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BACKGROUND: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero. METHODS: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex. FINDINGS: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings. INTERPRETATION: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted. FUNDING: National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Major dengue epidemics throughout Nicaraguas history have been dominated by 1 of 4 dengue virus serotypes (DENV-1-4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity.

Improving Climate Models and Projections Using Observations Workshop 2023 What: More than 70 experts from research and operational centers came together in a hybrid meeting held at the Massachusetts Institute [...]

Dengue viruses (DENV1-4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.

Abstract Objective To improve hip flexor flexibility, the commonly used hip extension stretch focuses on advancing the pelvis forward in a half-kneeling position, targeting only hip extension. This study aimed to compare the effectiveness of this traditional stretch with a new technique incorporating posterior pelvic tilt. Methods A randomized crossover clinical trial was conducted with in 26 healthy, physically active individuals (52 hips), aged 22.50 ± 4.10 years. Each participant performed both the hip extension stretch and the posterior pelvic tilt stretch (26 hips), with one technique applied to each limb: the posterior pelvic tilt stretch on one limb and the hip extension stretch on the other limb (26 hips). The reactive hip flexor test and active knee extension test were measured pre and post stretching techniques. A repeated measures ANOVA was performed to assess differences between groups. Results There was a significant group-by-time interaction with a medium effect size for the variable related to reactive hip flexor force (F = 4.775, p = 0.034, η2p = 0.087). The posterior pelvic tilt stretch had a statistically significant mean difference of 4.85 N·m (p = 0.003; 95%CI: 1.74; 7.96) compared with the hip extension stretch (mean difference = 0.06 N·m (p = 0.969; 95%CI-3.05; 3.17). No significant differences were found for active knee extension (p > 0.05). Conclusions The results showed that the posterior pelvic tilt stretching technique was effective in reducing the hip reactive flexor force when compared to conventional hip extension stretch.

Major dengue epidemics throughout Nicaragua’s history have been dominated by 1 of 4 dengue virus serotypes (DENV-1–4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity.

Antecedentes: Actualmente, la reproducibilidad y confiabilidad de las clasificaciones radiológicas para fracturas de húmero proximal no han sido demostradas. La clasificación de Neer es la más utilizada, a pesar de mostrar una alta variabilidad interobservador. Objetivo: Evaluar la variabilidad interobservador de tres clasificaciones radiográficas para fracturas de húmero proximal (Neer, Hertel y Mayo-FJD) entre residentes de ortopedia del Centro Médico ABC. Método: Cuatro observadores evaluaron 100 radiografías anteroposteriores de húmero proximal, asignando un grado a la fractura según las clasificaciones Neer, Hertel y Mayo-FJD. La concordancia interobservador se evaluó mediante el coeficiente de correlación kappa. Resultados: Del total de radiografías, el 70% correspondió a pacientes de sexo femenino y el 30% a pacientes de sexo masculino, con una edad promedio de 67 años. La clasificación de Neer mostró la mayor concordancia interobservador (0.350). La clasificación Hertel presentó una concordancia de 0.265, mientras que la clasificación Mayo-FJD mostró una concordancia de 0.345, siendo esta última más consistente entre residentes de mayor jerarquía. Conclusiones: Las clasificaciones evaluadas no proporcionan confiabilidad para describir fracturas de húmero proximal en radiografías anteroposteriores de hombro. Se recomienda analizar la confiabilidad de estas clasificaciones para estudios de tomografía computarizada.

