Advances in Diagnostics and Drug Discovery against Resistant and Latent Tuberculosis Infection.

Latent tuberculosis infection (LTBI) represents a subclinical, asymptomatic mycobacterial state affecting approximately 25% of the global population. The substantial prevalence of LTBI, combined with the risk of progressing to active tuberculosis, underscores its central role in the increasing incidence of tuberculosis (TB). Accurate identification and timely treatment are vital to contain and reduce the spread of the disease, forming a critical component of the global strategy known as "End TB." This review aims to examine and highlight the most recent scientific evidence related to new diagnostic approaches and emerging therapeutic treatments for LTBI. While prevalent diagnostic methods include the tuberculin skin test (TST) and interferon gamma release assay (IGRA), WHO's approval of two specific IGRAs for Mycobacterium tuberculosis (MTB) marked a significant advancement. However, the need for a specific test with global application viability has propelled research into diagnostic tests based on molecular diagnostics, pulmonary immunity, epigenetics, metabolomics, and a current focus on next-generation MTB antigen-based skin test (TBST). It is within these emerging methods that the potential for accurate distinction between LTBI and active TB has been demonstrated. Therapeutically, in addition to traditional first-line therapies, anti-LTBI drugs, anti-resistant TB drugs, and innovative candidates in preclinical and clinical stages are being explored. Although the advancements are promising, it is crucial to recognize that further research and clinical evidence are needed to solidify the effectiveness and safety of these new approaches, in addition to ensuring access to new drugs and diagnostic methods across all health centers. The fight against TB is evolving with the development of more precise diagnostic tools that differentiate the various stages of the infection and with more effective and targeted treatments. Once consolidated, current advancements have the potential to transform the prevention and treatment landscape of TB, reinforcing the global mission to eradicate this disease.

RELAX and FIRMNESS: The Combination of Muscle Relaxation with Botulinum Toxin and Collagen Biostimulation with Calcium Hydroxyapatite for the Treatment of the Cervical Region.

Introduction: There are several therapeutic modalities for neck rejuvenation, especially calcium hydroxylapatite. Botulinum toxin, by relaxing the mm. platysma, also provides improvement in facial contour. Combination treatments for this region are usually recommended as they offer better results. Objective: This study evaluated the efficacy and safety of the joint dilution of both products (Relax and Firmness - RF), applied in the same device, based on the treatment in the topography of the platysma muscle, ie, starting from the lower third of the face and extending to the neck. Methods: Prospective, blinded, controlled study with 10 participants randomly assigned to RF and 5 in the control group (treated with CaHA only). Results were recorded through the Vectra platform and subjectively evaluated through the GAIS scale by participants and blinded evaluators. Objective analysis was performed using corneometry. Times evaluated: pre-treatment, 30 and 90 days. Considered statistically significant when p<0.1. Results: 100% of the RF group reported "excellent improvement" at D30 and 30% at D90. In the control group, 100% reported "very improved" at D30 and 20% rated "excellent improvement" at D90. A higher and earlier satisfaction rate was observed in the RF group. No difference in corneometry was found between the groups at D30. At D90, the control group had a mean increase of 0.24 versus 5.17 in the RF group (p-value=0.089*). When we analyzed the percentage variation from baseline, the control group was stable, while the RF showed a mean increase of 8.89% (p-value=0.062*). Discussion: We demonstrated the safety and effectiveness of the association of both products, diluted and applied together through microcannulas. Minimization of punctures, patient comfort, and technique based on the anatomy of the platysma muscle underlie the technique. High rates of early satisfaction due to botulinum toxin (Relaxation) and late satisfaction due to CaHA (Firmness).

Impact of multidrug resistance on the management of bacterial infections in cirrhosis.

Patients with cirrhosis have an increased risk of infection and differently from other complications, that over the years are improving in their outcomes, infections in cirrhotic patients are still a major cause of hospitalization and death (up to 50% in-hospital mortality). Infections by multidrug-resistant organisms (MDRO) have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact. About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years. MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution. An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects, such as the type of infection (spontaneous bacterial peritonitis, pneumonia, urinary tract infection and spontaneous bacteremia), bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition (community acquired, healthcare associated or nosocomial). Furthermore, regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology. Antibiotic treatment is the most effective measure to treat infections caused by MDRO. Therefore, optimizing antibiotic prescribing is critical to effectively treat these infections. Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality. On the other hand, the supply of new agents to treat these infections is very limited. Thus, specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.

