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Controlling quantum materials with light is of fundamental and technological importance. By utilizing the strong coupling of light and matter in optical cavities1-3, recent studies were able to modify some of their most defining features4-6. Here we study the magneto-optical properties of a van der Waals magnet that supports strong coupling of photons and excitons even in the absence of external cavity mirrors. In this material-the layered magnetic semiconductor CrSBr-emergent light-matter hybrids called polaritons are shown to substantially increase the spectral bandwidth of correlations between the magnetic, electronic and optical properties, enabling largely tunable optical responses to applied magnetic fields and magnons. Our results highlight the importance of exciton-photon self-hybridization in van der Waals magnets and motivate novel directions for the manipulation of quantum material properties by strong light-matter coupling.
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Molecules are the building blocks of all of nature's functional components, serving as the machinery that captures, stores and releases energy or converts it into useful work. However, molecules interact with each other over extremely short distances, which hinders the spread of energy across molecular systems. Conversely, photons are inert, but they are fast and can traverse large distances very efficiently. Using optical resonators, these distinct entities can be mixed with each other, opening a path to new architectures that benefit from both the active nature of molecules and the long-range transport obtained by the coupling with light. In this Review, we present the physics underlying the enhancement of energy transfer and energy transport in molecular systems, and highlight the experimental and theoretical advances in this field over the past decade. Finally, we identify several key questions and theoretical challenges that remain to be resolved via future research.
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The manipulation of coupled quantum excitations is of fundamental importance in realizing novel photonic and optoelectronic devices. We use electroluminescence to probe plasmon-exciton coupling in hybrid structures consisting of a nanoscale plasmonic tunnel junction and few-layer two-dimensional transition-metal dichalcogenide transferred onto the junction. The resulting hybrid states act as a novel dielectric environment that affects the radiative recombination of hot carriers in the plasmonic nanostructure. We determine the plexcitonic spectrum from the electroluminescence and find Rabi splittings exceeding 50 meV in the strong coupling regime. Our experimental findings are supported by electromagnetic simulations that enable us to explore systematically and in detail the emergence of plexciton polaritons as well as the polarization characteristics of their far-field emission. Electroluminescence modulated by plexciton coupling provides potential applications for engineering compact photonic devices with tunable optical and electrical properties.
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Despite significant theoretical efforts devoted to studying the interaction between quantized light modes and matter, the so-called ultrastrong coupling regime still presents significant challenges for theoretical treatments and prevents the use of many common approximations. Here we demonstrate an approach that can describe the dynamics of hybrid quantum systems in any regime of interaction for an arbitrary electromagnetic (EM) environment. We extend a previous method developed for few-mode quantization of arbitrary systems to the case of ultrastrong light-matter coupling, and show that even such systems can be treated using a Lindblad master equation where decay operators act only on the photonic modes by ensuring that the effective spectral density of the EM environment is sufficiently suppressed at negative frequencies. We demonstrate the validity of our framework and show that it outperforms current state-of-the-art master equations for a simple model system, and then study a realistic nanoplasmonic setup where existing approaches cannot be applied.
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This study aimed to evaluate the effectiveness of oral amoxicillin/clavulanate (AMX-CL) for the prevention of bacteremia following dental extractions. The study group (AMX-CLG) comprised 40 adults requiring dental extractions under general anesthesia who were administered a prophylactic regimen of 1875/125 mg of AMX-CL orally 1-2 h prior to the surgery. Venous blood samples were collected from each patient at baseline and at 30 s and 15 min after dental extractions. Samples were inoculated into BACTEC Plus culture bottles and processed in the BACTEC 9240. Conventional microbiological techniques were used for subcultures and further identification of the isolated bacteria. The results for the AMX-CLG were compared with those of a control group (CG; no prophylaxis) and an amoxicillin group (AMXG; 2 g of amoxicillin orally), consisting of randomly selected patients from among those participating in two clinical trials that we have previously published. The prevalence of bacteremia in the CG, AMXG, and AMX-CLG was 97%, 50%, and 15%, respectively, at 30 s after completing the extractions, and 67%, 10%, and 4% at 15 min, respectively, after the last extraction. The prevalence of bacteremia in the AMXG and the AMX-CLG at 30 s and at 15 min after completing the extractions was significantly lower than that in the CG (p < 0.001 and p < 0.001, respectively; Fisher's exact test). The prevalence of bacteremia in the AMX-CLG at 30 s after completing the extractions was significantly lower than that in the AMXG (p < 0.001; Fisher's exact test). Based in the results of this preliminary study, oral AMX-CL could be an excellent option for preventing bacteremia secondary to dental procedures in patients at risk.
