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In recent years, emerging environmental pollutants have increasingly endangered the health of freshwater organisms. The gut microbiota exhibits sensitivity to medications, dietary factors and environmental pollutants, rendering it a novel target for toxicological studies. The gut microbiota can be a potential exposure route affecting the host's health. Herein, we review the current knowledge on two different but concurrent pollutants, microplastics and pesticides, regarding their impact on the gut microbiota, which includes alterations in microbial composition, gene expression, function, and health effects in the hosts. Moreover, synergetic interactions between microplastics and pesticides can exacerbate dysbiosis and health risks. We discuss health-related implications of gut microbial changes based on the consequences in metabolism, immunity, and physiology function. Further research is needed to discover the mechanisms underlying these effects and develop strategies for mitigating their harmful impacts on freshwater animals.
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Agua Dulce , Microbioma Gastrointestinal , Microplásticos , Plaguicidas , Contaminantes Químicos del Agua , Microbioma Gastrointestinal/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Microplásticos/toxicidad , Animales , Plaguicidas/toxicidadRESUMEN
RESUMEN Objetivo: Realizar una revisión de la literatura sobre el resultado de las sobredentaduras maxilares según el número de implantes dentales en pacientes edéntulos totales. Materiales y Métodos: Se realizó una búsqueda bibliográfica sistematizada en los motores de búsqueda Pubmed, Scopus y Web of Science y luego de establecer los criterios y filtros de la misma, se utilizaron 6 artículos. De los 6 artículos analizados, 4 fueron estudios de tipo ensayo clínico aleatorizado, 1 estudio prospectivo y 1 estudio retrospectivo. Resultados: Los resultados clínicos de las sobredentaduras maxilares, basados en el número de implantes sobre los cuales fueron soportadas, y comparando los protocolos más difundidos e investigados como los de All-on-4 y All-on-6, fueron similares. Se consideran óptimos, confiables, exitosos y longevos, sin diferencia significativa según el número de implantes dentales colocados. Conclusiones: Las sobredentaduras maxilares soportadas por 4 o 6 implantes fueron técnicas de tratamiento confiables, y ofrecen resultados comparables. Las complicaciones fueron limitadas y los resultados óptimos y duraderos.
ABSTRACT Objective: To review the literature on the outcome of maxillary overdentures according to the number of dental implants in edentulous patients. Materials and Methods: A systematic bibliographic search was carried out in the Pubmed, Scopus and Web of Science search engines and, after appliying the criteria and filters, 6 articles were used. Of the 6 articles analyzed, 4 were randomized clinical trial type studies, 1 prospective study and 1 retrospective study. Results: The results of maxillary overdentures, according to the number of implants used to support them, and comparing the most widespread and researched protocols such as All-on-4 and All-on-6, were similar. They are considered optimal, reliable, successful and long-lived, with no significant difference within the number of dental implants placed. Conclusions: Maxillary overdentures supported by 4 or 6 implants were reliable, and exhibit comparable results. The complications were limited, and the results were optimal and enduring.
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Humanos , Implantes Dentales , Boca Edéntula , Implantación DentalRESUMEN
Objetivo: Realizar una revisión de la literatura sobre el resultado de las sobredentaduras maxilares según el número de implantes dentales en pacientes edéntulos totales. Materiales y Métodos: Se realizó una búsqueda bibliográfica sistematizada en los motores de búsqueda Pubmed, Scopus y Web of Science y luego de establecer los criterios y filtros de la misma, se utilizaron 6 artículos. De los 6 artículos analizados, 4 fueron estudios de tipo ensayo clínico aleatorizado, 1 estudio prospectivo y 1 estudio retrospectivo. Resultados: Los resultados clínicos de las sobredentaduras maxilares, basados en el número de implantes sobre los cuales fueron soportadas, y comparando los protocolos más difundidos e investigados como los de All-on-4 y All-on-6, fueron similares. Se consideran óptimos, confiables, exitosos y longevos, sin diferencia significativa según el número de implantes dentales colocados. Conclusiones: Las sobredentaduras maxilares soportadas por 4 o 6 implantes fueron técnicas de tratamiento confiables, y ofrecen resultados comparables. Las complicaciones fueron limitadas y los resultados óptimos y duraderos.