Green nanotechnology for the development of nanoparticles based on alginate associated with essential and vegetable oils for application in fruits and seeds protection.

Aiming to highlight the valorization of the natural products and the green synthesis processes, this work describes the development of a nanoscale system based on the use of alginate to encapsulate a blend of oils (vegetable and essential oils), not previously reported, with antibacterial and antioxidant actions. The study shows the influence of the polymer and surfactant concentrations on the physicochemical properties of the nanoparticles. The formulations were characterized by DLS, zeta potential, efficiency of encapsulation and stability. In addition, the antioxidant and antimicrobial properties of the systems were evaluated using the DPPH method and disk diffusion assays, respectively. The shelf life was studied by coating fruits and seeds. The results showed that the nanostructured system was stable, the efficiency of encapsulation was high and the nanoparticles size range was about 200-400 nm. The coating of fruits and seeds showed that the system was capable of inhibiting the growth of microorganisms and delaying the fruit maturation, indicating its potential for prolonging the shelf-life of fresh food.

Measuring the impact of COVID-19 vaccination and immunity waning: A modelling study for Portugal.

Vaccination strategies to control COVID-19 have been ongoing worldwide since the end of 2020. Understanding their possible effect is key to prevent future disease spread. Using a modelling approach, this study intends to measure the impact of the COVID-19 Portuguese vaccination strategy on the effective reproduction number and explore three scenarios for vaccine effectiveness waning. Namely, the no-immunity-loss, 1-year and 3-years of immunity duration scenarios. We adapted an age-structured SEIR deterministic model and used Portuguese hospitalisation data for the model calibration. Results show that, although the Portuguese vaccination plan had a substantial impact in reducing overall transmission, it might not be sufficient to control disease spread. A significant vaccination coverage of those above 5 years old, a vaccine effectiveness against disease of at least 80% and softer non-pharmaceutical interventions (NPIs), such as mask usage and social distancing, would be necessary to control disease spread in the worst scenario considered. The immunity duration scenario of 1-year displays a resurgence of COVID-19 hospitalisations by the end of 2021, the same is observed in 3-year scenario although with a lower magnitude. The no-immunity-loss scenario presents a low increase in hospitalisations. In both the 1-year and 3-year scenarios, a vaccination boost of those above 65 years old would result in a 53% and 38% peak reduction of non-ICU hospitalisations, respectively. These results suggest that NPIs should not be fully phased-out but instead be combined with a fast booster vaccination strategy to reduce healthcare burden.

Resistin Modulates the Functional Activity of Colostral Macrophages from Mothers with Obesity and Diabetes.

BACKGROUND: Obesity and diabetes are major public health problems. Resistin is an adipokine that links the two diseases. There are few reports regarding colostrum cells and resistin from mothers with obesity and diabetes. Thus, this study aimed to determine the functional activity of macrophages present in the breast milk and colostrum of diabetic mothers with obesity and the effects of resistin on these cells. METHODS: The women were divided according to BMI and glycemic status into normal weight non-diabetic, obese non-diabetic, normal weight type 2 diabetic, or obese type 2 diabetic groups. ELISA determined the resistin in colostrum. The cell subsets and apoptosis were determined by flow cytometry and the functional activity of cells by fluorescence microscopy. RESULTS: The resistin levels were higher in the colostrum from diabetic mothers with obesity. The frequencies of CD14+ cells and cells expressing CD95+, independent of resistin treatment, were higher in the colostrum from diabetic mothers with obesity. The frequency of cells expressing CD14+CD95+ was higher in cells not treated with resistin in the colostrum from diabetic mothers with obesity. Apoptosis, irrespective of the presence of resistin, increased, whereas microbicidal activity decreased in cells from diabetic mothers with obesity. CONCLUSION: The data suggest that hyperglycemia associated with low-grade inflammation caused by obesity affects the percentage of cells expressing CD14+CD95+, death by apoptosis, and microbicidal indices; meanwhile, resistin restored the microbicidal activity of colostrum cells.

