Exploring the Genomic Dynamics of the Monkeypox Epidemic in Paraguay.

In recent months, Paraguay has been grappled with a notable monkeypox outbreak, straining its healthcare infrastructure. The sudden spike in cases underlines the imperative need for a comprehensive understanding of the virus's dynamics, enabling the formulation of robust containment measures. To address this challenge, our team joined forces with the Central Public Health Laboratory of Asunción and the Pan-American Health Organization. Through this collaboration, we employed portable whole-genome sequencing combined with phylodynamic analysis to examine the MPXV strains circulating in Paraguay. Our genomic monitoring approach has produced the first 30 whole-genome sequences from Paraguay, all of which were identified under lineage IIb. Interestingly, our data suggest that the origin of the monkeypox virus in Paraguay at the beginning of 2022 can be traced back to Brazil. This introduction subsequently catalyzed further community spread that was further exacerbated by several independent introduction events as time progressed. These findings not only shed light on the transmission patterns of the virus but also highlight the pivotal role such insights play in sculpting effective response strategies and driving impactful public health measures. Furthermore, our findings strongly advocate intensified surveillance at international borders, ensuring swift detection and proactive countermeasures against potential outbreaks in the future.

Rapid Epidemic Expansion of Chikungunya Virus East/Central/South African Lineage, Paraguay.

The spread of Chikungunya virus is a major public health concern in the Americas. There were >120,000 cases and 51 deaths in 2023, of which 46 occurred in Paraguay. Using a suite of genomic, phylodynamic, and epidemiologic techniques, we characterized the ongoing large chikungunya epidemic in Paraguay.

Retrospective Spatio-Temporal Dynamics of Dengue Virus 1, 2 and 4 in Paraguay.

Dengue virus (DENV) has been a major public health concern in Paraguay, with frequent outbreaks occurring since early 1988. Although control measures have been implemented, dengue remains a significant health threat in the country, and continued efforts are required for prevention and control. In response to that, in collaboration with the Central Public Health Laboratory in Asunción, we conducted a portable whole-genome sequencing and phylodynamic analysis to investigate DENV viral strains circulating in Paraguay over the past epidemics. Our genomic surveillance activities revealed the co-circulation of multiple DENV serotypes: DENV-1 genotype V, the emerging DENV-2 genotype III, BR4-L2 clade, and DENV-4 genotype II. Results additionally highlight the possible role of Brazil as a source for the international dispersion of different viral strains to other countries in the Americas emphasizing the need for increased surveillance across the borders, for the early detection and response to outbreaks. This, in turn, emphasizes the critical role of genomic surveillance in monitoring and understanding arbovirus transmission and persistence locally and over long distances.

Rapid epidemic expansion of chikungunya virus-ECSA lineage in Paraguay.

The spread of vector-borne viruses, such as CHIKV, is a significant public health concern in the Americas, with over 120,000 cases and 51 deaths in 2023, of which 46 occurred in Paraguay. Using a suite of genomic, phylodynamic, and epidemiological techniques, we characterized the ongoing large CHIKV epidemic in Paraguay. Article Summary Line: Genomic and epidemiological characterization of the ongoing Chikungunya virus epidemic in Paraguay.

Self-Medication Practices, Use of Brand-Name, and Over-the-Counter Medicines by Peruvian Older Adults.

Background: Older adults are a particularly vulnerable group to drug use and self-medication. The aim of the study was to evaluate self-medication as a factor associated with the purchase of brand-name and over-the-counter (OTC) drugs in older adults in Peru. Methods: A secondary analysis was performed using an analytical cross-sectional design of data from a nationally representative survey from 2014 to 2016. The exposure variable was self-medication, defined as the purchase of medicines without a prescription. The dependent variables were purchases of brand-name and OTC drugs, both as a dichotomous response (yes/no). Information of sociodemographic variables, health insurance, and the types of drugs purchased by the participants was collected. Crude prevalence ratios (PR) were calculated and adjusted using generalized linear models of the Poisson family, considering the complex sample of the survey. Results: In this study, 1,115 respondents were evaluated, with a mean age of 63.8 years and a male proportion of 48.2%. The prevalence of self-medication was 66.6%, while the proportions of purchases of brand-name and OTC drugs were 62.4% and 23.6%, respectively. The adjusted Poisson regression analysis revealed an association between self-medication and the purchase of brand-name drugs (adjusted PR [aPR]=1.09; 95% confidence interval [CI]: 1.01-1.19). Likewise, self-medication was associated with the purchase of OTC medications (aPR=1.97; 95%CI: 1.55-2.51). Conclusions: This study evidenced a high prevalence of self-medication in Peruvian older adults. Two-thirds of the surveyed people bought brand-name drugs, whereas one-quarter bought OTC drugs. Self-medication was associated with a greater likelihood of buying brand-name and OTC drugs.

