Microclimate factors related to dengue virus burden clusters in two endemic towns of Mexico.

In dengue-endemic areas, transmission control is limited by the difficulty of achieving sufficient coverage and sustainability of interventions. To maximize the effectiveness of interventions, areas with higher transmission could be identified and prioritized. The aim was to identify burden clusters of Dengue virus (DENV) infection and evaluate their association with microclimatic factors in two endemic towns from southern Mexico. Information from a prospective population cohort study (2·5 years of follow-up) was used, microclimatic variables were calculated from satellite information, and a cross-sectional design was conducted to evaluate the relationship between the outcome and microclimatic variables in the five surveys. Spatial clustering was observed in specific geographic areas at different periods. Both, land surface temperature (aPR 0·945; IC95% 0·895-0·996) and soil humidity (aPR 3·018; IC95% 1·013-8·994), were independently associated with DENV burden clusters. These findings can help health authorities design focused dengue surveillance and control activities in dengue endemic areas.

A practical guide to time-resolved fluorescence microscopy and spectroscopy.

Time-correlated single photon counting (TCSPC) coupled with confocal microscopy is a versatile biophysical tool that enables real-time monitoring of biomolecular dynamics across many timescales. With TCSPC, Fluorescence correlation spectroscopy (FCS) and pulsed interleaved excitation-Förster resonance energy transfer (PIE-FRET) are collected simultaneously on diffusing molecules to extract diffusion characteristics and proximity information. This article is a guide to calibrating FCS and PIE-FRET measurements with several biological samples including liposomes, streptavidin-coated quantum dots, proteins, and nucleic acids for reliable determination of diffusion coefficients and FRET efficiency. The FRET efficiency results are also compared to surface-attached single molecules using fluorescence lifetime imaging microscopy (FLIM-FRET). Combining the methods is a powerful approach to revealing mechanistic details of biological processes and pathways.

Public Acceptance of Measures to Control Infectious Diseases Under Different Scenarios of Severity and Transmissibility.

OBJECTIVES: Public health measures to control future epidemic threats of contagious disease, such as new variants of COVID-19, may be usefully informed by evidence about how acceptable they are likely to be, and the circumstances that condition this acceptance. This study considers how the acceptability of nonpharmaceutical interventions (NPIs) might depend on scenarios about the severity and transmissibility of the disease. METHODS: A telephone survey was conducted among a representative cross-sectional sample of the Spanish adult population. Each respondent was randomly assigned to 1 of 4 possible hypothetical scenarios about the severity and transmissibility of the disease. Participants' responses about the acceptability of 11 NPI under this scenario were analyzed using multivariate regression and latent class cluster analysis. RESULTS: A high risk of severe disease increases the acceptability of mask wearing, social distancing outdoors, lockdown, and isolation of infected cases, close contacts, and the vulnerable. A scenario in which the disease is highly transmissible would increase the acceptability of NPI that restrict movement and isolation. Most respondents would broadly accept most NPI in situations when either the severity or transmissibility was high. CONCLUSIONS: This study showed that people are more willing to accept NPIs such as mask wearing, social distancing outdoors, lockdown, and isolation in severe disease scenarios. A highly transmissible disease scenario increases the acceptability of NPIs that isolate. A majority would broadly accept NPIs to counter public health emergencies, whereas 3% to 9% of the population would always be strongly against.

Effects of the sunscreen ultraviolet filter oxybenzone (benzophenone-3) on the seagrass Posidonia oceanica (L.) Delile and its associated N2 fixers.