Objective: To review the literature on the outcome of maxillary overdentures according to the number of dental implants in edentulous patients. Materials and Methods: A systematic bibliographic search was carried out in the Pubmed, Scopus and Web of Science search engines and, after appliying the criteria and filters, 6 articles were used. Of the 6 articles analyzed, 4 were randomized clinical trial type studies, 1 prospective study and 1 retrospective study. Results: The results of maxillary overdentures, according to the number of implants used to support them, and comparing the most widespread and researched protocols such as All-on-4 and All-on-6, were similar. They are considered optimal, reliable, successful and long-lived, with no significant difference within the number of dental implants placed. Conclusions: Maxillary overdentures supported by 4 or 6 implants were reliable, and exhibit comparable results. The complications were limited, and the results were optimal and enduring.
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MedicinaRESUMEN
As the number of Internet users grows, the increase in smart devices interconnected through the Internet of Things (IoT) have contributed to improvements in the functionality of everyday products and enhancement of user experience. Yet, they affect user privacy and render personal data more vulnerable. To foster a digital future fully aware of user privacy requirements, a line of design research emerges that focuses on balancing product innovation with user data protection. This matter relates to sociocultural, economic, and technological aspects, and its core is a human-centered design strategy. Still, there is a gap in academic research oriented towards guiding product developers on how to consider personal data privacy concerns when designing honest IoT devices. To define this gap and delve deeper into this relevant topic, this paper presents a systematic literature review of recent academic research using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. This review focuses on prevalent research topics such as data privacy, personal data, data surveillance, and user behaviour in IoT. The result is a state-of-the-art compilation of 45 scientific studies mapping the most relevant concepts and approaches for product development in the last ten years of research, aligned with some central research questions. The Discussion and Conclusion sections provide a deep understanding of the complexity of the fast-changing landscape of privacy and personal data management using IoT products. Finally, this study proposes future academic research directions devoted to providing product designer specific, specialised help from different (yet interconnected) scientific approaches.
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Currently, there are saturated frequency bands that affect the quality of service for new users. Cognitive radio provides an alternative solution to this problem through dynamic spectrum access. However, the solutions proposed in the current literature are focused on a centralized network and do not allow demonstrating the behavior in a multi-user environment, much less the effect that cooperation between secondary users can have. This article establishes a decision-making model for the best spectral opportunity selection with a cooperative approach in decentralized cognitive radio networks and contrasts its results with three multi-criteria decision-making algorithms: SAW, TOPSIS, and VIKOR. So, this research suggests a cooperative decision-making model based on four main modules. (1) a collaborative module for the exchange of information between SU; (2) a module for PU characterization; (3) a module of the probability of SU arrival; and (4) the SO feedback selection module. The results are obtained through simulations fed with experimental spectral occupancy data captured in a measurement campaign. Handoff and throughput were used as evaluation metrics, along with five levels of collaboration: 10%, 20%, 50%, 80%, and 100%, and eight different scenarios based on the type of network: GSM and Wi-Fi, the application type: real-time and best-effort, and the level of traffic: high and low. The contribution of this study lies in the fact that no current work includes the following relevant aspects for an adequate validation and evaluation of this proposal: First, the consideration of a decentralized cognitive radio network; second, the decision-making with cooperative strategies; third, different techniques for SO selection; fourth, the validation and evaluation with experimental spectral occupancy data captured in measurement campaigns; finally, the performance analysis in diverse networks, traffic levels, and types of applications.