“Synergistic Observing Network for Ocean Prediction (SynObs)” was launched in 2022 as a project of the United Nations Decade of Ocean Science for Sustainable Development to evaluate the importance of ocean observation systems and co-design the future evolution of the ocean observing network. SynObs is currently leading the flagship OSEs/OSSEs, an internationally coordinated activity in which observing system experiments (OSEs) and observing system simulation experiments (OSSEs) are conducted using a variety of ocean and coupled atmosphere–ocean prediction systems to evaluate ocean observation impacts consistent across most prediction systems. The flagship OSEs/OSSEs comprises the ocean prediction (OP) OSEs for high-resolution ocean predictions, the subseasonal-to-seasonal (S2S) OSEs for long-term lead-time coupled ocean–atmosphere predictions, and the OP OSSEs for evaluating new and future observing systems. SynObs plans to use the results of the flagship OSEs to contribute to the reports on the ocean observing network design made by international organizations and projects. Here, we introduce this initiative, and we report on some initial results. Some observation impacts consistent across four ocean prediction systems are found by a preliminary analysis of the analysis runs for the OP OSEs. For example, impacts of the altimetry data on the assimilated sea surface height (SSH) field are generally large in the westerly boundary current regions and around Antarctic Circumpolar Currents where SSH has large variability but are small in the tropical regions, despite the relatively large SSH variability there. The analysis also indicates the possibility that there are some characteristic differences in the observation impacts between low-resolution and eddy-resolving ocean prediction systems. Although OSE outputs of only four ocean prediction systems are available now, we will make further investigation, adding OSE outputs of other prediction systems that will be submitted in the near future.

This study aims to evaluate the impact of the in-situ ocean observations on seasonal forecasts. A series of seasonal reforecasts have been conducted for the period 1993-2015, in which different sets of ocean observations were withdrawn in the production of the ocean initial conditions, while maintaining a strong constrain in sea surface temperature (SST). By comparing the different reforecast sets, it is possible to assess the impact on the forecast of ocean and atmospheric variables. Results show that the in-situ observations have profound and significant impacts on the mean state of forecast ocean and atmospheric variables, which can be classified into different categories: i) impact due to local air-sea interaction, as direct consequence of changes in the mixed layer in the ocean initial conditions, and visible in the early stages of the forecasts; ii) changes due to different ocean dynamical balances, most visible in the Equatorial Pacific in forecasts initialized in May, which amplify and evolve with forecast lead time; iii) changes to the atmospheric circulation resulting from changes in large scale SST gradients; these are non-local, mediated by the atmospheric bridge, and they are obvious from the visible impact of the removing in-situ observations on the Atlantic basin only in the global atmospheric circulation; iv) changes in the atmospheric tropical deep convection associated with the structure of the warm pools. The ocean observations have also a significant impact on the representation of the trends of the ocean initial conditions, which affect the trends in the seasonal forecasts of ocean and atmospheric variables. The impact of the ocean observing system in the Atlantic and extratropics appears dominated by Argo, but this is not the case in the Tropical Pacific, where the other ocean observing systems play a role in constraining the ocean state.

IntroductionInjury prevention and performance enhancement are paramount goals in sports. Myofascial Pain Syndrome, primarily caused by myofascial trigger points, can result in referred pain, stiffness, muscle shortening, and weakness. This study aimed to assess the impact of dry needling (DN) on latent myofascial trigger points on vertical jump performance in female volleyball players.MethodsA single-blind, randomized controlled clinical trial was conducted with twenty-six healthy female volleyball players who had no lower limb injuries in the last six months, exhibited latent trigger points in the triceps surae muscles, and were familiar with the countermovement jump test. Participants were randomly assigned to either a control group or an experimental group (which received a single DN session). Vertical jump performance variables, including jump height as the primary outcome, were assessed using a force platform at five time points: before the intervention, immediately post-treatment, 24 h post-treatment, 72 h post-treatment, and one-week post-intervention.ResultsThe experimental group showed significantly lower values for vertical jump height, flight time, velocity, strength, and power immediately after the needling intervention (p