Oxybenzone/benzophenone-3 (BP-3) is one of the most detrimental organic ultraviolet filters for marine biota, leading to legislative measures banning its presence in commercial sunscreen formulations of several countries. It remains poorly explored how this contaminant is currently threatening the persistence of critical ecosystems for conservation in the Mediterranean, such as Posidonia oceanica meadows, but it is essential for promoting sustainable coastal tourism. Our investigation aimed to determine the effects of BP-3 on P. oceanica under a short-term laboratory setup, recreating summer conditions while testing three environmentally relevant concentrations for Mallorca, Spain (minimum: 53.6 ng L-1, maximum: 557.5 ng L-1 and increased: 1115 ng L-1) and a control (0 ng L-1). Primary productivity was unaffected by the treatments, however, a reduction in leaf chlorophyll content and nitrogen fixation activity associated with rhizomes was evidenced under BP-3 addition. This may be related with oxidative damage, as reactive oxygen species production and catalase activity in P. oceanica leaves were the highest even at minimum BP-3 concentrations. Alkaline phosphatase rates showed inverted trends between old leaves and rhizomes, being enhanced in the former under BP-3 addition and reduced in the latter. These results are of great relevance for the future management of P. oceanica meadows, elucidating that even minimum concentrations of BP-3 reported in coastal waters of Mallorca can induce elevated levels of oxidative stress in the seagrass, that lead to impairments in its photosynthetic pigments production and supply of essential nutrients through belowground tissues.

Considerations in Forehead Reduction for Men.

Although frontal prominence is an infrequent benign defect that causes no sequelae, it gives the patient distress due to its unaesthetic visual aspect. Proper surgical recontouring of the forehead can radically change one's appearance. In consequence, different techniques have been proposed for its management and correction. The aim of this study is to describe a surgical algorithm to treat male patients with forehead reduction to soften the "forceful" look. An observational cross-sectional study was conducted at the head and neck surgery ward of a general hospital between 2019 and 2022. We performed 35 forehead reduction operations on male patients. The median age was 29 years (range, 26-32 years). The forehead reduction procedures performed was categorized as follows: 27 anterior table osteotomy and 8 anterior table osteotomy contouring. Median forehead reduction was 2.7 mm (range, 2-3.2 mm). The average medical follow-up for patients was 6 months, with an interval ranging from 4 to 8 months. Surgery of the forehead in properly selected male patients is sufficiently safe that it can be done for entirely aesthetic reasons. The choice of surgical technique depends on the presence or absence of the pneumatized frontal sinus. If the frontal sinus is not pneumatized, an anterior table contouring is performed and if the frontal sinus is pneumatized, an anterior table osteotomy is preferred.

House Condition Scoring Scale as a Risk Indicator of Infestation by Aedes in Two Mexican Localities.

Mexico has shown an increase in dengue incidence rates. There are factors related to the location that determine housing infestation by Aedes. This study aimed to determine factors associated with housing infestation by immature forms of Aedes spp. in the dengue endemic localities of Axochiapan and Tepalcingo, Mexico, from 2014 to 2016. A cohort study was carried out. Surveys and inspections of front- and backyards were conducted every 6 months, looking for immature forms of Aedes spp. A house condition scoring scale was developed using three variables (house maintenance, tidiness of the front- and backyards, and shading of the front- and backyards). Multiple and multilevel regression logistic analysis were conducted considering the housing infestation as the outcome and the household characteristics observed 6 months before the outcome as factors; this was adjusted by time (seasonal and cyclical variations of the vector). The infestation oscillated between 5.8% of the houses in the second semester of 2015 and 29.3% in the second semester of 2016. The factors directly associated with housing infestation by Aedes were the house condition score (adjusted odds ratio [aOR]: 1.64; 95% CI: 1.40-1.91) and the previous record of housing infestation (aOR: 2.99; 95% CI: 2.00-4.48). Moreover, the breeding-site elimination done by house residents reduced the housing infestation odds by 81% (95% CI: 25-95%). These factors were independent of the seasonal and cyclical variations of the vector. In conclusion, our findings could help to focalize antivectorial interventions in dengue-endemic regions with similar demographic and socioeconomic characteristics.

The Insulin Receptor Substrate 2 Mediates the Action of Insulin on HeLa Cell Migration via the PI3K/Akt Signaling Pathway.