Effects of Modified Melatonin Release on Human Colostrum Neutrophils to Induce Death in the MCF-7 Cell Line.

Cancer is one of the diseases with the highest mortality rate today, with breast cancer being the second most common type among the Brazilian population. Due to its etiological complexity and inefficiency of treatments, studies have focused on new forms of treatment. Among these forms of treatment, hormonal therapy seems to be an excellent auxiliary mechanism in tumoricidal activity, and melatonin has great potential as a modulator of the immune system. Thus, the present study is aimed at evaluating the effect of the hormone melatonin on the coculture of colostrum polymorphonuclear cells and MCF-7 cancer cells and evaluates the effect of this hormone using a modified transport system. A feasibility analysis was performed by fluorescence microscopy at three cell incubation times, 2 hours, 24 hours, and 72 hours. The measurement of cytokines in the cell supernatant occurred in 24 hours, and the apoptosis assay was performed in 72 hours using flow cytometry. The results showed higher levels of cell viability in groups treated with melatonin and less viability in groups containing a coculture of polymorphonuclear cells and MCF-7 after 72 hours of incubation. Furthermore, the apoptosis and necrosis rates were higher in coculture polymorphonuclear and MCF-7 cells, especially in groups containing microemulsion as a modified release agent. These data suggest that melatonin, especially if associated with a modified release system, has immunomodulatory effects on human colostrum polymorphonuclear cells. These cells can play a crucial role in the resolution of the tumor through their mediation and inflammatory action.

Crosslinking and depletion determine spatial instabilities in cytoskeletal active matter.

Active gels made of cytoskeletal proteins are valuable materials with attractive non-equilibrium properties such as spatial self-organization and self-propulsion. At least four typical routes to spatial patterning have been reported to date in different types of cytoskeletal active gels: bending and buckling instabilities in extensile systems, and global and local contraction instabilities in contractile gels. Here we report the observation of these four instabilities in a single type of active gel and we show that they are controlled by two parameters: the concentrations of ATP and depletion agent. We demonstrate that as the ATP concentration decreases, the concentration of passive motors increases until the gel undergoes a gelation transition. At this point, buckling is selected against bending, while global contraction is favored over local ones. Our observations are coherent with a hydrodynamic model of a viscoelastic active gel where the filaments are crosslinked with a characteristic time that diverges as the ATP concentration decreases. Our work thus provides a unified view of spatial instabilities in cytoskeletal active matter.

Front speed and pattern selection of a propagating chemical front in an active fluid.

Spontaneous pattern formation in living systems is driven by reaction-diffusion chemistry and active mechanics. The feedback between chemical and mechanical forces is often essential to robust pattern formation, yet it remains poorly understood in general. In this analytical and numerical paper, we study an experimentally motivated minimal model of coupling between reaction-diffusion and active matter: a propagating front of an autocatalytic and stress-generating species. In the absence of activity, the front is described by the well-studied Kolmogorov, Petrovsky, and Piskunov equation. We find that front propagation is maintained even in active systems, with crucial differences: an extensile stress increases the front speed beyond a critical magnitude of the stress, while a contractile stress has no effect on the front speed but can generate a periodic instability in the high-concentration region behind the front. We expect our results to be useful in interpreting pattern formation in active systems with mechanochemical coupling in vivo and in vitro.

Long-Lasting and Responsive DNA/Enzyme-Based Programs in Serum-Supplemented Extracellular Media.