BackgroundDengue is a mosquito-borne viral disease posing a significant threat to public health. Dengue virus (DENV) evolution is often characterized by lineage turnover, which, along with ecological and immunological factors, has been linked to changes in dengue phenotype affecting epidemic dynamics. Utilizing epidemiologic and virologic data from long-term population-based studies (the Nicaraguan Pediatric Dengue Cohort Study and Nicaraguan Dengue Hospital-based Study), we describe a lineage turnover of DENV serotype 2 (DENV-2) prior to a large dengue epidemic in 2019. Prior to this epidemic, Nicaragua had experienced relatively low levels of DENV transmission from 2014 to 2019, a period dominated by chikungunya in 2014/15 and Zika in 2016.ResultsOur phylogenetic analyses confirmed that all Nicaraguan DENV-2 isolates from 2018 to 2019 formed their own clade within the Nicaraguan lineage of the Asian/American genotype. The emergence of the new DENV-2 lineage reflects a replacement of the formerly dominant clade presiding from 2005 to 2009, a lineage turnover marked by several shared derived amino acid substitutions throughout the genome. To elucidate evolutionary drivers of lineage turnover, we performed selection pressure analysis and reconstructed the demographic history of DENV-2. We found evidence of adaptive evolution by natural selection at the codon level as well as in branch formation.ConclusionsThe timing of its emergence, along with a statistical signal of adaptive evolution and distinctive amino acid substitutions, the latest in the NS5 gene, suggest that this lineage may have increased fitness relative to the prior dominant DENV-2 strains. This may have contributed to the intensity of the 2019 DENV-2 epidemic, in addition to previously identified immunological factors associated with pre-existing Zika virus immunity.

Antecedentes: En los pacientes con lesiones de menisco se presentan de forma concomitante lesiones condrales en el 51% de los casos; la asociación entre la gravedad de la lesión condral y el mayor riesgo de presentar osteoartritis está claramente establecida. Sin embargo, hay escasa información acerca de las características que se asocian a la gravedad de la lesión condral en sujetos con lesiones de menisco mediales y laterales de forma aislada; subgrupo en el que el tratamiento preventivo no está establecido. Objetivo: Identificar las características del paciente con lesión aguda simple de menisco asociadas con la gravedad de la lesión condral. Método: En un estudio transversal se incluyeron sujetos con lesión aguda simple de menisco, se recabó la información de variables clínicas y se evaluó la gravedad de la lesión condral de acuerdo con los criterios de Outerbridge. Resultados: De 70 pacientes, 23 (32.9%) presentaban lesión de tipo I, 34 (48.6%) de tipo II y 13 (18.5%) de tipo III. Los sujetos mayores de 35 años (OR: 3.400; IC95%: 1.198-9.650) y aquellos con etiología degenerativa (OR: 9.333; IC95%: 1.144-76.161) mostraron mayor riesgo de presentar lesiones graves. Conclusiones: La gravedad de la lesión condral en sujetos con lesiones simples de menisco se asocia principalmente a la etiología.

Infectious disease (ID) cohorts are key to advancing public health surveillance, public policies, and pandemic responses. Unfortunately, ID cohorts often lack funding to store and share clinical-epidemiological (CE) data and high-dimensional laboratory (HDL) data long term, which is evident when the link between these data elements is not kept up to date. This becomes particularly apparent when smaller cohorts fail to successfully address the initial scientific objectives due to limited case numbers, which also limits the potential to pool these studies to monitor long-term cross-disease interactions within and across populations. CE data from 9 arbovirus (arthropod-borne viruses) cohorts in Latin America were retrospectively harmonized using the Maelstrom Research methodology and standardized to Clinical Data Interchange Standards Consortium (CDISC). We created a harmonized and standardized meta-cohort that contains CE and HDL data from 9 arbovirus studies from Latin America. To facilitate advancements in cross-population inference and reuse of cohort data, the Reconciliation of Cohort Data for Infectious Diseases (ReCoDID) Consortium harmonized and standardized CE and HDL from 9 arbovirus cohorts into 1 meta-cohort. Interested parties will be able to access data dictionaries that include information on variables across the data sets via Bio Studies. After consultation with each cohort, linked harmonized and curated human cohort data (CE and HDL) will be made accessible through the European Genome-phenome Archive platform to data users after their requests are evaluated by the ReCoDID Data Access Committee. This meta-cohort can facilitate various joint research projects (eg, on immunological interactions between sequential flavivirus infections and for the evaluation of potential biomarkers for severe arboviral disease).