Insulin signaling plays an important role in the development and progression of cancer since it is involved in proliferation and migration processes. It has been shown that the A isoform of the insulin receptor (IR-A) is often overexpressed, and its stimulation induces changes in the expression of the insulin receptor substrates (IRS-1 and IRS-2), which are expressed differently in the different types of cancer. We study the participation of the insulin substrates IRS-1 and IRS-2 in the insulin signaling pathway in response to insulin and their involvement in the proliferation and migration of the cervical cancer cell line. Our results showed that under basal conditions, the IR-A isoform was predominantly expressed. Stimulation of HeLa cells with 50 nM insulin led to the phosphorylation of IR-A, showing a statistically significant increase at 30 min (p ≤ 0.05). Stimulation of HeLa cells with insulin induces PI3K and AKT phosphorylation through the activation of IRS2, but not IRS1. While PI3K reached the highest level at 30 min after treatment (p ≤ 0.05), AKT had the highest levels from 15 min (p ≤ 0.05) and remained constant for 6 h. ERK1 and ERK2 expression was also observed, but only ERK2 was phosphorylated in a time-dependent manner, reaching a maximum peak 5 min after insulin stimulation. Although no effect on cell proliferation was observed, insulin stimulation of HeLa cells markedly promoted cell migration.

Sunscreen exposure interferes with physiological processes while inducing oxidative stress in seagrass Posidonia oceanica (L.) Delile.

The effects of a commercial sunscreen mixture on the Mediterranean seagrass Posidonia oceanica were investigated, evaluating its response in physiological processes and biochemical indicators of oxidative stress. Short-term laboratory experiments were conducted recreating summer conditions, and two sunscreen concentrations were tested in whole P. oceanica plants placed inside aquaria. Although primary productivity of leaf segments seemed to benefit from sunscreen addition, probably due to inorganic nutrients released, the rest of the biological parameters reflected possible impairments in the overall functioning of P. oceanica as a result of oxidative damages. Chlorophyll production and nitrogen fixation associated with old leaves were inhibited under high sunscreen concentrations, which concurred with elevated reactive oxygen species production, catalase activity and polyphenols content in the seagrass leaves. These results emphasize the importance of directing future investigations on determining which specific components of sunscreen products are likely threatening the wellbeing of critical species, such as P. oceanica.

Surgical Treatment and Reconstruction of Nasal Defects According to the Aesthetic Subunits Principles.

The aim of this study was to determine the prevalence of nasal skin cancer, its location by facial aesthetic subunits and the type of reconstructive procedures performed for each nasal subunit after excision for nasal skin tumors. Observational cross-sectional study of all consecutive patients with the diagnosis of skin tumor located in the nasal unit, treated from 2018 to 2019 by the department of head and neck surgery of a general hospital. 60 patients were treated with nasal skin tumors excisions. A total of 52 patients (86,6%) had basal cell skin cancer, 7 (11,6%) had squamous cell skin cancer and 1 (1,6%) had melanoma. Fifty-nine patients (98.33%) presented a primary tumor and just 1 case (1,66%) recived a previous surgical treatment. Regardless of the type of tumor, the tip subunit was the most often involved with 29 (48,33%) cases in total. Despite of the nasal aesthetic subunit affected, the most frequent type of procedure used for reconstruction was the rotation or advancement flap, based on aesthetic nasal subunits, which was performed in 39 cases (65%). Nasal reconstruction after skin cancer can be very complex, especially since all patients have high expectations about the results. In order to achieve good results, there is a necessity for careful analysis of the defect, correct planning and excellent technical execution of the procedures Frequently, staged procedures will be needed to achieve an optimal result.

Sodium Caseinate in Combination With Daunorubicin or Cytarabine Improves Survival of Mice With Long-established Leukemia.

