Characterization and efficacy of Salmonella phage cocktail PHA46 in the control of Salmonella Newport and Typhimurium internalized into cherry tomatoes.

Non-typhoid Salmonella enterica causes salmonellosis illness, and this bacterium can contaminate food throughout the production chain, including those that are consumed as raw products. Salmonella enterica can adhere to and internalize into fresh produce such as cherry tomatoes. It has been reported that lytic bacteriophages (phages) can be used as a biocontrol agent in the agricultural field, being an alternative for the control of Salmonella in red meat, fish, lettuce, and cabbage. The aim of this study was to characterize the two phages present in the PHA46 cocktail to determine their morphology, genome, host range, and resistance to different temperatures and pHs values; and later evaluate their lytic activity to reduce the adherence to and internalization of Salmonella enterica serovars Newport and Typhimurium into cherry tomatoes. In addition, in this work, we also explored the effect of the PHA46 cocktail on the virulence of S. Newport-45 and S. Typhimurium SL1344, recovered from the interior of cherry tomatoes, on the lifespan of the animal model Caenorhabditis elegans. The nematode C. elegans, recently has been used to test the virulence of Salmonella and it is easy to maintain and work with in the laboratory. The results revealed that the morphology obtained by Transmission Electron Microscopy of two phages from the PHA46 cocktail correspond to a myovirus, the analyses of their genomes sequences did not report virulence or antimicrobial resistance genes. The PHA46 sample is specific for 33 different serovars from different Salmonella strains and shows stability at 7 °C and pH 6. Also, the PHA46 cocktail was effective in reducing the adherence of S. Newport-45 and S. Typhimurium SL1344 to cherry tomatoes, at an average of 0.9 log10, respectively. Regarding internalized bacteria, the reduction was at an average of 1.2 log10, of the serovars mentioned above. The lifespan experiments in C. elegans showed by itself, that the PHA46 cocktail was harmless to the nematode, and the virulence from both Salmonella strains grown in vitro is diminished in the presence of the PHA46 cocktail. In conclusion, these results showed that the PHA46 cocktail could be a good candidate to be used as a biocontrol agent against Salmonella enterica.

Microsclerotia from Metarhizium robertsii: Production, ultrastructural analysis, robustness, and insecticidal activity.

Microsclerotia (MS) are considered one of the most promising propagules for use as active ingredients in biopesticides due to their tolerance to abiotic factors and ability to produce infective conidia for the control of pests. Therefore, the objective of this research was to establish the conditions required to induce the formation of microsclerotia in Metarhizium robertsii Mt004 and to study its development process, tolerance to abiotic factors and insecticidal activity of MS-derived conidia. M. robertsii started to form hyphal aggregates after 2 days and looked more compact after 8 days. MS were mature and pigmented after 20 days. The final yield was 2.0 × 103 MS/mL and MS size varied between 356.9 and 1348.4 µm. Ultrastructure analysis revealed that mature MS contained only a few live cells embedded in an extracellular matrix. Mature MS were more tolerance to UV-B radiation, heat and storage trials than conidia from Solid State Fermentation. MS-derived conidia were as virulent as conidia against Diatraea saccharalis larvae. These results showed that MS are promising propagules for the development of more persistent and efficient biopesticides for harsh environmental conditions. Our findings provide a baseline for production and a better understanding of microsclerotia development in M. robertsii strains.

Detection of a Multiple Circulation Event of Dengue Virus 2 Strains in the Northern Region of Brazil.

Dengue virus serotype 2 (DENV-2) is responsible for dengue epidemics on a global scale and is associated with severe cases of the disease. This study conducted a phylogenetic investigation of DENV-2 isolates from 2017 to 2021 originating from the northern states of Brazil. A total of 32 samples from DENV-2 isolates were analyzed, including 12 from Acre, 19 from Roraima, and one from Tocantins. Only one lineage of the Asian-American genotype and one lineage of the cosmopolitan genotype were observed: Lineage 1, Asian-American genotype (connection to Puerto Rico); Lineage 5, cosmopolitan genotype (connection to Peru). Our results provide important data regarding the study of DENV genotypes and lineage distribution and open up possibilities for probable introduction and dissemination routes.