We assess for the first time the impact of in-situ ocean observations on European Centre for Medium-Range Weather Forecasts (ECMWF) sub-seasonal forecasts of both ocean and atmospheric conditions. A series of coupled reforecasts have been conducted for the period 1993-2015, in which different sets of ocean observations were withdrawn in the production of the ocean initial conditions. Removal of all ocean in-situ observations in the initial conditions leads to significant degradation in the forecasts of ocean surface and subsurface mean state at lead times from week 1 to week 4. The negative impact is predominantly caused by the removal of the Argo observing system in recent decades. Changes in the mean state of atmospheric variables are comparatively small but significant in the forecasts of lower and upper atmospheric circulation over large regions. Our results highlight the value of continuous, real-time in-situ observations of the surface and subsurface ocean for coupled forecasts in the sub-seasonal range.

IntroductionThe vaccines developed against COVID-19 have different modes of action, with a primary focus on the spike protein of the virus. Adverse effects following vaccination have been reported, including local and systemic symptoms. Understanding the potential side effects on the urinary tract after vaccination is of importance. Actively investigating and comprehending the potential impact on the urinary tract, we can enhance public health strategies and pave the way for safer and more effective vaccination programs.MethodologyThe study was based on an online survey that included the Spanish Version of the Overactive Bladder Symptom Score (OABSS-S); 2,362 men and women replied to the survey. After the application of the exclusion criteria, 1,563 participants were insured. In the context of COVID-19, individuals were questioned regarding several key factors related to their vaccination status and medical history. These factors included the number of vaccine doses received, the specific type of vaccine administered, whether they had previously contracted COVID-19, and the frequency of prior infections, if applicable.ResultsA total of 1,563 (74.7% women and 27.3% men) subjects between the ages of 18 and 45 completed the survey and were included in the final analyses. The most frequently administered vaccine type was Pfizer-BioNTech (42.2%), and most subjects received three doses. The proportion of females who received the AstraZeneca vaccine and do not require to urinate during the night is significantly higher compared to males (59.1% vs. 33.3%; p

Marine heatwaves (MHWs), defined as prolonged period of extremely warm sea surface temperature (SST), have been receiving a lot of attention in the past decade as their frequency and intensity increase in a warming climate. This paper investigates the extent to which the seasonal occurrence and duration of MHWs can be predicted with the European Centre for Medium-Range Weather Forecast (ECMWF) operational seasonal forecast system. The prediction of the occurrence of MHW events, the number of MHW days per season, and their intensity and spatial extent are derived from seasonal SST forecasts and evaluated against an observation-based SST analysis using both deterministic and probabilistic metrics over the 1982–2021 period. Forecast scores show useful skill in predicting the occurrence of MHWs globally for the two seasons following the starting date. The skill is the highest in the El Niño region, the Caribbean, the wider tropics, the north-eastern extra-tropical Pacific, and southwest of the extra-tropical basins. The skill is not as good for other midlatitude eastern basins nor for the Mediterranean, with the forecast system being able to represent the low-frequency modulation of MHWs but showing poor skill in predicting the interannual variability of the MHW characteristics. Linear trend analysis shows an increase in MHW occurrence at a global scale, which the forecasts capture well.