Un nuevo desafío para los médicos del Paraguay: la nefritis intersticial crónica de comunidades agrícolas (CINAC)

RESUMEN Se presenta revisión narrativa sobre nefritis intersticial crónica de comunidades agrícolas (CINAC, siglas del inglés Chronic Interstitial Nephritis in Agricultural Communities). Se discute la etiología, manifestaciones clínicas, manejo diagnóstico y terapéutico de esta afección.

ABSTRACT A narrative review on Chronic Interstitial Nephritis in Agricultural Communities (CINAC) is presented. The etiology, clinical manifestations, diagnostic and therapeutic management of this condition are discussed.

Genomic epidemiology of the SARS-CoV-2 epidemic in Brazil

The high numbers of COVID-19 cases and deaths in Brazil have made Latin America an epicentre of the pandemic. SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, but important gaps remain in our understanding of virus transmission dynamics at a national scale. We use 17,135 near-complete genomes sampled from 27 Brazilian states and bordering country Paraguay. From March to November 2020, we detected co-circulation of multiple viral lineages that were linked to multiple importations (predominantly from Europe). After November 2020, we detected large, local transmission clusters within the country. In the absence of effective restriction measures, the epidemic progressed, and in January 2021 there was emergence and onward spread, both within and abroad, of variants of concern and variants under monitoring, including Gamma (P.1) and Zeta (P.2). We also characterized a genomic overview of the epidemic in Paraguay and detected evidence of importation of SARS-CoV-2 ancestor lineages and variants of concern from Brazil. Our findings show that genomic surveillance in Brazil enabled assessment of the real-time spread of emerging SARS-CoV-2 variants.

Corrigendum: Object-Based Analyses in FIJI/ImageJ to Measure Local RNA Translation Sites in Neurites in Response to Aß1-42 Oligomers.

[This corrects the article DOI: 10.3389/fnins.2020.00547.].

Relación entre el consumo materno de carne vacuna durante el embarazo y los niveles de ferritina en el cordón umbilical / Relationship between maternal beef consumption during pregnancy and umbilical cord ferritin concentration / Relação entre o consumo materno de carne bovina durante a gravidez e os níveis de ferritina no cordão umbilical

Antecedentes: la nutrición durante el embarazo impacta en la salud del recién nacido, con efectos a nivel epigenético determinando consecuencias neurológicas a largo plazo. Las necesidades de hierro durante el embarazo se estiman en 27 mg/día. El hierro hemo que se absorbe mejor se encuentra en la carne. La determinación de ferritina en sangre de cordón umbilical permite evaluar los depósitos de hierro alcanzados durante la etapa fetal. Sus niveles se asociaron con efectos a largo plazo sobre el desarrollo infantil. Objetivos: el objetivo de este estudio de carácter exploratorio es determinar la relación entre el consumo de carnes rojas durante el tercer trimestre de gestación y el nivel de ferritina en el cordón umbilical. Métodos: se realizó un estudio observacional descriptivo con datos recolectados prospectivamente durante un año en el Departamento de Neonatología del Centro Hospitalario Pereira Rossell (CHPR) en Montevideo, Uruguay. Un total de 188 pacientes cumplieron los criterios de inclusión. Se extrajo sangre del cordón umbilical después de un pinzamiento estricto del cordón pasado un minuto de vida. La ferritina se midió utilizando el método de quimioinmunofluorescencia. Se aplicó una encuesta nutricional materna (cualitativo-cuantitativa) que midió la frecuencia de consumo de alimentos con fuente de hierro y las cantidades aproximadas consumidas durante el último trimestre del embarazo. Esta encuesta se centró en el consumo materno de carne vacuna como principal fuente de hierro hemínico en Uruguay. Se analizó la relación entre estas variables. Resultados: el déficit latente de hierro (ferritina en el cordón umbilical <100 ng/ml) se asoció con un menor consumo de carne vacuna durante el embarazo. Valor p de Fisher: 0,0133, OR: 3,71, IC del 95% (1,25-11,05). Conclusiones: este estudio considera adecuada la evidencia que relaciona que los niveles bajos de consumo total de hierro y de carne vacuna durante el tercer trimestre de gestación determinarán un mayor riesgo de déficit latente de hierro y de ferritina medido en el cordón umbilical. Los niveles descendidos de ferritina en cordón umbilical se asocian con un mayor riesgo de efectos adversos a largo plazo sobre la mielinización y el desarrollo neurocognitivo.