Incidence of major cardiovascular events at 1, 2, and 5 years and mortality in incident patients on peritoneal dialysis regarding their nutritional status by bioimpedanciometry: A multicenter study in Colombia.

BACKGROUND: The nutritional status of incident patients on peritoneal dialysis (PD) has been associated with survival outcomes. Bioimpedanciometry (BCM) enables to establish a nutritional diagnosis, the volume status, and correlates these findings with survival. METHODS: This study used a retrospective multicenter historical cohort. RESULTS: In this study, which included 420 incident patients on peritoneal dialysis with a 5-year follow-up, a cumulative incidence of major adverse cardiovascular events (MACE) of 28.8% was found, being higher in the diabetic population at 36.8%. In regard to the nutritional status in this population, it was found that approximately 44% had altered nutritional status; 34% were found to be in sarcopenia; 6.7% sarcopenic obesity; and 2.8% in obesity (p < 0.001). In the survival analysis, a lower probability of survival was found in patients with overhydration (OH) greater than 3 L (p < 0.001) and in patients with altered nutritional status due to sarcopenia, sarcopenic obesity, and obesity (p 0.016). According to survival in the subgroup of the diabetic population, a lower probability of survival was found in this group of patients (p: 0.011). The overall mortality of the study population was 18%, being higher in the first 2 years, with the most important causes of mortality being cardiovascular. Of the deceased population, 51% were diabetic patients (p: 0.012). CONCLUSION: In incident patients on peritoneal dialysis, sarcopenic obesity, sarcopenia, overhydration status determined by BCM, and having a diagnosis of diabetes are related to a lower probability of survival; MACE outcomes are more frequent in the diabetic population.

Actividades de superación profesional de médicos generales integrales sobre el uso racional de medicamentos / Professional training activities of comprehensive general doctors on the rational use of medications i: en

Introducción: El uso irracional de medicamentos se debe, entre otros elementos, a la falta de superación profesional; situación con mayor repercusión en la atención primaria de salud, donde generalmente laboran los médicos generales integrales. Objetivo: Caracterizar las actividades de superación profesional de médicos generales integrales sobre el uso racional de medicamentos. Métodos: Se realizó un estudio descriptivo y transversal de 269 médicos generales integrales que laboraban en los consultorios del médico de la familia o en los servicios de urgencia de las 17 áreas de salud del municipio de Santiago de Cuba en el período comprendido desde enero hasta julio de 2022, quienes fueron seleccionados mediante muestreo probabilístico por conglomerado bietápico. Se consideró como variable las actividades de superación profesional relacionadas con el uso racional de medicamentos, las cuales fueron valoradas a través de 5 indicadores. Resultados: La triangulación metodológica de los resultados evidenció que el nivel alcanzado en cuanto a la frecuencia de realización de dichas actividades fue bajo (índice de 1,18), al igual que lo obtenido en los indicadores analizados, excepto en el referido a la autopreparación que mostró un nivel medio. Conclusiones: Las actividades de superación profesional de los médicos generales integrales relacionadas con el uso racional de medicamentos en el municipio de Santiago de Cuba se caracterizaron por un nivel bajo de frecuencia de realización.

Introduction: Irrational use of medications is, among other elements, due to the lack of professional training; situation with more repercussion in primary health care, where comprehensive general doctors generally work. Objective: To characterize the professional training activities of comprehensive general doctors on the rational use of medications. Methods: A descriptive and cross-sectional study of 269 comprehensive general doctors who worked in the family doctor offices or in the emergency services of the 17 health areas of Santiago de Cuba municipality was carried out from January to July, 2022, who were selected by means of a probabilistic sampling by biphase conglomerate. The activities of professional training related to the rational use of medications were considered as variable, which were valued through 5 indicators. Results: The methodological triangulation of the results evidenced that the level reached as for the frequency of realization of this activities was low (index of 1.18), as well as what was obtained in the analyzed indicators, except the one referred to the self-preparation which showed a mean level. Conclusions: Professional training activities of comprehensive general doctors related to the rational use of medications in Santiago de Cuba municipality were characterized by a low level of realization frequency.