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Bacteriemia , Extração Dentária , Adulto , Humanos , Extração Dentária/efeitos adversos , Amoxicilina/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Bacteriemia/prevenção & controle , Bacteriemia/epidemiologia , Bactérias , Antibacterianos/uso terapêuticoRESUMO
We investigate the quantum-optical properties of the light emitted by a nanoparticle-on-mirror cavity filled with a single quantum emitter. Inspired by recent experiments, we model a dark-field setup and explore the photon statistics of the scattered light under grazing laser illumination. Exploiting analytical solutions to Maxwell's equations, we quantize the nanophotonic cavity fields and describe the formation of plasmon-exciton polaritons (or plexcitons) in the system. This way, we reveal that the rich plasmonic spectrum of the nanocavity offers unexplored mechanisms for nonclassical light generation that are more efficient than the resonant interaction between the emitter natural transition and the brightest optical mode. Specifically, we find three different sample configurations in which strongly antibunched light is produced. Finally, we illustrate the power of our approach by showing that the introduction of a second emitter in the platform can enhance photon correlations further.
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Since the first description of a commensal seminal microbiome using sequencing, less than a decade ago, interest in the composition of this microbiome and its relationship with fertility has been growing. Articles using next-generation sequencing techniques agree on the identification of the most abundant bacterial phyla. However, at the genus level, there is still no consensus on which bacteria are most abundant in human seminal plasma. This discrepancy may be due to methodological variability such as sample collection, bacterial DNA extraction methodology, which hypervariable regions of 16S rRNA gene have been amplified, or bioinformatic analysis. In the present work, seminal microbiota of 14 control samples and 42 samples of idiopathic infertile patients were characterized based on full-length sequencing of the 16S rRNA gene using MinION platform from Oxford Nanopore. These same samples had been analyzed previously using Illumina's MiSeq sequencing platform. Comparison between the results obtained with the two platforms has been used to analyze the impact of sequencing method on the study of the seminal microbiome's composition. Seminal microbiota observed with MinION were mainly composed of the phyla Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria, with the most abundant genera being Peptoniphilus, Finegoldia, Staphylococcus, Anaerococcus, Campylobacter, Prevotella, Streptococcus, Lactobacillus, Ezakiella and Enterococcus. This composition was similar to that found by the Illumina platform, since these 10 most abundant genera were also among the most abundant genera detected by the Nanopore platform. In both cases, the top 10 genera represented more than 70% of the classified reads. However, relative abundance of each bacterium did not correlate between these two platforms, with intraindividual variations of up to 50 percentage points in some cases. Results suggest that the effect of the sequencing platform on the characterization of seminal microbiota is not very large at the phylum level, with slightly variances in Firmicutes and Actinobacteria, but presents differences at the genus level. These differences could alter the composition and diversity of bacterial profiles or posterior analyses. This indicates the importance of conducting multi-platform studies to better characterize seminal microbioma.
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Actinobacteria , Microbiota , Humanos , RNA Ribossômico 16S/genética , Microbiota/genética , Bactérias/genética , Firmicutes/genética , Proteobactérias/genética , Actinobacteria/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Clostridiales/genéticaRESUMO
Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors' samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06-0.85]) and DRB1*13:03 (p = 6.8 × 103, OR = 7.56[1.64-51.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients.
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Hemofilia A , Humanos , Hemofilia A/genética , Genótipo , Haplótipos/genética , Alelos , Frequência do Gene , Sequenciamento de Nucleotídeos em Larga Escala , Sistema Imunitário , Predisposição Genética para DoençaRESUMO
INTRODUCTION: In several countries, molecular diagnosis of haemophilia A (HA) and B (HB) is hampered by a lack of resources for DNA analysis. The advent of next-generation sequencing (NGS) has enabled gene analysis at a reasonable cost. AIM: Describe a collaboration between Cuban and Spanish researchers to identify candidate variants and investigate the molecular epidemiology of 106 Cuban haemophilia patients using NGS. PATIENTS/METHODS: The molecular analysis protocol included well-established LR-PCR procedures to detect F8 inversions, NGS with a 30-gene panel to sequence F8 and F9, and multiplex ligation-dependent probe amplification to identify large structural variants. RESULTS: One-hundred and thirty-one candidate variants were identified along F8, F9, and VWF; 72 were unique and 28 (39%) had not been previously recorded. Putative variants were identified in 105/106 patients. Molecular characterization enabled confirmation and reclassification of: 90 HA (85%), 15 HB (14%), and one type 2N VWD (1%). Null variants leading to non-production of FVIII or FIX were common in severe HA (64%), moderate HA (74%), and severe HB (60%), whereas missense variants were frequent in mild HA (57%) and moderate or mild HB (83%). Additional variants in VWF were identified in 16 patients. CONCLUSION: This is the first description of the molecular epidemiology of HA and HB in Cuba. Variants identified in index cases will be of value for local implementation of familial studies and prenatal diagnosis using the molecular approaches available in Cuba. The results of this protocolled genetic study improved the accuracy of the clinical diagnosis and will facilitate management of these patients.