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In this paper we discuss the details, limitations, and difficulties of the implementation in hardware of a memristor-based random number generator that exhibits monofractal/multifractal behavior. To do so, the components and selection criteria of a reference memristor and one proposed by the authors, the chaotic circuit leveraging them, and the processing that is performed on the chaotic signals to achieve the random discrete sequences are described. After applying the estimation tools, findings indicate that more than 60% of the proposed combinations allow generating random discrete sequences, with long-range dependence, and that both monofractal and multifractal behaviors can also be obtained. Consequently, a hardware system was achieved that can be used as a source of entropy in future synthetic biological signal generators.
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Ceratozamia morettii, C. brevifrons, and C. tenuis are cycads considered endangered in montane forests in the center of Veracruz state. However, the amount of theoretical and empirical information available on the historical distribution of these species and how they could be affected in the future by the effects of climate change still needs to be increased. Our objective was to generate information on the spatial distribution of the species since the last glacial maximum, present, and future. To map the spatial distribution of species, we created a potential distribution model for each species. The spatial data used for the models included 19 bioclimatic data variables in the present, at the last glacial maximum using two models (CCSM4 and MIROC), and in the future (2080) using two models of the RCP 8.5 scenario of climate change (HadGEM2-CC and MIROC5). We found that each species occupies a unique ecoregion and climatic niche. Ceratozamia morettii and C. tenuis have a similar pattern with an expansion of their distribution area since the last glacial maximum with a larger distribution area in the present and a projected reduction in their distribution under future climatic conditions. For C. brevifrons, we also showed an increase in their distributional area since the last glacial maximum. We also showed that this expansion will continue under future climatic conditions when the species reaches its maximum distributional area. Projections about the future of these endemic cycad species show changes in their habitat, highlighting that temperate zone species (C. morettii and C. tenuis) will face imminent extinction if no effort is made to protect them. On the other hand, the tropical climate species (C. brevifrons) will be favored.
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Zamiaceae , Ecosistema , Bosques , México , Cambio ClimáticoRESUMEN
OBJETIVO: Examinar las características sociodemográficas e indicadores de salud asociados con el cumplimiento de las recomendaciones de los comportamientos del movimiento en adultos mexicanos. Material y métodos. Estudio transversal que utilizó datos de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2022. Se obtuvo información de actividad física (AF), sedentarismo y sueño, características sociodemográficas e indicadores de salud en adultos de 20-78 años. Para el análisis se utilizaron regresiones logísticas y lineales ajustadas y no por covariables. RESULTADOS: Los adultos que viven en áreas urbanas tuvieron mayor posibilidad de no cumplir las recomendaciones de actividad física, sedentarismo, sueño y los comportamientos del movimiento (CM) en conjunto. No cumplir las recomendaciones de los tres CM se asoció con mayores niveles de glucosa, colesterol y tensión arterial elevada. Conclusión. La asociación de los CM con indicadores de salud muestra la importancia de identificar estrategias para promover estos comportamientos en la población mexicana.
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OBJETIVO: Describir la prevalencia de los comportamientos del movimiento (CM) en 24 horas en población mexicana. Material y métodos. Se recolectó información de actividad física (AF), tiempo sedentario y sueño para individuos de 10 a 78 años por medio de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). RESULTADOS: Más de 65% de niños y niñas no cumple con las recomendaciones de AF y pasan >2 horas/día frente a pantallas. Casi 91% de los adolescentes pasan >2 horas/día frente a pantalla. Más de 30% de los adolescentes y adultos no cumple con las recomendaciones de sueño. Sólo 1.5% de niños y niñas, 4.7% de adolescentes, 4.0% de los adultos y 1.5% de adultos mayores cumplieron las recomendaciones de los tres CM. Conclusión. Se evidencia la necesidad de desarrollar estrategias para contrarrestar la inactividad física, el comportamiento sedentario y el sueño insuficiente desde temprana edad hasta la adultez en población mexicana.