Análisis del programa de Farmacología Clínica en el plan de estudio E para la carrera de Medicina / Analysis of the program of Clinical Pharmacology in the E plan study for the Medicine career i: en

Introducción: En Cuba han existido varias concepciones sobre planes de estudio. La necesidad de revisar y proponer cambios que aseguren los niveles de calidad deseados en el proceso de formación integral de los futuros profesionales motivó a investigar los elementos teóricos y metodológicos que regulan y orientan el proceso de enseñanza-aprendizaje en la asignatura Farmacología Clínica. Objetivo: Analizar el programa de Farmacología Clínica del plan de estudio E para la carrera de Medicina desde un enfoque crítico y sistematizado. Métodos: Se realizó un estudio cualitativo del programa de estudio de la asignatura Farmacología Clínica según el plan E, vigente en la Universidad de Ciencias Médicas de Santiago de Cuba, durante el 2022, para lo cual se utilizaron los métodos de revisión documental, los documentos rectores del proceso docente en la educación superior y la metodología propuesta por algunos autores. Resultados: Varios temas enunciaban un número excesivo de objetivos específicos sin tener en cuenta el nivel de asimilación; la forma de organización de la enseñanza más utilizada fue la conferencia. En las evaluaciones frecuentes no se tuvo en cuenta el trabajo investigativo independiente; en tanto, la bibliografía básica correspondió a una edición del 2002. Conclusiones: El programa no requirió trasformaciones temáticas, pero desde el punto de vista didáctico deben modificarse componentes del proceso de enseñanza-aprendizaje y, además, se debe actualizar la bibliografía básica pertinente.

Introduction: In Cuba several conceptions have existed on the study plans. The necessity to revise and propose changes that assure the levels of quality wanted in the process of integral formation of the future professionals motivated to investigate the theoretical and methodological elements that regulate and guide the teaching-learning process in the Clinical Pharmacology subject. Objective: To analyze the program of Clinical Pharmacology of the E plan study for the medicine career, from a critical and systematized approach. Methods: A qualitative study of the study program in the Clinical Pharmacology subject was carried out according to the E plan, effective in the University of Medical Sciences in Santiago de Cuba, during 2022, for which the methods of documental review, the rector documents of the teaching process in higher education and the methodology proposed by some authors were used. Results: Several topics enunciated an excessive number of specific objectives without taking into account the level of assimilation; the form of organization most used in teaching was the conference. Independent investigative work was not taken into account in frequent evaluations; meanwhile, the basic bibliography corresponded to an edition from 2002. Conclusions: The program did not require of thematic transformations, but from the didactic point of view components of the teaching-learning process should be modified, besides updating the pertinent basic literature.

The antipsychotic olanzapine reduces memory deficits and neuronal abnormalities in a male rat model of Autism.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.

Emergence of a New Strain of DENV-2 in South America: Introduction of the Cosmopolitan Genotype through the Brazilian-Peruvian Border.

Dengue virus 2 (DENV-2) seriously contributes to dengue-related mortality. It includes five nonsylvatic genotypes, with cosmopolitan being the most widespread with a significant contribution to the total number of DENV-2 cases globally. In South America, the cosmopolitan genotype was first recorded in 2019 in Madre de Dios, Peru, and then in Goiás (Midwest Brazil) in November 2021. In this study, we tested 163 human serum samples from Acre (Northern Brazil) collected during a DENV outbreak between 2020 and 2021 for all DENV genotypes by RT-qPCR. Of the 163 samples, 139 were positive for DENV-2, and 5 were positive for DENV-1. Five DENV-2-positive samples from early 2021 were sequenced, and the sequences clustered with the three other DENV-2 cosmopolitan genotype sequences already recorded on the continent. These results create a geographical link, suggesting the possible route of introduction of the DENV-2 cosmopolitan genotype into Brazil through the border with Peru, from which it may have dispersed to Midwest Brazil.

The Importance of Entomo-Virological Investigation of Yellow Fever Virus to Strengthen Surveillance in Brazil.