BACKGROUND/AIM: Although acute myeloid leukemia (AML) has traditionally been considered an oncological emergency and initiation of therapy is believed to be crucial to minimizing disease-related morbidity and mortality, it has also been suggested that a certain delay in treatment has no negative consequences in terms of response, early mortality, or survival. We aimed to determine the effect of administration of sodium caseinate (SC), a salt of casein, the main milk protein, with cytarabine or with daunorubicin on survival in mice with well-established leukemia. MATERIALS AND METHODS: To assay the time of establishment of leukemia in the bone marrow, Balb/c mice were inoculated with 2.5×10 5 WEHI-3 cells/mouse and after 3, 6 and 9 days were euthanized. Bone marrow mononuclear cells (BM-MNCs) of the femur were obtained and cultured for 120 h with or without rmIL-3 and cell proliferation was evaluated by the crystal violet technique. Then, the effect of administrating SC-cytarabine or SC-daunorubicin on survival rates of mice with well-established leukemia was assayed. Another group of Balb/c mice was inoculated with WEHI-3 cell and after 10 days mice were treated with SC-cytarabine or SC-daunorubicin for 40 days. Survival rates were recorded daily and in surviving mice, the prevalence of bone marrow proliferation after treatment was assayed by the crystal violet technique. RESULTS: The assay on the time of establishment of leukemia shows that in 9 days leukemia cells accumulate in the bone marrow in sufficient quantities to sustain an in vitro culture in the absence of growth factors, and we, thus, used this as a criterion of well-established leukemia. When mice with a burden of leukemic cells of more than 9 days were treated with SC-cytarabine or SC-daunorubicin, this resulted in 55% survival for both treatments, and the proliferation assays showed that the bone marrow retained its normal proliferation capacity. CONCLUSION: SC-cytarabine or SC-daunorubicin treatment prolonged the survival rate of Balb/c mice with a burden of well-established leukemia, and there was no negative impact on bone marrow functionality; however, SC-cytarabine or SC-daunorubicin combination options need to be sought to increase survival beyond 40 days.

An all optical approach for comprehensive in-operando analysis of radiative and nonradiative recombination processes in GaAs double heterostructures.

We demonstrate an all optical approach that can surprisingly offer the possibility of yielding much more information than one would expect, pertinent to the carrier recombination dynamics via both radiative and nonradiative processes when only one dominant deep defect level is present in a semiconductor material. By applying a band-defect state coupling model that explicitly treats the inter-band radiative recombination and Shockley-Read-Hall (SRH) recombination via the deep defect states on an equal footing for any defect center occupation fraction, and analyzing photoluminescence (PL) as a function of excitation density over a wide range of the excitation density (e.g., 5-6 orders in magnitude), in conjunction with Raman measurements of the LO-phonon plasmon (LOPP) coupled mode, nearly all of the key parameters relevant to the recombination processes can be obtained. They include internal quantum efficiency (IQE), minority and majority carrier density, inter-band radiative recombination rate (Wr), minority carrier nonradiative recombination rate (Wnr), defect center occupation fraction (f), defect center density (Nt), and minority and majority carrier capture cross-sections (σt and σtM). While some of this information is thought to be obtainable optically, such as IQE and the Wr/Wnr ratio, most of the other parameters are generally considered to be attainable only through electrical techniques, such as current-voltage (I-V) characteristics and deep level transient spectroscopy (DLTS). Following a procedure developed herein, this approach has been successfully applied to three GaAs double-heterostructures that exhibit two distinctly different nonradiative recombination characteristics. The method greatly enhances the usefulness of the simple PL technique to an unprecedented level, facilitating comprehensive material and device characterization without the need for any device processing.

First Evidence of Horizontal Transmission by Fecal Shedding of Dengue Virus 4 Among Aedes aegypti Larvae (Diptera: Culicidae) Under Laboratory Conditions.

The transmission pathways of dengue virus (DENV) among mosquitoes are a topic that has gained relevance in recent years because they could explain the maintenance of the virus in the wild independently of the human-mosquito horizontal transmission cycle. In this regard, Aedes aegypti larvae exposed to supernatants of C6/36 cells infected with DENV-4 were evaluated for virus excretion in feces and viability of infection in immature stages (larvae). The results demonstrate that larvae excrete DENV-4 in their feces with the potential to at least infect immature individuals of the same species. A horizontal transmission pathway of larvae-larvae DENV-4 under laboratory conditions is suggested.