DNA molecular programs are emerging as promising pharmaceutical approaches due to their versatility for biomolecular sensing and actuation. However, the implementation of DNA programs has been mainly limited to serum-deprived in vitro assays due to the fast deterioration of the DNA reaction networks by the nucleases present in the serum. Here, we show that DNA/enzyme programs are functional in serum for 24 h but are later disrupted by nucleases that give rise to parasitic amplification. To overcome this, we implement three-letter code networks that suppress autocatalytic parasites while still conserving the functionality of DNA/enzyme programs for at least 3 days in the presence of 10% serum. In addition, we define a new buffer that further increases the biocompatibility and conserves responsiveness to changes in molecular composition across time. Finally, we demonstrate how serum-supplemented extracellular DNA molecular programs remain responsive to molecular inputs in the presence of living cells, having responses 6-fold faster than the cellular division rate, and are sustainable for at least three cellular divisions. This demonstrates the possibility of implementing in situ biomolecular characterization tools for serum-demanding in vitro models. We foresee that the coupling of chemical reactivity to our DNA programs by aptamers or oligonucleotide conjugations will allow the implementation of extracellular synthetic biology tools, which will offer new biomolecular pharmaceutical approaches and the emergence of complex and autonomous in vitro models.

Programmed mechano-chemical coupling in reaction-diffusion active matter.

Embryo morphogenesis involves a complex combination of self-organization mechanisms that generate a great diversity of patterns. However, classical in vitro patterning experiments explore only one self-organization mechanism at a time, thus missing coupling effects. Here, we conjugate two major out-of-equilibrium patterning mechanisms­reaction-diffusion and active matter­by integrating dissipative DNA/enzyme reaction networks within an active gel composed of cytoskeletal motors and filaments. We show that the strength of the flow generated by the active gel controls the mechano-chemical coupling between the two subsystems. This property was used to engineer a synthetic material where contractions trigger chemical reaction networks both in time and space, thus mimicking key aspects of the polarization mechanism observed in C. elegans oocytes. We anticipate that reaction-diffusion active matter will promote the investigation of mechano-chemical transduction and the design of new materials with life-like properties.

DNA-Controlled Spatiotemporal Patterning of a Cytoskeletal Active Gel.

Living cells move and change their shape because signaling chemical reactions modify the state of their cytoskeleton, an active gel that converts chemical energy into mechanical forces. To create life-like materials, it is thus key to engineer chemical pathways that drive active gels. Here we describe the preparation of DNA-responsive surfaces that control the activity of a cytoskeletal active gel composed of microtubules: A DNA signal triggers the release of molecular motors from the surface into the gel bulk, generating forces that structure the gel. Depending on the DNA sequence and concentration, the gel forms a periodic band pattern or contracts globally. Finally, we show that the structuration of the active gel can be spatially controlled in the presence of a gradient of DNA concentration. We anticipate that such DNA-controlled active matter will contribute to the development of life-like materials with self-shaping properties.

Evolution of Toll, Spatzle and MyD88 in insects: the problem of the Diptera bias.

BACKGROUND: Arthropoda, the most numerous and diverse metazoan phylum, has species in many habitats where they encounter various microorganisms and, as a result, mechanisms for pathogen recognition and elimination have evolved. The Toll pathway, involved in the innate immune system, was first described as part of the developmental pathway for dorsal-ventral differentiation in Drosophila. Its later discovery in vertebrates suggested that this system was extremely conserved. However, there is variation in presence/absence, copy number and sequence divergence in various genes along the pathway. As most studies have only focused on Diptera, for a comprehensive and accurate homology-based approach it is important to understand gene function in a number of different species and, in a group as diverse as insects, the use of species belonging to different taxonomic groups is essential. RESULTS: We evaluated the diversity of Toll pathway gene families in 39 Arthropod genomes, encompassing 13 different Insect Orders. Through computational methods, we shed some light into the evolution and functional annotation of protein families involved in the Toll pathway innate immune response. Our data indicates that: 1) intracellular proteins of the Toll pathway show mostly species-specific expansions; 2) the different Toll subfamilies seem to have distinct evolutionary backgrounds; 3) patterns of gene expansion observed in the Toll phylogenetic tree indicate that homology based methods of functional inference might not be accurate for some subfamilies; 4) Spatzle subfamilies are highly divergent and also pose a problem for homology based inference; 5) Spatzle subfamilies should not be analyzed together in the same phylogenetic framework; 6) network analyses seem to be a good first step in inferring functional groups in these cases. We specifically show that understanding Drosophila's Toll functions might not indicate the same function in other species. CONCLUSIONS: Our results show the importance of using species representing the different orders to better understand insect gene content, origin and evolution. More specifically, in intracellular Toll pathway gene families the presence of orthologues has important implications for homology based functional inference. Also, the different evolutionary backgrounds of Toll gene subfamilies should be taken into consideration when functional studies are performed, especially for TOLL9, TOLL, TOLL2_7, and the new TOLL10 clade. The presence of Diptera specific clades or the ones lacking Diptera species show the importance of overcoming the Diptera bias when performing functional characterization of Toll pathways.