The largest outbreak of sylvatic yellow fever virus (YFV) in eight decades was recorded in Brazil between 2016-2018. Besides human and NHP surveillance, the entomo-virological approach is considered as a complementary tool. For this study, a total of 2904 mosquitoes of the Aedes, Haemagogus and Sabethes genera were collected from six Brazilian states (Bahia, Goiás, Mato Grosso, Minas Gerais, Pará, and Tocantins) and grouped into 246 pools, which were tested for YFV using RT-qPCR. We detected 20 positive pools from Minas Gerais, 5 from Goiás, and 1 from Bahia, including 12 of Hg. janthinomys and 5 of Ae. albopictus. This is the first description of natural YFV infection in this species and warns of the likelihood of urban YFV re-emergence with Ae. albopictus as a potential bridge vector. Three YFV sequences from Hg. janthinomys from Goiás and one from Minas Gerais, as well as one from Ae. albopictus from Minas Gerais were clustered within the 2016-2018 outbreak clade, indicating YFV spread from Midwest and its infection in a main and likely novel bridging vector species. Entomo-virological surveillance is critical for YFV monitoring in Brazil, which could highlight the need to strengthen YFV surveillance, vaccination coverage, and vector control measures.

Novel Rodent Arterivirus Detected in the Brazilian Amazon.

As part of a continuous effort to investigate the viral communities associated with wild mammals at the human-animal interface in an Amazonian metropolitan region, this study describes the detection of a novel rodent-borne arterivirus. A sample containing pooled organs of Oecomys paricola was submitted to RNA sequencing, and four sequences taxonomically assigned as related to the Arteriviridae family were recovered, corresponding to an almost complete genome of nearly 13 kb summed. In the phylogenetic analysis with the standard domains used for taxa demarcation in the family, the tentatively named Oecomys arterivirus 1 (OAV-1) was placed within the clade of rodent- and porcine-associated viruses, corresponding to the Variarterivirinae subfamily. The divergence analysis, based on the same amino acid alignment, corroborated the hypothesis that the virus may represent a new genus within the subfamily. These findings contribute to the expansion of the current knowledge about the diversity, host and geographical range of the viral family. Arterivirids are non-human pathogens and are usually species-specific, but the susceptibility of cell lines derived from different organisms should be conducted to confirm these statements for this proposed new genus in an initial attempt to assess its spillover potential.

Isolation of Flaviviruses and Alphaviruses with Encephalitogenic Potential Diagnosed by Evandro Chagas Institute (Pará, Brazil) in the Period of 1954-2022: Six Decades of Discoveries.

Viruses with encephalitogenic potential can cause neurological conditions of clinical and epidemiological importance, such as Saint Louis encephalitis virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Dengue virus, Zika virus, Chikungunya virus, Mayaro virus and West Nile virus. The objective of the present study was to determine the number of arboviruses with neuroinvasive potential isolated in Brazil that corresponds to the collection of viral samples belonging to the Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute (SAARB/IEC) of the Laboratory Network of National Reference for Arbovirus Diagnosis from 1954 to 2022. In the analyzed period, a total of 1,347 arbovirus samples with encephalitogenic potential were isolated from mice; 5,065 human samples were isolated exclusively by cell culture; and 676 viruses were isolated from mosquitoes. The emergence of new arboviruses may be responsible for diseases still unknown to humans, making the Amazon region a hotspot for infectious diseases due to its fauna and flora species characteristics. The detection of circulating arboviruses with the potential to cause neuroinvasive diseases is constant, which justifies the continuation of active epidemiological surveillance work that offers adequate support to the public health system regarding the virological diagnosis of circulating arboviruses in Brazil.

Do Fungicides Affect Alkaloid Production in Catharanthus roseus (L.) G. Don. Seedlings?