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The membrane potential of a cell (Vm) regulates several physiological processes. The voltage sensor domain (VSD) is a region that confers voltage sensitivity to different types of transmembrane proteins such as the following: voltage-gated ion channels, the voltage-sensing phosphatase (Ci-VSP), and the sperm-specific Na+/H+ exchanger (sNHE). VSDs contain four transmembrane segments (S1-S4) and several positively charged amino acids in S4, which are essential for the voltage sensitivity of the protein. Generally, in response to changes of the Vm, the positive residues of S4 displace along the plasma membrane without generating ionic currents through this domain. However, some native (e.g., Hv1 channel) and mutants of VSDs produce ionic currents. These gating pore currents are usually observed in VSDs that lack one or more of the conserved positively charged amino acids in S4. The gating pore currents can also be induced by the isolation of a VSD from the rest of the protein domains. In this review, we summarize gating pore currents from all families of proteins with VSDs with classification into three cases: (1) pathological, (2) physiological, and (3) artificial currents. We reinforce the model in which the position of S4 that lacks the positively charged amino acid determines the voltage dependency of the gating pore current of all VSDs independent of protein families.
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Activación del Canal Iónico , Semen , Masculino , Humanos , Activación del Canal Iónico/fisiología , Dominios Proteicos , Potenciales de la Membrana , AminoácidosRESUMEN
Osteoclasts are specialized cells responsible for bone resorption, a highly energy-demanding process. Focus on osteoclast metabolism could be a key for the treatment of osteolytic diseases including osteoporosis. In this context, AMP-activated protein kinase α1 (AMPKα1), an energy sensor highly expressed in osteoclasts, participates in the metabolic reconfiguration during osteoclast differentiation and activation. This study aimed to elucidate the role of AMPKα1 during osteoclastogenesis in vitro and its impact in bone loss in vivo. Using LysMcre/0AMPKâº1f/f animals and LysMcre/0 as control, we evaluated how AMPKα1 interferes with osteoclastogenesis and bone resorption activity in vitro. We found that AMPKα1 is highly expressed in the early stages of osteoclastogenesis. Genetic deletion of AMPKα1 leads to increased gene expression of osteoclast differentiation and fusion markers. In addition, LysMcre/0AMPKâº1f/f mice had an increased number and size of differentiated osteoclast. Accordingly, AMPKα1 negatively regulates bone resorption in vitro, as evidenced by the area of bone resorption in LysMcre/0AMPKâº1f/f osteoclasts. Our data further demonstrated that AMPKα1 regulates mitochondrial fusion and fission markers upregulating Mfn2 and downregulating DRP1 (dynamics-related protein 1) and that Ctskcre/0AMPKâº1f/f osteoclasts lead to an increase in the number of mitochondria in AMPKâº1-deficient osteoclast. In our in vivo study, femurs from Ctskcre/0AMPKâº1f/f animals exhibited bone loss associated with the increased number of osteoclasts, and there was no difference between Sham and ovariectomized group. Our data suggest that AMPKα1 acts as a negative regulator of osteoclastogenesis, and the depletion of AMPKα1 in osteoclast leads to a bone loss state similar to that observed after ovariectomy.
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Resorción Ósea , Osteoclastos , Animales , Femenino , Ratones , Resorción Ósea/genética , Resorción Ósea/metabolismo , Diferenciación Celular , Ratones Endogámicos C57BL , Osteoclastos/metabolismo , Osteogénesis , Osteoporosis/genética , Osteoporosis/metabolismo , Ligando RANK/metabolismoRESUMEN
In this study, we captured cane toads (Rhinella marina) in four sites located in different regions affected by anthropogenic activities in Mexico. Subsequently we analyzed liver tissue for the presence of organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs) The levels of these POPs in the toads' livers ranged from 863.2 to 3109.6 ng/g of lipid weight across all sites. A multivariate statistical analysis highlighted two sites with the highest POPs levels, with the most polluted site displaying a high level of PCBs, suggesting influence of industrial activities. The second most polluted site displayed significant amounts of OCs, linking this location to agricultural activity. Additionally, we found pesticide metabolites and isomers that allowed us to distinguish past and recent exposure events. Our observations indicate that R. marina is suitable bioindicator of sites impacted by anthropogenic activities.