Comprehensive Quantitative Proteome Analysis of Aedes aegypti Identifies Proteins and Pathways Involved in Wolbachia pipientis and Zika Virus Interference Phenomenon.

Zika virus (ZIKV) is a global public health emergency due to its association with microcephaly, Guillain-Barré syndrome, neuropathy, and myelitis in children and adults. A total of 87 countries have had evidence of autochthonous mosquito-borne transmission of ZIKV, distributed across four continents, and no antivirus therapy or vaccines are available. Therefore, several strategies have been developed to target the main mosquito vector, Aedes aegypti, to reduce the burden of different arboviruses. Among such strategies, the use of the maternally-inherited endosymbiont Wolbachia pipientis has been applied successfully to reduce virus susceptibility and decrease transmission. However, the mechanisms by which Wolbachia orchestrate resistance to ZIKV infection remain to be elucidated. In this study, we apply isobaric labeling quantitative mass spectrometry (MS)-based proteomics to quantify proteins and identify pathways altered during ZIKV infection; Wolbachia infection; co-infection with Wolbachia/ZIKV in the A. aegypti heads and salivary glands. We show that Wolbachia regulates proteins involved in reactive oxygen species production, regulates humoral immune response, and antioxidant production. The reduction of ZIKV polyprotein in the presence of Wolbachia in mosquitoes was determined by MS and corroborates the idea that Wolbachia helps to block ZIKV infections in A. aegypti. The present study offers a rich resource of data that may help to elucidate mechanisms by which Wolbachia orchestrate resistance to ZIKV infection in A. aegypti, and represents a step further on the development of new targeted methods to detect and quantify ZIKV and Wolbachia directly in complex tissues.

Spatiotemporal Patterning of Living Cells with Extracellular DNA Programs.

Reactive extracellular media focus on engineering reaction networks outside the cell to control intracellular chemical composition across time and space. However, current implementations lack the feedback loops and out-of-equilibrium molecular dynamics for encoding spatiotemporal control. Here, we demonstrate that enzyme-DNA molecular programs combining these qualities are functional in an extracellular medium where human cells can grow. With this approach, we construct an internalization program that delivers fluorescent DNA inside living cells and remains functional for at least 48 h. Its nonequilibrium dynamics allows us to control both the time and position of cell internalization. In particular, a spatially inhomogeneous version of this program generates a tunable reaction-diffusion two-band pattern of cell internalization. This demonstrates that a synthetic extracellular program can provide temporal and positional information to living cells, emulating archetypal mechanisms observed during embryo development. We foresee that nonequilibrium reactive extracellular media could be advantageously applied to in vitro biomolecular tracking, tissue engineering, or smart bandages.

DNA-based long-lived reaction-diffusion patterning in a host hydrogel.

The development of living organisms is a source of inspiration for the creation of synthetic life-like materials. Embryo development is divided into three stages that are inextricably linked: patterning, differentiation and growth. During patterning, sustained out-of-equilibrium molecular programs interpret underlying molecular cues to create well-defined concentration profiles. Implementing this patterning stage in an autonomous synthetic material is a challenge that at least requires a programmable and long-lasting out-of-equilibrium chemistry compatible with a host material. Here, we show that DNA/enzyme reactions can create reaction-diffusion patterns that are extraordinarily long-lasting both in solution and inside an autonomous hydrogel. The life-time and stability of these patterns - here, traveling fronts and two-band patterns - are significantly increased by blocking parasitic side reactions and by dramatically reducing the diffusion coefficient of specific DNA strands. Immersed in oil, hydrogels pattern autonomously with limited evaporation, but can also exchange chemical information with other gels when brought into contact. Providing a certain degree of autonomy and being capable of interacting with each other, we believe these out-of-equilibrium hydrogels open the way for the rational design of primitive metabolic materials.