The presence of endophytes in plants is undeniable, but how significant their involvement is in the host plant biosynthetic pathways is still unclear. The results reported from fungicide treatments in plants varied. Fungicide treatment in Taxus was found to decrease the taxol content. In Ipomoea asarifolia, Pronto Plus and Folicur treatments coincided with the disappearance of ergot alkaloids from the plant. In Narcissus pseudonarcissus cv. Carlton, a mixture of fungicide applications decreased the alkaloids concentration and altered the carbohydrate metabolism. Jacobaea plants treated with Folicur reduced the pyrrolizidine alkaloids content. There have not been any studies into the involvement of endophytic fungi on alkaloids production of Catharanthus roseus until now. Though there is a report on the isolation of the endophytic fungi, Fusarium oxysporum from C. roseus, which was reported to produce vinblastine and vincristine in vitro. To detect possible collaborations between these two different organisms, fungicides were applied to suppress the endophytic fungi in seedlings and then measure the metabolomes by 1HNMR and HPLC analysis. The results indicate that endophytic fungi were not directly involved in alkaloids biosynthesis. Treatment with fungicides influenced both the primary and secondary metabolism of C. roseus. The systemic fungicides Pronto Plus and Folicur caused an increase in loganin and secologanin levels. In contrast, control samples had higher level of catharanthine and vindoline. This means that fungicide treatments cause changes in plant secondary metabolism.

Cellular mechanisms in brain aging: Focus on physiological and pathological aging.

Aging is a natural phenomenon characterized by accumulation of cellular damage and debris. Oxidative stress, cellular senescence, sustained inflammation, and DNA damage are the main cellular processes characteristic of aging associated with morphological and functional decline. These effects tend to be more pronounced in tissues with high metabolic rates such as the brain, mainly in regions such as the prefrontal cortex, hippocampus, and amygdala. These regions are highly related to cognitive behavior, and therefore their atrophy usually leads to decline in processes such as memory and learning. These cognitive declines can occur in physiological aging and are exacerbated in pathological aging. In this article, we review the cellular processes that underlie the triggers of aging and how they relate to one another, causing the atrophy of nerve tissue that is typical of aging. The main topic of this review to determine the central factor that triggers all the cellular processes that lead to cellular aging and discriminate between normal and pathological aging. Finally, we review how the use of supplements with antioxidant and anti-inflammatory properties reduces the cognitive decline typical of aging, which reinforces the hypothesis of oxidative stress and cellular damage as contributors of physiological atrophy of aging. Moreover, cumulative evidence suggests their possible use as therapies, which improve the aging population's quality of life.

Serological and Molecular Evidence of the Circulation of the Venezuelan Equine Encephalitis Virus Subtype IIIA in Humans, Wild Vertebrates and Mosquitos in the Brazilian Amazon.

Understanding the interaction between viruses and ecosystems in areas with or without anthropic interference can contribute to the organization of public health services, as well as prevention and disease control. An arbovirus survey was conducted at Caxiuanã National Forest, Pará, Brazil, where 632 local residents, 338 vertebrates and 15,774 pools of hematophagous arthropods were investigated. Neutralization antibodies of the Venezuelan Equine Encephalitis virus, subtype IIIA, Mucambo virus (MUCV) were detected in 57.3% and 61.5% of humans and wild vertebrates, respectively; in addition, genomic fragments of MUCV were detected in pool of Uranotaenia (Ura.) geometrica. The obtained data suggest an enzootic circulation of MUCV in the area. Understanding the circulation of endemic and neglected arboviruses, such as MUCV, represents an important health problem for the local residents and for the people living in the nearby urban centers.

A Comparison of Surrogate Behavioral Models for Power Amplifier Linearization under High Sparse Data.

A good approximation to power amplifier (PA) behavioral modeling requires precise baseband models to mitigate nonlinearities. Since digital predistortion (DPD) is used to provide the PA linearization, a framework is necessary to validate the modeling figures of merit support under signal conditioning and transmission restrictions. A field-programmable gate array (FPGA)-based testbed is developed to measure the wide-band PA behavior using a single-carrier 64-quadrature amplitude modulation (QAM) multiplexed by orthogonal frequency-division multiplexing (OFDM) based on long-term evolution (LTE) as a stimulus, with different bandwidths signals. In the search to provide a heuristic target approach modeling, this paper introduces a feature extraction concept to find an appropriate complexity solution considering the high sparse data issue in amplitude to amplitude (AM-AM) and amplitude to phase AM-PM models extraction, whose penalties are associated with overfitting and hardware complexity in resulting functions. Thus, experimental results highlight the model performance for a high sparse data regime and are compared with a regression tree (RT), random forest (RF), and cubic-spline (CS) model accuracy capabilities for the signal conditioning to show a reliable validation, low-complexity, according to the peak-to-average power ratio (PAPR), complementary cumulative distribution function (CCDF), coefficients extraction, normalized mean square error (NMSE), and execution time figures of merit. The presented models provide a comparison with original data that aid to compare the dimension and robustness for each surrogate model where (i) machine learning (ML)-based and (ii) CS interpolate-based where high sparse data are present, NMSE between the CS interpolated based are also compared to demonstrate the efficacy in the prediction methods with lower convergence times and complexities.