Background: nutrition during pregnancy impacts the foetus and the newborn health, it has consequences at the epigenetic level and determines long-term neurological consequences. Iron requirements during pregnancy are estimated at 27 mg/day. Iron is blood absorption from is most efficient from beef. Umbilical cord blood ferritin levels can be used to assess iron deposits reached during the foetal stage. Ferritin levels are linked to the child's long-term development. Objective: this exploratory study's objective is to determine the relationship between beef consumption during the first quarter of pregnancy and ferritin levels in the umbilical cord. Methods: we carried out a descriptive, observational study with prospectively collected data for one-year at the Neonatology Department of the Pereira Rossell Hospital Center (CHPR) in Montevideo, Uruguay. A total of 188 patients met the inclusion criteria. We extracted umbilical cord blood after a strict cord clamping after one minute of life. Ferritin was measured using the chemoimmunofluorescence method. We carried out a maternal nutritional survey using a qualitative-quantitative method and measured the frequency and approximate quantity of iron source food consumption during the last quarter of pregnancy. This survey was focused on maternal beef consumption as the major heme iron source in Uruguay. We analyzed the relationship between these variables. Results: latent iron deficiency (ferritin in the umbilical cord <100 ng / ml) was associated with lower beef consumption during pregnancy. Fisher p-value: 0.0133, OR: 3.71, 95% CI (1.25 - 11.05). Conclusions: this study agrees with the evidence that shows that low levels of total iron and beef consumption during pregnancy determine an increased risk of latent iron deficiency and lower levels of ferritin in newborns, and therefore, greater risk of long-term adverse effects on myelination and neurocognitive development.

Contexto: a nutrição durante a gravidez tem impacto sobre a saúde do recém-nascido, com efeitos no nível epigenético, determinando consequências neurológicas a longo prazo. As necessidades de ferro durante a gravidez são estimadas em 27 mg / dia. O ferro heme de melhor absorção e aquele encontrado na carne vacuna. A determinação da ferritina no sangue do cordão umbilical permite avaliar os depósitos de ferro atingidos na fase fetal. Seus níveis foram associados a efeitos de longo prazo no desenvolvimento das crianças. Objetivos: o objetivo deste estudo exploratório é determinar a relação entre o consumo de carne vermelha durante o terceiro trimestre de gestação e o nível de ferritina no cordão umbilical. Métodos: foi realizado um estudo observacional descritivo com dados coletados prospectivamente durante um ano no Departamento de Neonatologia do Centro Hospitalar Pereira Rossell (CHPR) em Montevidéu, Uruguai. Um total de 188 pacientes cumpriram os critérios de inclusão. O sangue do cordão umbilical foi coletado após clampeamento estrito do cordão após um minuto de vida da criança. A ferritina foi medida pelo método de quimioimunofluorescência. Aplicamos um inquérito nutricional materno (qualitativo-quantitativo) que mediu a frequência de consumo de alimentos com fonte de ferro e as quantidades aproximadas consumidas durante o último trimestre da gravidez. Esta pesquisa enfocou o consumo materno de carne bovina como principal fonte de ferro heme no Uruguai. A relação entre essas variáveis foi analisada. Resultados: a deficiência latente de ferro (ferritina no cordão umbilical <100 mg / ml) foi associada ao menor consumo de carne bovina durante a gestação. Valor de p de Fisher: 0,0133, OR: 3,71, IC 95% (1,25-11,05). Conclusões: este estudo concorda com as evidências que relacionam que os baixos níveis de ferro total e consumo de carne bovina durante o terceiro trimestre de gestação determinam um maior risco de déficit de ferro latente e ferritina mensurado no cordão umbilical. A redução dos níveis de ferritina no cordão umbilical está associada a um risco aumentado de efeitos adversos de longo prazo na mielinização e no desenvolvimento neurocognitivo.