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Hemofilia A , Cuba/epidemiologia , Fator VIII/genética , Feminino , Hemofilia A/diagnóstico , Hemofilia A/epidemiologia , Hemofilia A/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Gravidez , TecnologiaRESUMO
Recently, two rich and exciting research fields, layered two-dimensional (2D) materials and metamaterials, have started overlapping. Metamaterials are artificial, engineered materials with broad metaphotonic prospects such as negative refraction, perfect lensing, subwavelength imaging, and cloaking. The possibility of achieving metaphotonic properties using metamaterials based on layered 2D materials has been extensively exploited. Because they are highly tunable and adjustable with the ease of micro- and nanofabrication, 2D materials exhibit diverse optical properties such as natural negative refraction, natural anisotropic behavior, and even hyperbolic dispersion. A combination of 2D materials with conventional metamaterials promises a variety of prospective applications. In this review, we illustrate how the concept of metamaterials and their associated metaphotonic capabilities are naturally born in 2D materials. The multifunctionality of 2D materials may enable the manufacture of novel optical devices that work in a broad frequency range, from visible to terahertz, with particularly low loss, high speed, gated tunability, and miniaturized sizes. This new area of research links the fields of photonics, optoelectronics, and plasmonics with that of metamaterials and may provide insights to future innovations for 2D-material-inspired metaphotonic devices.
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We develop a framework that provides a few-mode master equation description of the interaction between a single quantum emitter and an arbitrary electromagnetic environment. The field quantization requires only the fitting of the spectral density, obtained through classical electromagnetic simulations, to a model system involving a small number of lossy and interacting modes. We illustrate the power and validity of our approach by describing the population and electric field spatial dynamics in the spontaneous decay of an emitter placed in a complex hybrid plasmonic-photonic structure.
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INTRODUCTION: Type 2N von Willebrand disease (VWD) is characterized by a decreased affinity of von Willebrand factor (VWF) for factor VIII (FVIII). Abnormal binding of FVIII to VWF (VWF:FVIIIB), results in low FVIII plasma levels, which can lead to a misdiagnosis of mild haemophilia A. Accurate diagnosis of type 2N VWD is essential for appropriate genetic counselling and therapy. This disease can be distinguished from haemophilia A by in vitro assays (measurement VWF:FVIIIB activity) and/or genetic analysis. AIM: To identify the current challenges in the diagnosis and treatment of this type of VWD and provide an in-depth description of the phenotypes and mutations identified. RESULTS: Twenty-eight patients had at least one type 2N mutation, and 13 of these had a type 2N mutation combined with other variations. Three type 2N mutations were detected: p.Arg816Trp, p.Arg854Gln, and p.Arg763Ser. Two of these are the most frequently described mutations worldwide. This mutational spectrum differs from the broad spectrum seen in neighbouring France, where at least eight distinct 2N mutations have been found. In the PCM-EVW-ES cohort, 11 asymptomatic type 2N carriers with borderline FVIII plasma levels would probably have been excluded if the evaluation had been based on clinical and laboratory data only. Likewise, three patients with a severe phenotype would have been classified as homozygous for a 2N mutation if only the phenotype study had been performed. CONCLUSION: The high detection yield and affordability of next-generation sequencing support the use of this technology as a first-line diagnostic tool in this setting.