First Genomic Evidence of a Henipa-like Virus in Brazil.

The viral genus Henipavirus includes two highly virulent zoonotic viruses of serious public health concern. Hendra henipavirus and Nipah henipavirus outbreaks are restricted to Australia and Southeast Asia, respectively. The Henipavirus genus comprises mostly bat-borne viruses, but exceptions have already been described as novel viruses with rodents and shrews as reservoir animals. In the Americas, scarce evidence supports the circulation of these viruses. In this communication, we report a novel henipa-like virus from opossums (Marmosa demerarae) from a forest fragment area in the Peixe-Boi municipality, Brazil, after which the virus was named the Peixe-Boi virus (PBV). The application of next-generation sequencing and metagenomic approach led us to discover the original evidence of a henipa-like virus genome in Brazil and South America and the original description of a henipa-like virus in marsupial species. These findings emphasize the importance of further studies to characterize PBV and clarify its ecology, impact on public health, and its relationship with didelphid marsupials and henipaviruses.

Curcumin Stimulates the Overexpression of Virulence Factors in Salmonella enterica Serovar Typhimurium: In Vitro and Animal Model Studies.

Salmonella spp. is one of the most common food poisoning pathogens and the main cause of diarrheal diseases in humans in developing countries. The increased Salmonella resistance to antimicrobials has led to the search for new alternatives, including natural compounds such as curcumin, which has already demonstrated a bactericidal effect; however, in Gram-negatives, there is much controversy about this effect, as it is highly variable. In this study, we aimed to verify the antibacterial activity of curcumin against the Salmonella enterica serovar Typhimurium growth rate, virulence, and pathogenicity. The strain was exposed to 110, 220 or 330 µg/mL curcumin, and by complementary methods (spectrophotometric, pour plate and MTT assays), we determined its antibacterial activity. To elucidate whether curcumin regulates the expression of virulence genes, Salmonella invA, fliC and siiE genes were investigated by quantitative real-time reverse transcription (qRT-PCR). Furthermore, to explore the effect of curcumin on the pathogenesis process in vivo, a Caenorhabditis elegans infection model was employed. No antibacterial activity was observed, even at higher concentrations of curcumin. All concentrations of curcumin caused overgrowth (35−69%) and increased the pathogenicity of the bacterial strain through the overexpression of virulence factors. The latter coincided with a significant reduction in both the lifespan and survival time of C. elegans when fed with curcumin-treated bacteria. Our data provide relevant information that may support the selective antibacterial effects of curcumin to reconsider the indiscriminate use of this phytochemical, especially in outbreaks of pathogenic Gram-negative bacteria.

A Crest Factor Reduction Technique for LTE Signals with Target Relaxation in Power Amplifier Linearization.

The signal conditioning treatment to achieve good relation of power with radio-frequency (RF) conversion in conventional transceiver systems require precise baseband models. A developed framework is built to provide a demonstration of the modeling figures of merit with orthogonal frequency division multiplexing (OFDM) support under signal conditioning and transmission restrictions to waveforms with high peak to average power ratio (PAPR) in practical applications. Therefore, peak and average power levels have to be limited to correct high PAPR for a better suited correction power from the amplifier that can lead to compression or clipping in the signal of interest. This work presents an alternative joint crest factor reduction (CFR) algorithm to correct the performance of PAPR. A real-time field-programmable gate array (FPGA) testbed is developed to characterize and measure the behavior of an amplifier using a single-carrier 64-QAM OFDM based on long-term evolution (LTE) downlink at 2.40 GHz as stimulus, across wide modulation bandwidths. The results demonstrate that the CFR accuracy capabilities for the signal conditioning show a reliable clipping reduction to give a smooth version of the clipping signal and provide a factor of correction for the unwanted out-of-band emission validated according to the adjacent channel power ratio (ACPR), PAPR, peak power, complementary cumulative distribution function (CCDF), and error vector magnitude (EVM) figures of merit.