Local Translation in Nervous System Pathologies.

Dendrites and axons can extend dozens to hundreds of centimeters away from the cell body so that a single neuron can sense and respond to thousands of stimuli. Thus, for an accurate function of dendrites and axons the neuronal proteome needs to be asymmetrically distributed within neurons. Protein asymmetry can be achieved by the transport of the protein itself or the transport of the mRNA that is then translated at target sites in neuronal processes. The latter transport mechanism implies local translation of localized mRNAs. The role of local translation in nervous system (NS) development and maintenance is well established, but recently there is growing evidence that this mechanism and its deregulation are also relevant in NS pathologies, including neurodegenerative diseases. For instance, upon pathological signals disease-related proteins can be locally synthesized in dendrites and axons. Locally synthesized proteins can exert their effects at or close to the site of translation, or they can be delivered to distal compartments like the nucleus and induce transcriptional responses that lead to neurodegeneration, nerve regeneration and other cell-wide responses. Relevant key players in the process of local protein synthesis are RNA binding proteins (RBPs), responsible for mRNA transport to neurites. Several neurological and neurodegenerative disorders, including amyotrophic lateral sclerosis or spinal motor atrophy, are characterized by mutations in genes encoding for RBPs and consequently mRNA localization and local translation are impaired. In other diseases changes in the local mRNA repertoire and altered local protein synthesis have been reported. In this review, we will discuss how deregulation of localized translation at different levels can contribute to the development and progression of nervous system pathologies.

RNA Localization and Local Translation in Glia in Neurological and Neurodegenerative Diseases: Lessons from Neurons.

Cell polarity is crucial for almost every cell in our body to establish distinct structural and functional domains. Polarized cells have an asymmetrical morphology and therefore their proteins need to be asymmetrically distributed to support their function. Subcellular protein distribution is typically achieved by localization peptides within the protein sequence. However, protein delivery to distinct cellular compartments can rely, not only on the transport of the protein itself but also on the transport of the mRNA that is then translated at target sites. This phenomenon is known as local protein synthesis. Local protein synthesis relies on the transport of mRNAs to subcellular domains and their translation to proteins at target sites by the also localized translation machinery. Neurons and glia specially depend upon the accurate subcellular distribution of their proteome to fulfil their polarized functions. In this sense, local protein synthesis has revealed itself as a crucial mechanism that regulates proper protein homeostasis in subcellular compartments. Thus, deregulation of mRNA transport and/or of localized translation can lead to neurological and neurodegenerative diseases. Local translation has been more extensively studied in neurons than in glia. In this review article, we will summarize the state-of-the art research on local protein synthesis in neuronal function and dysfunction, and we will discuss the possibility that local translation in glia and deregulation thereof contributes to neurological and neurodegenerative diseases.

Epidemiologic History and Genetic Diversity Origins of Chikungunya and Dengue Viruses, Paraguay.

Paraguay has been severely affected by emergent Zika and chikungunya viruses, and dengue virus is endemic. To learn more about the origins of genetic diversity and epidemiologic history of these viruses in Paraguay, we deployed portable sequencing technologies to strengthen genomic surveillance and determine the evolutionary and epidemic history of arthropod-borne viruses (arboviruses). Samples stored at the Paraguay National Central Laboratory were sequenced and subjected to phylogenetic analysis. Among 33 virus genomes generated, we identified 2 genotypes of chikungunya and 2 serotypes of dengue virus that circulated in Paraguay during 2014-2018; the main source of these virus lineages was estimated to be Brazil. The evolutionary history inferred by our analyses precisely matched the available travel history of the patients. The genomic surveillance approach used was valuable for describing the epidemiologic history of arboviruses and can be used to determine the origins and evolution of future arbovirus outbreaks.