Tunable corrugated patterns in an active nematic sheet.

Active matter locally converts chemical energy into mechanical work and, for this reason, it provides new mechanisms of pattern formation. In particular, active nematic fluids made of protein motors and filaments are far-from-equilibrium systems that may exhibit spontaneous motion, leading to actively driven spatiotemporally chaotic states in 2 and 3 dimensions and coherent flows in 3 dimensions (3D). Although these dynamic flows reveal a characteristic length scale resulting from the interplay between active forcing and passive restoring forces, the observation of static and large-scale spatial patterns in active nematic fluids has remained elusive. In this work, we demonstrate that a 3D solution of kinesin motors and microtubule filaments spontaneously forms a 2D free-standing nematic active sheet that actively buckles out of plane into a centimeter-sized periodic corrugated sheet that is stable for several days at low activity. Importantly, the nematic orientational field does not display topological defects in the corrugated state and the wavelength and stability of the corrugations are controlled by the motor concentration, in agreement with a hydrodynamic theory. At higher activities these patterns are transient and chaotic flows are observed at longer times. Our results underline the importance of both passive and active forces in shaping active matter and demonstrate that a spontaneously flowing active fluid can be sculpted into a static material through an active mechanism.

Effects of the Q80K Polymorphism on the Physicochemical Properties of Hepatitis C Virus Subtype 1a NS3 Protease.

Hepatitis C virus genotype 1a (HCV-1a) comprises clades I and II. The Q80K polymorphism is found predominantly in clade I but rarely in clade II. Here, we investigated whether natural polymorphisms in HCV-1a clade II entailed structural protein changes when occurrence of the Q80K variant was simulated. Based on HCV-1a clade I and II protein sequences, the structure of the HCV-1a Q80K mutant NS3-4A was obtained by comparative modeling. Its physicochemical properties were studied by molecular dynamics simulations and network analysis. Results demonstrate that, in the presence of the K80 variant, clade II protease polymorphisms A91 and S/G174 led to variations in hydrogen bond occupancies. Structural analyses revealed differences in (i) flexibility of the H57 catalytic residue on the NS3 protease and (ii) correlations between amino acids on the NS3 protease and the NS4A cofactor. The latter indicated possible destabilization of interactions, resulting in increased separation of these proteins. The present findings describe how the relationships between different HCV-1a NS3 protease amino acid residues could affect the appearance of viral variants and the existence of distinct genetic barriers to HCV-1a isolates.

Optimization of magnetic resonance imaging protocol for the diagnosis of transient global amnesia.

OBJECTIVE: To emphasize the most appropriate magnetic resonance imaging (MRI) diffusion protocol for the detection of lesions that cause transient global amnesia, in order to perform an accurate examination, as well as to determine the ideal time point after the onset of symptoms to perform the examination. MATERIALS AND METHODS: We evaluated five patients with a diagnosis of transient global amnesia treated between 2012 and 2015. We analyzed demographic characteristics, clinical data, symptom onset, diffusion techniques, and radiological findings. Examination techniques included a standard diffusion sequence (b value = 1000 s/mm2; slice thickness = 5 mm) and a optimized diffusion sequence (b value = 2000 s/mm2; slice thickness = 3 mm). RESULTS: Brain MRI was performed at 24 h or 36 h after symptom onset, except in one patient, in whom it was performed at 12 h after (at which point no changes were seen) and repeated at 36 h after symptom onset (at which point it showed alterations in the right hippocampus). The standard and optimized diffusion sequences were both able to demonstrate focal changes in the hippocampi in all of the patients but one, in whom the changes were demonstrated only in the optimized sequence. CONCLUSION: MRI can confirm a clinical hypothesis of transient global amnesia. Knowledge of the optimal diffusion parameters and the ideal timing of diffusion-weighted imaging (> 24 h after symptom onset) are essential to improving diagnostic efficiency.