Eventos adversos del nimotuzumab en pacientes con tumor cerebral primario / Adverse events to the nimotuzumab in patients with primary cerebral tumor

Introducción: El nimotuzumab es un anticuerpo monoclonal empleado en el tratamiento de pacientes con tumor cerebral. Dada su novedad se justifica la realización de estudios de farmacovigilancia que avalen su seguridad. Objetivo: Caracterizar los eventos adversos relacionados con este medicamento en la práctica médica habitual. Métodos: Se realizó un estudio descriptivo y transversal de 41 pacientes con tumor cerebral primario tratados con nimotuzumab en el Departamento de Ensayos Clínicos del Hospital Provincial Docente Saturnino Lora Torres de Santiago de Cuba, desde mayo de 2017 hasta abril de 2019. Resultados: En la serie se identificaron 31 eventos adversos, de los cuales 17 eran conocidos y 14 desconocidos. Predominaron la cefalea (80,5 %), la debilidad en miembros inferiores (48,8 %) y la fosfatasa alcalina elevada (41,5 %). Cabe destacar que el total de los efectos no deseados se consideraron ligeros, según su intensidad; reversibles, según sus resultados y sin cambios, según la actitud respecto al medicamento. Conclusiones: Las características de los eventos adversos encontrados se asemejan a las descritas en otros estudios que también avalan la seguridad del fármaco.

Introduction: The nimotuzumab is a monoclonal antibody used in the treatment of patients with cerebral tumor. The realization of pharmaco surveillance studies that guaranteed its security is justified given its new features. Objective: To characterize the adverse events related to this medicine in the habitual medical practice. Methods: A descriptive and cross-sectional study of 41 patients with primary cerebral tumor treated with nimotuzumab in the Clinical Trial Department of Saturnino Lora Torres Teaching Provincial Hospital was carried out in Santiago de Cuba, from May, 2017 to April, 2019. Results: In the series 31 adverse events were identified, of which 17 were known and 14 were unknown. There was a prevalence of the headache (80.5 %), weakness in lower members (48.8 %) and the high alcaline phosphatase (41.5 %). It is necessary to highlight that all the non wanted effects were considered light according to the intensity; reversible, according to the results and without changes, according to the attitude regarding the medicine. Conclusions: The characteristics of the adverse events that were found resemble to those described in other studies that also guarantee the security of the drug.

Accurate Neurosurgery for the Establishment of the Electric Kindling Model of Epilepsy in Mice.

This article describes in detail the essential stereotaxic neurosurgery to develop the electric experimental kindling model in mice. To date, available literature describing the methodology of the kindling model is very poor and usually neglects many relevant details about the neurosurgery, such as the manufacture of the electrodes, accurate stereotaxic coordinates of the amygdala nuclei, and the general surgery procedures (e.g., anesthesia, postsurgical recovery, fit survival of the animal's). The electric kindling model produces a progressive development of generalized tonic-clonic seizures, which can be assessed by electroencephalography and behavioral responses. The seizures displayed are produced by a repeated low-intensity electrical stimulation in specific regions of the brain that is achieved through the previous implantation of electrodes. In this study, the aim was to implant the electrodes in basolateral amygdaloid nucleus (BLA). In order to successfully establish the kindling experimental model, neurosurgery to place the electrodes is an essential step to develop the epileptogenic phenomenon. It crucial that the surgery is carried out with exceptional exactitude, because in that way the experimental model represents an accurate and valid tool to study and understand epilepsy and the results obtained can be used to develop further strategies in epilepsy clinical research.