The presented study introduces a semi-analytical circuit model (CM) to fully characterize a dielectric unit cell structure made by blocks instead of applying the effective medium theory. A fitting strategy is used to a obtain a better understanding of the properties of the unit cell. Then, the approach is used to develop a semi-analytical model, showing a good agreement with the scattering parameters extracted from a full-wave simulator. By tuning the dielectric material, our model can describe the behaviour of unit cells with different permittivities and electrical sizes. Finally, as an application for the analyzed dielectric unit cells, transmitarrays to generate orbital angular momentum (OAM) waves are designed and 3D-printed. The measured results show good performance for different OAM modes at 31 GHz.

Abstract Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.

Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort in Nicaragua. Children protected from symptomatic infections had more anti-envelope (E) and anti-nonstructural protein 1 (NS1) total immunoglobulin G (IgG), IgG4, and greater Fc effector functions than those with symptoms. Fc effector functions were also associated with protection from hemorrhagic manifestations in the pre-symptomatic group. Furthermore, in vitro virological assays using these plasma samples revealed that protection mediated by antibody-dependent complement deposition was associated with both lysis of virions and DENV-infected cells. These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines.

In the context of ecological transition, the use of wine by-products for industrial applications is a major challenge. Wine lees, the second wine by-product in terms of quantity, are a source of nutrients that can be used for stimulating the growth of microorganisms. Here, white wine lees were used as a stimulating agent for the growth of wine lactic acid bacteria (LAB) and to promote wine malolactic fermentation (MLF) in red wine.

There is growing demand for seasonal forecast products for marine applications. The availability of consistent and sufficiently long observational records of ocean variables permits the assessment of the spatial distribution of the skill of ocean variables from seasonal forecasts. Here we use state-of-the-art temporal records of sea surface temperature (SST), sea surface height (SSH) and upper 300m ocean heat content (OHC) to quantify the distribution of skill, up to 2 seasons ahead, of two operational seasonal forecasting systems contributing to the seasonal multi-model of the Copernicus Climate Change Services (C3S). This study presents the spatial distribution of the skill of the seasonal forecast ensemble mean in terms of anomaly correlation and root mean square error and compares it to the persistence and climatological benchmarks. The comparative assessment of the skill among variables sheds light on sources/limits of predictability at seasonal time scales, as well as the nature of model errors. Beyond these standard verification metrics, we also evaluate the ability of the models to represent the observed long-term trends. Results show that long-term trends contribute to the skill of seasonal forecasts. Although the forecasts capture the long-term trends in general, some regional aspects remain challenging. Part of these errors can be attributed to specific aspects of the ocean initialization, but others, such as the overestimation of the warming in the Eastern Pacific are also influenced by model error. Skill gains can be obtained by improving the trend representation in future forecasting systems. In the meantime, a forecast calibration procedure that corrects the linear trends can produce substantial skill gains. The results show that calibrated seasonal forecasts beat both the climatological and persistence benchmark almost at every location for all initial dates and lead times. Results demonstrate the value of the seasonal forecasts for marine applications and highlight the importance of representing the decadal variability and trends in ocean heat content and sea level.

Introduction: The methods used in the diagnosis of pregnancy in rats mostly have disadvantages, such as: the need for a high degree of professional expertise, material costs, the need for anesthesia and the impossibility of diagnosing on the first days. However, the determination of body weight is easily obtained data, supported by a simple and non-invasive technique, which represents an advantage over other methods. Objective: To determine on which day of gestation the increase in body weight reaches sufficient significance to establish the diagnosis of pregnancy in Wistar rats. Material and Methods: It is an observational, prospective, longitudinal study. A total of 37 females were selected and divided into two groups: 24 pregnant rats (RG) and 13 non-pregnant rats (RNG). Both groups were weighed on gestation days 0, 2, 6, 9, 13 and 16. The variation in body weight was analyzed through the days. Results: Despite the body differences between groups on days 2 and 6, the results were inconclusive for this stage. The GR reached a minimum average increase of 27.5 g towards day 9, for this same day the average increase in the GR and RNG was 36.1 g and 9.17 g, respectively. Conclusions: Body weight from day 9 of gestation reaches sufficient relevance for the diagnosis of pregnancy in heterozygous Wistar rats, but not before day 6.