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The microbial community of the urinary tract (urinary microbiota or urobiota) has been associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. While urinary Escherichia coli strains associated with urinary tract infection (UTI) and their phages have been catalogued for the urobiome, bacterium-plasmid-phage interactions have yet to be explored. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Putative F plasmids were predicted in 47 of 67 urinary E. coli isolates, and most of these plasmids carried genes that encode toxin-antitoxin (TA) modules, antibiotic resistance, and/or virulence. Urinary E. coli plasmids, from urinary microbiota strains UMB0928 and UMB1284, were conjugated into E. coli K-12 strains. These transconjugants included genes for antibiotic resistance and virulence, and they decreased permissivity to coliphage infection by the laboratory phage P1vir and the urinary phages Greed and Lust. Plasmids in one transconjugant were maintained in E. coli K-12 for up to 10 days in the absence of antibiotic resistance selection; this included the maintenance of the antibiotic resistance phenotype and decreased permissivity to phage. Finally, we discuss how F plasmids present in urinary E. coli strains could play a role in coliphage dynamics and the maintenance of antibiotic resistance in urinary E. coli. IMPORTANCE The urinary tract contains a resident microbial community called the urinary microbiota or urobiota. Evidence exists that it is associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. Bacterium-plasmid-phage interactions have been studied primarily in laboratory settings and are yet to be thoroughly tested in complex communities. This is especially true of the urinary tract, where the bacterial genetic determinants of phage infection are not well understood. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Urinary E. coli plasmids, encoding antibiotic resistance and transferred by conjugation into naive laboratory E. coli K-12 strains, decreased permissivity to coliphage infection. We propose a model by which urinary plasmids present in urinary E. coli strains could help to decrease phage infection susceptibility and maintain the antibiotic resistance of urinary E. coli. This has consequences for phage therapy, which could inadvertently select for plasmids that encode antibiotic resistance.
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Bacteriófagos , Infecciones por Escherichia coli , Sistema Urinario , Humanos , Escherichia coli/genética , Plásmidos/genética , Colifagos/genética , Bacteriófagos/genética , Infecciones por Escherichia coli/microbiología , Bacterias/genética , AntibacterianosRESUMEN
Currently, managing a group of satellites or robot manipulators requires coordinating their motion and work in a cooperative way to complete complex tasks. The attitude motion coordination and synchronization problems are challenging since attitude motion evolves in non-Euclidean spaces. Moreover, the equation of motions of the rigid body are highly nonlinear. This paper studies the attitude synchronization problem of a group of fully actuated rigid bodies over a directed communication topology. To design the synchronization control law, we exploit the cascade structure of the rigid body's kinematic and dynamic models. First, we propose a kinematic control law that induces attitude synchronization. As a second step, an angular velocity-tracking control law is designed for the dynamic subsystem. We use the exponential coordinates of rotation to describe the body's attitude. Such coordinates are a natural and minimal parametrization of rotation matrices which almost describe every rotation on the Special Orthogonal group SO(3). We provide simulation results to show the performance of the proposed synchronization controller.
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Understanding the dynamics of complex systems defined in the sense of Caputo, such as fractional differences, is crucial for predicting their behavior and improving their functionality. In this paper, the emergence of chaos in complex dynamical networks with indirect coupling and discrete systems, both utilizing fractional order, is presented. The study employs indirect coupling to produce complex dynamics in the network, where the connection between the nodes occurs through intermediate fractional order nodes. The temporal series, phase planes, bifurcation diagrams, and Lyapunov exponent are considered to analyze the inherent dynamics of the network. Analyzing the spectral entropy of the chaotic series generated, the complexity of the network is quantified. As a final step, we demonstrate the feasibility of implementing the complex network. It is implemented on a field-programmable gate array (FPGA), which confirms its hardware realizability.