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Hemofilia A , Doença de von Willebrand Tipo 2 , Doenças de von Willebrand , Fator de von Willebrand/genética , Fator VIII/genética , Heterozigoto , Homozigoto , Humanos , Doença de von Willebrand Tipo 2/diagnóstico , Doença de von Willebrand Tipo 2/genéticaRESUMO
Radiative transfer of energy at the nanometre length scale is of great importance to a variety of technologies including heat-assisted magnetic recording, near-field thermophotovoltaics and lithography. Although experimental advances have enabled elucidation of near-field radiative heat transfer in gaps as small as 20-30 nanometres (refs 4-6), quantitative analysis in the extreme near field (less than 10 nanometres) has been greatly limited by experimental challenges. Moreover, the results of pioneering measurements differed from theoretical predictions by orders of magnitude. Here we use custom-fabricated scanning probes with embedded thermocouples, in conjunction with new microdevices capable of periodic temperature modulation, to measure radiative heat transfer down to gaps as small as two nanometres. For our experiments we deposited suitably chosen metal or dielectric layers on the scanning probes and microdevices, enabling direct study of extreme near-field radiation between silica-silica, silicon nitride-silicon nitride and gold-gold surfaces to reveal marked, gap-size-dependent enhancements of radiative heat transfer. Furthermore, our state-of-the-art calculations of radiative heat transfer, performed within the theoretical framework of fluctuational electrodynamics, are in excellent agreement with our experimental results, providing unambiguous evidence that confirms the validity of this theory for modelling radiative heat transfer in gaps as small as a few nanometres. This work lays the foundations required for the rational design of novel technologies that leverage nanoscale radiative heat transfer.
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AIMS: Research the association between health literacy (HL) and exclusive breastfeeding at 4-months postpartum. BACKGROUND: Despite the benefits of breastfeeding (BF), its rates are low worldwide. Among the reasons for abandonment is the level of maternal education. Maternal education has been associated with HL, but evidence between HL and BF maintenance is limited. DESIGN: A cross-sectional study. METHODS: The sample compromised 229 nursing mothers recruited from January 2018 to the end of December 2018 at Spain by systematic sampling method. Women were interviewed postpartum on parameters associated with the start and continuation of BF up to 4 months postpartum. Multivariate logistic regression models to explain exposure variables and exclusive BF cessation at 4 months. RESULTS: Approximately 10% of the participants had inadequate HL. Factors associated with early cessation of exclusive BF at 4 months in the multivariate model adjusted using a stepwise variable selection process based on a likelihood ratio test were civil status, risk of pregnancy, type of delivery, limited or inadequate level of HL, and LATCH score at discharge, with an 85.6% area under the ROC curve. CONCLUSIONS: Our study offers preliminary evidence regarding the hitherto inconsistent relation between HL and early cessation exclusive BF at 4 months, supporting the conduct of further studies with larger sample sizes and greater statistical power. Such studies are warranted before endorsing HL-based interventions aiming to mitigate early cessation exclusive BF. IMPACT: Low or inadequate HL is linked to multiple poor health and clinical outcomes. We investigated the prevalence of exclusive BF at 4 months postpartum, and the impact of HL in maintaining optimal exclusive BF practices. Limited or inadequate HL was one of the factors associated with early cessation of exclusive BF in the multivariate regression model, although further research is needed.
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Aleitamento Materno , Letramento em Saúde , Gestantes , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Mães , Gravidez , Gestantes/psicologia , EspanhaRESUMO
A single photon in a strongly nonlinear cavity is able to block the transmission of a second photon, thereby converting incident coherent light into antibunched light, which is known as the photon blockade effect. Photon antipairing, where only the entry of two photons is blocked and the emission of bunches of three or more photons is allowed, is based on an unconventional photon blockade mechanism due to destructive interference of two distinct excitation pathways. We propose quantum plexcitonic systems with moderate nonlinearity to generate both antibunched and antipaired photons. The proposed plexcitonic systems benefit from subwavelength field localizations that make quantum emitters spatially distinguishable, thus enabling a reconfigurable photon source between antibunched and antipaired states via tailoring the energy bands. For a realistic nanoprism plexcitonic system, chemical and optical schemes of reconfiguration are demonstrated. These results pave the way to realize reconfigurable nonclassical photon sources in a simple quantum plexcitonic platform.