Object-Based Analyses in FIJI/ImageJ to Measure Local RNA Translation Sites in Neurites in Response to Aß1-42 Oligomers.

Subcellular protein delivery is especially important in signal transduction and cell behavior, and is typically achieved by localization signals within the protein. However, protein delivery can also rely on localization of mRNAs that are translated at target sites. Although once considered heretical, RNA localization has proven to be highly conserved in eukaryotes. RNA localization and localized translation are especially relevant in polarized cells like neurons where neurites extend dozens to hundreds of centimeters away from the soma. Local translation confers dendrites and axons the capacity to respond to their environment in an acute manner without fully relying on somatic signals. The relevance of local protein synthesis in neuron development, maintenance and disease has not been fully acknowledged until recent years, partly due to the limited amount of locally produced proteins. For instance, in hippocampal neurons levels of newly synthesized somatic proteins can be more than 20-30 times greater than translation levels of neuritic proteins. Thus local translation events can be easily overlooked under the microscope. Here we describe an object-based analysis used to visualize and quantify local RNA translation sites in neurites. Newly synthesized proteins are tagged with puromycin and endogenous RNAs labeled with SYTO. After imaging, signals corresponding to neuritic RNAs and proteins are filtered with a Laplacian operator to enhance the edges. Resulting pixels are converted into objects and selected by automatic masking followed by signal smoothing. Objects corresponding to RNA or protein and colocalized objects (RNA and protein) are quantified along individual neurites. Colocalization between RNA and protein in neurites correspond to newly synthesized proteins arising from localized RNAs and represent localized translation sites. To test the validity of our analyses we have compared control neurons to Aß1 - 42-treated neurons. Aß is involved in the pathology of Alzheimer's disease and was previously reported to induce local translation in axons and dendrites which in turn contributes to the disease. We have observed that Aß increases the synthesis of neuritic proteins as well as the fraction of translating RNAs in distal sites of the neurite, suggesting an induction of local protein synthesis. Our results thus confirm previous reports and validate our quantification method.

Carcinoma mucoepidermoide de bajo grado de glándula salival menor de lengua en un paciente pediátrico / Low grade mucoepidermoid carcinoma of a minor salivary gland of the tongue in a paediatric patient

No disponible

Doble conducto auditivo interno / Internal auditory canal duplicity

No disponible

Parameters of skull vibration-induced nystagmus in normal subjects.

HYPOTHESIS: The knowledge of vibration-induced nystagmus test (SVINT) values in the normal population is highly relevant to provide a rapid orientation on the diagnosis attitude in a patient with vertigo. BACKGROUND: Although mastoid bone vibration should only induce nystagmus in the presence of vestibular asymmetry, it has also been reported in normal individuals raising doubts as to how to interpret the SVINT. To date, no population studies involving the use of the SVINT and that establish normative values have been published. METHODS: This study was carried out at two tertiary healthcare centres on a total of 122 subjects. We stimulated at three frequencies (30, 60 and 100 Hz), in increasing order, first stimulating the right mastoid and then the left mastoid, and waiting for 30 s between each stimulus. The response was recorded with a videonystagmography system. The following variables were evaluated in each subject: the mean and maximum speed of the slow phase of nystagmus, the frequency of the nystagmatic response (NR) and the component and direction of the rapid phase of nystagmus. RESULTS: Only 26 subjects (20.5%) of the subjects studied here (122 subjects) developed any kind of nystagmatic response and 96 subjects (79.5%) did not display any response. Stimulation at 100 Hz provoked the largest number of responses (p = 0.04), while there was no difference in the number of responses induced by 30 and 60 Hz stimulations (p = 0.85). The frequency of nystagmus was ≤ 0.7 n/s in 80.8% of the positive responses. The mean velocity of the horizontal component of the NR was 2.2°/s (SD 1.6) and that of the vertical component was 1.3°/s (SD 1.2). CONCLUSIONS: Healthy subjects do not generally develop to NR upon vibratory stimulation and only 20% of the subjects studied here developed any kind of NR, this being a slow and inconsistent response of low frequency. The establishment of normal values contributes to improve the orientation in clinical practice in the pathological population and this opens possibilities for tackling more reliable studies in this population.