Abstract Background Dengue is a mosquito-borne viral disease posing a significant threat to public health. Dengue virus (DENV) evolution is often characterized by lineage turnover, which, along with ecological and immunological factors, has been linked to changes in dengue phenotype affecting epidemic dynamics. Utilizing epidemiologic and virologic data from long-term population-based studies (the Nicaraguan Pediatric Dengue Cohort Study and Nicaraguan Dengue Hospital-based Study), we describe a lineage turnover of DENV serotype 2 (DENV-2) prior to a large dengue epidemic in 2019. Prior to this epidemic, Nicaragua had experienced relatively low levels of DENV transmission from 2014 to 2019, a period dominated by chikungunya in 2014/15 and Zika in 2016. Results Our phylogenetic analyses confirmed that all Nicaraguan DENV-2 isolates from 2018 to 2019 formed their own clade within the Nicaraguan lineage of the Asian/American genotype. The emergence of the new DENV-2 lineage reflects a replacement of the formerly dominant clade presiding from 2005 to 2009, a lineage turnover marked by several shared derived amino acid substitutions throughout the genome. To elucidate evolutionary drivers of lineage turnover, we performed selection pressure analysis and reconstructed the demographic history of DENV-2. We found evidence of adaptive evolution by natural selection at the codon level as well as in branch formation. Conclusions The timing of its emergence, along with a statistical signal of adaptive evolution and distinctive amino acid substitutions, the latest in the NS5 gene, suggest that this lineage may have increased fitness relative to the prior dominant DENV-2 strains. This may have contributed to the intensity of the 2019 DENV-2 epidemic, in addition to previously identified immunological factors associated with pre-existing Zika virus immunity.

Dengue virus serotypes 1 to 4 (DENV1–4) and Zika virus (ZIKV) are mosquito-borne flaviviruses that induce both virus-specific and broadly reactive antibodies. A first DENV infection is thought to induce antibodies that wane over 2 years to titers that can subsequently enhance severe dengue disease. Secondary DENV infection with a different serotype is thought to induce stable, cross-serotype protective antibodies. Low dengue disease incidence after the recent Zika pandemic led to the hypothesis that ZIKV infection is also transiently cross protective. We investigated antibody kinetics in 4189 children up to 11 years after one and multiple DENV and ZIKV infections in longitudinal cohorts in Nicaragua. We used a DENV inhibition enzyme-linked immunosorbent assay (iELISA), which measures antibodies associated with protection against dengue and Zika disease and with enhancement of dengue disease severity. Unexpectedly, we found that overall DENV iELISA titers stabilized by 8 months after primary DENV infection to a half-life longer than a human life and waned, although gradually, after secondary DENV infection. Similarly, DENV iELISA titers were stable or rose after primary ZIKV infection but declined in individuals with histories of DENV and ZIKV infection. In contrast, kinetics of anti-ZIKV antibodies after ZIKV infection were similar regardless of prior DENV immunity. We observed heterogeneity in DENV iELISA titer, suggesting that individual antibody titer set point, rather than waning, is important for future dengue disease risk. Together, these findings change our understanding of anti-flavivirus antibody kinetics and have implications for measuring vaccine efficacy and for predicting future dengue and Zika outbreaks.

The focus of many Ph.D. programs in research-intense universities across disciplines is to prepare its graduate students to enter the professoriate with the skills needed to be successful in meeting institutional research expectations. Although most tenure-track positions include teaching responsibilities, few programs prepare faculty for teaching at the post-secondary level. As faculty at a research-intensive university, we developed a pilot course focused on preparing future faculty to develop the knowledge, confidence, and understanding of usefulness of constructs related to teaching in university classrooms. Overall, all ten participants found the course useful and provided feedback that will inform future iterations of the course. Misalignment of course expectations are discussed as are constructs perceived as most helpful to their future teaching.