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Readthrough therapy relies on the use of small molecules that enable premature termination codons in mRNA open reading frames to be misinterpreted by the translation machinery, thus allowing the generation of full-length, potentially functional proteins from mRNA carrying nonsense mutations. In patients with hemophilia A, nonsense mutations potentially sensitive to readthrough agents represent approximately 16% of the point mutations. The aim of this study was to measure the readthrough effect of different compounds and to analyze the influence of premature termination codon context in selected nonsense mutations causing hemophilia A. To this end, primary fibroblasts from three patients with hemophilia A caused by nonsense mutations (p.W1586X, p.Q1636X and p.R1960X) and Chinese hamster ovary (CHO) cells transfected with 12 different plasmids encoding mutated F8 (p.Q462X, p.Q1705X, p.Q1764X, p.W274X, p.W1726X, p.W2015X, p.W2131X, p.R1715X, p.R1822X, p.R1960X, p.R2071X and p.R2228X) were treated with gentamicin, geneticin, PTC124, RTC13 or RTC14. Responses were assessed by analyzing not only F8 mRNA expression and FVIII biosynthesis (FVIII antigen by ELISA, western blot and immunofluorescence) but also the FVIII activity (by chromogenic assay). In the patients' fibroblasts, readthrough agents neither stabilized F8 mRNA nor increased FVIII protein or activity to detectable levels. In CHO cells, only in five of the 12 F8 variants, readthrough treatment increased both FVIII antigen and activity levels, which was associated with a reduction in intracellular accumulation of truncated forms and an increase in full-length proteins. These results provide experimental evidence of genetic context dependence of nonsense suppression by readthrough agents and of factors predicting responsiveness.
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Códon sem Sentido , Hemofilia A , Animais , Células CHO , Cricetinae , Cricetulus , Hemofilia A/tratamento farmacológico , Hemofilia A/genética , Humanos , RNA Mensageiro/genéticaRESUMO
Excitation-emission matrix (EEM) fluorescence spectroscopy has been applied to characterize several urban and industrial wastewaters (effluents from different types of industries: brewery, winery, dairy, biscuit, tinned fish industry, slaughterhouse, pulp mill, textile dyeing and landfill leachates), searching for specific fluorescence fingerprints. Tryptophan protein-like peaks (T1 and T2) are the predominant fluorescence in urban and food industry wastewaters (brewery, winery, dairy/milk, biscuit and fish farm industries) but no special fingerprint has been found to discriminate among them. Protein-like fluorescence also dominates the spectra of meat/fish industries (effluents from a tinned fish industry and a slaughterhouse), but in this case tyrosine protein-like peaks (B1 and B2) also appear in the spectra in addition to tryptophan-like peaks. This fact might constitute a specific feature to differentiate these wastewaters from others, since the appearance of peaks B is quite uncommon in wastewaters. The textile dyeing effluent shows a characteristic triple humic-like fluorescence (peaks A, C1 and C2) that may represent a specific fingerprint for this kind of effluent. Leachates from medium-aged and old landfills might also show a specific fingerprint in their EEM spectra: the sole presence of the humic-like peak C with very high fluorescence intensity. This feature also allows differentiating them from young landfill leachates, which show predominance of protein-like peaks. The fluorescence index (FI) does not seem to be very appropriate to characterize wastewaters and its usefulness might be limited to the study of humic substances in natural waters, although further studies are needed on this topic. However, the humification index (HIX) and the biological index (BIX) do seem to be useful for studying wastewaters, since they have provided consistent results in the present work. This study shows the potential of EEM fluorescence to identify the origin of some industrial effluents, although more research is needed to check these preliminary results.
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Águas Residuárias , Poluentes Químicos da Água/análise , Fluorescência , Substâncias Húmicas/análise , Indústrias , Espectrometria de FluorescênciaRESUMO
HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by in vitro intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of env and gag genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r = -0.8; P = 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches.IMPORTANCE There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.
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Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Inflamação/imunologia , Leucócitos Mononucleares/imunologia , Replicação Viral , Adulto , Linfócitos T CD4-Positivos/virologia , Citocinas/metabolismo , Feminino , Infecções por HIV/virologia , Humanos , Inflamação/virologia , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga ViralRESUMO
Diagnosis of von Willebrand disease (VWD) depends on personal and family history of bleeding and confirmatory laboratory testing. Currently available phenotypic tests for VWD contain potential sources for error that may distort results. Despite an exponential growth of information about the von Willebrand factor gene (VWF), the role of molecular diagnosis in VWD is still controversial. Due to the complexity and high cost of conventional molecular analyses, some investigators have recommended limiting this approach to distinguish suspected type 2N VWD from hemophilia A, type 2B from platelet-type VWD, and the exploration of type 3 VWD. New genetic methodologies and approaches are becoming available, but there is still some reluctance for their implementation in VWD diagnosis. This article discusses the pros and cons of molecular testing in VWD considering the experience obtained through the multicenter project "Molecular and Clinical Profile of VWD in Spain (PCM-EVW-ES)."