their computational cost grows exponentially with both the number of atoms and basis set size. A solution is to move to a radically different model of computing by building a quantum computer, which is a device that uses quantum systems themselves to store and process data. Here we report the application of the latest photonic quantum computer technology to calculate properties of the smallest molecular system: the hydrogen molecule in a minimal basis. We calculate the complete energy spectrum to 20 bits of precision and discuss how the technique can be expanded to solve large-scale chemical problems that lie beyond the reach of modern supercomputers. These results represent an early practical step toward a powerful tool with a broad range of quantum-chemical applications.

Experimental feedback control of quantum systems using weak measurements.

A goal of the emerging field of quantum control is to develop methods for quantum technologies to function robustly in the presence of noise. Central issues are the fundamental limitations on the available information about quantum systems and the disturbance they suffer in the process of measurement. In the context of a simple quantum control scenario-the stabilization of nonorthogonal states of a qubit against dephasing-we experimentally explore the use of weak measurements in feedback control. We find that, despite the intrinsic difficultly of implementing them, weak measurements allow us to control the qubit better in practice than is even theoretically possible without them. Our work shows that these more general quantum measurements can play an important role for feedback control of quantum systems.

Diet of the freshwater stingray Potamotrygon motoro (Chondrichthyes: Potamotrygonidae) on Marajó Island (Pará, Brazil).

The stomach contents of 137 examples of Potamotrygon motoro caught in 3 locations (Muaná, Afuá and Lake Arari) on Marajó Island were analysed. The values of the Index of Relative Importance (IRI) and its respective percentage (%IRI) were calculated. The level of repletion 1 (1/4 full) was the most representative for both sexes, as well as for immature and mature specimens. Most of the food items found were well-digested. The food items identification indicated the presence of 15 orders, including insects, mollusks, crustaceans, annelids and fish. Differences in diet were observed among the locations studied when comparing %IRI, crustaceans being the most preferred in Afuá, fish in Lake Arari and mollusks in Muaná.

Immunophenotypic aspects of cylindroma and nodular hidradenoma.

BACKGROUND: Some adnexal tumours have many controversies about their histogenesis. OBJECTIVES: To evaluate the eccrine and/or apocrine differentiation phenotype in cases of cylindroma and clear cell hidradenoma with CD15 and p63 antibodies. METHODOLOGY: Slides and blocks of six cases of cylindroma and seven cases of nodular hidradenoma (clear cells) were analyzed by the technique of immunohistochemistry with CD15 and p63 antibodies. RESULTS: In all cases of cylindroma we obtained negative results for CD15 antibody and positive for p63 antibody. In five of seven cases of nodular hidradenoma (clear cell), we could easily observe clear cells between 20% and 50% of tumour cells. In the two other cases, cystic lesions were present and occasional clear cells could be seen. The reaction with CD15 antibody was positive in granular and cytoplasmic pattern in six of seven cases, especially in cells with suggestive clear cytoplasm in lower proportion than this clear cells could be seen in haematoxylin and eosin. The positivity for p63 antibody, nuclear pattern, was observed in six of seven cases, in the major part of tumour cells. In only one case, the positivity was in 20% of cells. Limitation Samples are in small number because these are relatively rare tumours. CONCLUSIONS: The present study suggests eccrine origin for both tumours: cylindroma and clear cell hidradenoma.