Accounting for no net loss: A critical assessment of biodiversity offsetting metrics and methods.

Biodiversity offset strategies are based on the explicit calculation of both losses and gains necessary to establish ecological equivalence between impact and offset areas. Given the importance of quantifying biodiversity values, various accounting methods and metrics are continuously being developed and tested for this purpose. Considering the wide array of alternatives, selecting an appropriate one for a specific project can be not only challenging, but also crucial; accounting methods can strongly influence the biodiversity outcomes of an offsetting strategy, and if not well-suited to the context and values being offset, a no net loss outcome might not be delivered. To date there has been no systematic review or comparative classification of the available biodiversity accounting alternatives that aim at facilitating metric selection, and no tools that guide decision-makers throughout such a complex process. We fill this gap by developing a set of analyses to support (i) identifying the spectrum of available alternatives, (ii) understanding the characteristics of each and, ultimately (iii) making the most sensible and sound decision about which one to implement. The metric menu, scoring matrix, and decision tree developed can be used by biodiversity offsetting practitioners to help select an existing metric, and thus achieve successful outcomes that advance the goal of no net loss of biodiversity.

Evolución Genética del Virus Influenza A(H1N1) pdm09 en Paraguay 2009-2016

RESUMEN Una cepa triple reasortante del virus Influenza A emergió en al año 2009 dando origen a una pandemia que alcanzó a Paraguay en junio del mismo año. Con el fin de investigar la evolución genética del virus influenza A (H1N1) pdm09 en Paraguay fueron analizadas las secuencias nucleotídicas del Gen de la Hemaglutinina de 20 cepas de Influenza A(H1N1)pdm09, aisladas en el Centro Nacional de Influenza de Paraguay entre los años 2009 y 2016, y secuenciadas en el Centro Colaborador de OPS/OMS en Atlanta USA. El análisis filogenético muestra la circulación de al menos 5 grupos genéticos bien diferenciados de Influenza A(H1N1)pdm09 en Paraguay desde el 2009. Solamente los virus aislados en el 2016 pertenecen al sub Grupo genético 6B.1 en el cual se encuentra la actual cepa vacunal A/Michigan/45/2015 recomendada para el hemisferio Sur desde el año 2017. Los virus circulantes en años anteriores pertenecen a grupos antigénicamente indistinguibles de la cepa vacunal previa A/California/7/2009. No se encontraron diferencias resaltantes en las secuencias de los virus, relacionadas a severidad clínica ni a distribución geográfica. Los resultados de este estudio reafirman la necesidad de una vigilancia virológica sistemática para orientar el establecimiento de estrategias adecuadas de prevención y control de la influenza.

ABSTRACT A triple reassortant strain of Influenza A virus emerged in 2009, leading to a pandemic that reached Paraguay by June the same year. In order to investigate the genetic evolution of influenza A (H1N1)pdm09 virus in Paraguay, we analized the nucleotide sequences of the Hemagglutinin gene of 20 Influenza A (H1N1)pdm09 strains, isolated at the Paraguayan National Influenza Centre between 2009 and 2016, and sequenced at the PAHO/WHO Collaborating Center in Atlanta, USA. Phylogenetic analysis shows the circulation of at least 5 well-differentiated genetic groups of Influenza A (H1N1) pdm09 in Paraguay since 2009. Only the viruses isolated in 2016 belong to genetic subgroup 6B.1, the same as the current vaccine strain A/Michigan/45/2015, recommended for the Southern hemisphere since 2017. The viruses circulated previous years belong to groups antigenically indistinguishable from the previous vaccine strain A/California/7/2009. No significant differences were found in sequences of the viruses, related to clinical severity or geographic distribution. The results of this study reaffirm the need for systematic virological surveillance to guide the establishment of adequate strategies for the prevention and control of influenza.