Factors associated with endoparasites and ectoparasites in domiciled dogs in the metropolitan area of Toluca, México / Factores asociados con la presencia de endoparásitos y ectoparásitos en perros domiciliados de la zona metropolitana de Toluca, México.

Introduction: Endoparasites and ectoparasites in dogs are of global distribution. The close relationship between dogs and man implies a risk for the transmission of zoonotic parasites. Therefore, it is necessary to determine the parasites hosted by dogs in specific areas and the factors associated with their presence. Objectives: To identify and to estimate the prevalence of endoparasites and ectoparasites in domiciled dogs in the Metropolitan area of Toluca, México, and the prevalence of D. caninum in fleas of the genus Ctenocephalides spp. Materials and methods: We collected samples from 402 domiciled dogs in four reference hospitals in the area in Toluca. We diagnosed endoparasites using direct smear, flotation, and sedimentation techniques and we performed the taxonomic identification of ectoparasites. Finally, the molecular diagnosis of D. caninum in fleas was made using the polymerase chain reaction technique (PCR). Results: A total of 37.2% of dogs were positive for endoparasites; the genera or species identified were Toxocara spp., Giardia spp., Ancylostoma spp., Cystoisospora spp., D. caninum, Taenia spp., and Trichuris vulpis; the prevalence of ectoparasites was 13.13%. We identified fleas of the species Ctenocephalides felis, Ctenocephalides canis; only one animal was parasitized with Rhipicephalus sanguineus and another one with Trichodectes canis; the prevalence of D. caninum in fleas was 9.5%. Conclusion: The prevalence of endoparasites was 37.2% while that of ectoparasites was 13.1%; this is the first analysis of endoparasites and ectoparasites conducted in the same population of dogs in México together with the molecular diagnosis of D. caninum in fleas.

Introducción. Los endoparásitos y ectoparásitos en perros son de distribución mundial. La estrecha relación entre los perros y el hombre implica un riesgo de transmisión de parasitosis zoonóticas, por lo cual es necesario conocer las especies que parasitan a los perros de esta zona y determinar los factores asociados. Objetivos. Estimar la prevalencia de endoparásitos y ectoparásitos, identificarlos en perros domiciliados de la zona metropolitana de Toluca, México, y determinar la prevalencia de Dipyilidium caninum en pulgas del género Ctenocephalides spp. Materiales y métodos. Se recolectaron muestras de 402 perros que fueron llevados a consulta en cuatro hospitales de referencia de Toluca. En el diagnóstico de endoparásitos, se utilizaron las técnicas coproparasitoscópicas de frotis directo, flotación y sedimentación; además, se recolectaron ectoparásitos para su identificación taxonómica. Por último, la detección de D. caninum en pulgas se hizo mediante la reacción en cadena de la polimerasa (PCR). Resultados. El 37,2 % de los perros resultó positivo para endoparásitos. Los géneros o especies identificados fueron Toxocara spp., Giardia spp., Ancylostoma spp., Cystoisospora spp., D. caninum, Taenia spp. y Trichuris vulpis. Se determinó una prevalencia de ectoparásitos de 13,13 %. Se identificaron pulgas de las especies Ctenocephalides felis y C. canis, en tanto que solo un animal presentó parasitosis por Rhipicephalus sanguineus y otro por Trichodectes canis. La prevalencia de D. caninum en pulgas fue del 9,5 %. Conclusión. La prevalencia de endoparásitos fue de 37,2 % y, la de ectoparásitos, de 13,1 %. Por primera vez en México se hizo un análisis de endoparásitos y ectoparásitos en una misma población de perros, así como el diagnóstico molecular de D. caninum.