OBJETIVO: Enfatizar o protocolo de difusão mais adequado para detecção de lesões da amnésia global transitória, a fim de realizar um exame preciso, em tempo ideal, após o início dos sintomas. MATERIAIS E MÉTODOS: Foram analisados cinco pacientes com diagnóstico de amnésia global transitória atendidos entre 2012 e 2015, considerando-se dados demográficos, clínicos, tempo do início dos sintomas, técnicas de difusão e achados radiológicos. As técnicas incluíram uma sequência de difusão padrão (b = 1000 s/mm2; espessura do corte = 5 mm) e uma sequência de difusão otimizada (b = 2000 s/mm2; espessura de corte = 3 mm). RESULTADOS: A ressonância magnética de encéfalo foi realizada após 24 ou 36 horas do início dos sintomas, exceto em um paciente, em que foi realizada após 12 horas (sem alterações) e repetida após 36 horas (mostrando alterações hipocampais). Em todos os pacientes foram demonstradas alterações focais na difusão no hipocampo em ambas as técnicas, exceto em um paciente, em que as alterações foram demonstradas apenas na sequência otimizada. CONCLUSÃO: A ressonância magnética é capaz de confirmar a hipótese clínica de amnésia global transitória. O conhecimento dos parâmetros ótimos da técnica de difusão e o melhor tempo para a detecção das alterações (> 24 horas) são essenciais para aprimorar a eficiência diagnóstica.

Optimization of magnetic resonance imaging protocol for the diagnosis of transient global amnesia / Otimização do protocolo de ressonância magnética para o diagnóstico por imagem da amnésia global transitória

Abstract Objective: To emphasize the most appropriate magnetic resonance imaging (MRI) diffusion protocol for the detection of lesions that cause transient global amnesia, in order to perform an accurate examination, as well as to determine the ideal time point after the onset of symptoms to perform the examination. Materials and Methods: We evaluated five patients with a diagnosis of transient global amnesia treated between 2012 and 2015. We analyzed demographic characteristics, clinical data, symptom onset, diffusion techniques, and radiological findings. Examination techniques included a standard diffusion sequence (b value = 1000 s/mm2; slice thickness = 5 mm) and a optimized diffusion sequence (b value = 2000 s/mm2; slice thickness = 3 mm). Results: Brain MRI was performed at 24 h or 36 h after symptom onset, except in one patient, in whom it was performed at 12 h after (at which point no changes were seen) and repeated at 36 h after symptom onset (at which point it showed alterations in the right hippocampus). The standard and optimized diffusion sequences were both able to demonstrate focal changes in the hippocampi in all of the patients but one, in whom the changes were demonstrated only in the optimized sequence. Conclusion: MRI can confirm a clinical hypothesis of transient global amnesia. Knowledge of the optimal diffusion parameters and the ideal timing of diffusion-weighted imaging (> 24 h after symptom onset) are essential to improving diagnostic efficiency.

Resumo Objetivo: Enfatizar o protocolo de difusão mais adequado para detecção de lesões da amnésia global transitória, a fim de realizar um exame preciso, em tempo ideal, após o início dos sintomas. Materiais e Métodos: Foram analisados cinco pacientes com diagnóstico de amnésia global transitória atendidos entre 2012 e 2015, considerando-se dados demográficos, clínicos, tempo do início dos sintomas, técnicas de difusão e achados radiológicos. As técnicas incluíram uma sequência de difusão padrão (b = 1000 s/mm2; espessura do corte = 5 mm) e uma sequência de difusão otimizada (b = 2000 s/mm2; espessura de corte = 3 mm). Resultados: A ressonância magnética de encéfalo foi realizada após 24 ou 36 horas do início dos sintomas, exceto em um paciente, em que foi realizada após 12 horas (sem alterações) e repetida após 36 horas (mostrando alterações hipocampais). Em todos os pacientes foram demonstradas alterações focais na difusão no hipocampo em ambas as técnicas, exceto em um paciente, em que as alterações foram demonstradas apenas na sequência otimizada. Conclusão: A ressonância magnética é capaz de confirmar a hipótese clínica de amnésia global transitória. O conhecimento dos parâmetros ótimos da técnica de difusão e o melhor tempo para a detecção das alterações (> 24 horas) são essenciais para aprimorar a eficiência diagnóstica.