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In this paper, synchronization and encrypted communication transmissions of analog and digital messages in a deterministic small-world network (DSWN) are presented. In the first instance, we use a network with 3 coupled nodes in a nearest-neighbor (NN) topology, then the amount of nodes is increased until reaching a DSWN with 24 nodes. The synchronization and encrypted communication transmissions using a DSWN are presented experimentally by using Chua's chaotic circuit as node, in both analog and digital electronic implementations, where for the continuous version (CV) we use operational amplifiers (OA), and in the discretized version (DV) we use Euler's numerical algorithm implemented in an embedded system by using an Altera/Intel FPGA and external digital-to-analog converters.
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Small mammals are important hosts and/or reservoirs of Trypanosoma spp. This study aimed to verify the prevalence of Trypanosoma spp. in non-volant small mammals from the Brazilian Cerrado and to test the effects of T. lainsoni on the neutrophil/lymphocyte ratio (N/L) and body condition in rodent and marsupial populations. For this, we collected blood samples of 293 individuals captured in five forest fragments between 2019 and 2020. Blood was used to prepare the blood smears and packed on filter paper for DNA extraction. Generalized linear models were performed to test the effects of T. lainsoni on host health. The DNA was submitted to nested PCR targeting the Trypanosoma spp. 18S rRNA gene. From blood smears analyzed by microscopy, we obtained a positivity rate of 7.2% for Trypanosoma spp. About 31.1% of Gracilinanus agilis, Didelphis albiventris, and Rhipidomys macrurus samples were positive in nested PCR. From the obtained sequences, 83.3% were genetically identical to T. lainsoni and about 11% to T. cruzi TcI. In addition, we reported the infection of T. lainsoni in Hylaeamys megacephalus. We suggest that T. lainsoni does not influence the body condition and N/L ratio for either G. agilis or R. macrurus. Overall, our results expand the host list of T. lainsoni and demonstrate the infection of small mammals by T. cruzi TcI in peri-urban areas.
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Enfermedad de Chagas , Didelphis , Marsupiales , Trypanosoma , Animales , Brasil/epidemiología , Prevalencia , Mamíferos , Trypanosoma/genética , Enfermedad de Chagas/epidemiología , RoedoresRESUMEN
Purpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M). Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan-Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as -10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated. Results: A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of -4.9% (95% CI: -9.2%, -0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs. Conclusion: The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified.
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BACKGROUND: Asymptomatic visceral leishmaniasis (VL) infection is a risk for transfusion safety. Leukoreduction has been an alternative for the prevention of some blood-borne diseases, including VL. This study aimed to evaluate the role of leukoreduction of cellular blood components as a control measure for transfusional VL transmission. RESEARCH DESIGN AND METHODS: A total of 161 polytransfused patients with non-leukoreduced blood components (HNL), 95 polytransfused with leukoreduced blood components (LH), and 202 non-transfused (NT) from endemic regions for VL and with a similar epidemiological profile. The detection of antibodies against VL was performed by ELISA and the presence of the parasite was investigated by real-time PCR. Statistical significance was defined as p < .05. RESULTS: When comparing three groups, ELISA results were statistically significant (p = .0065). The residual analysis of ELISA showed statistically significant for the HNL group compared to the general group (p = .002; OR: 5.6; CI: 1.7-25.8), demonstrating that individuals who received non-leukoreduced transfusions are five times more likely to acquire Leishmania infantum infection than the general. DISCUSSION: Higher prevalence in the group with HNL and low prevalence in those who received LH, similar to NT patients, highlight the risk of transfusional VL transmission and reinforce the role of leukoreduction in its prevention.