Factores asociados con la presencia de endoparásitos y ectoparásitos en perros domiciliados de la zona metropolitana de Toluca, México / Factors associated with endoparasites and ectoparasites in domiciled dogs in the metropolitan area of Toluca, México

Resumen | Introducción. Los endoparásitos y ectoparásitos en perros son de distribución mundial. La estrecha relación entre los perros y el hombre implica un riesgo de transmisión de parasitosis zoonóticas, por lo cual es necesario conocer las especies que parasitan a los perros de esta zona y determinar los factores asociados. Objetivos. Estimar la prevalencia de endoparásitos y ectoparásitos, identificarlos en perros domiciliados de la zona metropolitana de Toluca, México, y determinar la prevalencia de Dipyilidium caninum en pulgas del género Ctenocephalides spp. Materiales y métodos. Se recolectaron muestras de 402 perros que fueron llevados a consulta en cuatro hospitales de referencia de Toluca. En el diagnóstico de endoparásitos, se utilizaron las técnicas coproparasitoscópicas de frotis directo, flotación y sedimentación; además, se recolectaron ectoparásitos para su identificación taxonómica. Por último, la detección de D. caninum en pulgas se hizo mediante la reacción en cadena de la polimerasa (PCR). Resultados. El 37,2 % de los perros resultó positivo para endoparásitos. Los géneros o especies identificados fueron Toxocara spp., Giardia spp., Ancylostoma spp., Cystoisospora spp., D. caninum, Taenia spp. y Trichuris vulpis. Se determinó una prevalencia de ectoparásitos de 13,13 %. Se identificaron pulgas de las especies Ctenocephalides felis y C. canis, en tanto que solo un animal presentó parasitosis por Rhipicephalus sanguineus y otro por Trichodectes canis. La prevalencia de D. caninum en pulgas fue del 9,5 %. Conclusión. La prevalencia de endoparásitos fue de 37,2 % y, la de ectoparásitos, de 13,1 %. Por primera vez en México se hizo un análisis de endoparásitos y ectoparásitos en una misma población de perros, así como el diagnóstico molecular de D. caninum.

Abstract | Introduction: Endoparasites and ectoparasites in dogs are of global distribution. The close relationship between dogs and man implies a risk for the transmission of zoonotic parasites. Therefore, it is necessary to determine the parasites hosted by dogs in specific areas and the factors associated with their presence. Objectives: To identify and to estimate the prevalence of endoparasites and ectoparasites in domiciled dogs in the Metropolitan area of Toluca, México, and the prevalence of D. caninum in fleas of the genus Ctenocephalides spp. Materials and methods: We collected samples from 402 domiciled dogs in four reference hospitals in the area in Toluca. We diagnosed endoparasites using direct smear, flotation, and sedimentation techniques and we performed the taxonomic identification of ectoparasites. Finally, the molecular diagnosis of D. caninum in fleas was made using the polymerase chain reaction technique (PCR). Results: A total of 37.2% of dogs were positive for endoparasites; the genera or species identified were Toxocara spp., Giardia spp., Ancylostoma spp., Cystoisospora spp., D. caninum, Taenia spp., and Trichuris vulpis; the prevalence of ectoparasites was 13.13%. We identified fleas of the species Ctenocephalides felis, Ctenocephalides canis; only one animal was parasitized with Rhipicephalus sanguineus and another one with Trichodectes canis; the prevalence of D. caninum in fleas was 9.5%. Conclusion: The prevalence of endoparasites was 37.2% while that of ectoparasites was 13.1%; this is the first analysis of endoparasites and ectoparasites conducted in the same population of dogs in México together with the molecular diagnosis of D. caninum in fleas.

Risk Prediction of Death in Inpatient Adults With COVID-19 from Mexico.

Background: There is substantial variation in COVID-19 lethality across countries. In addition, in countries with populations with extreme economic inequalities, such as Mexico, there are regional and local differences in risk factors for COVID-19 death. The goal of this study was to test the hypothesis that the risk of death in Mexican COVID-19 patients was associated with the time between symptom onset and hospitalization and/or with the healthcare site. Also, death prognostic models were developed. Methods: The study included two COVID-19 inpatient cohorts, one prospective and one retrospective from Chiapas, Mexico. Demographic, clinical and laboratory variables were collected, and the diagnosis of SARS-CoV-2 infection was performed using RT-qPCR in samples collected seven days since symptom onset. The 30-day mortality, since symptom onset, was the outcome, and clinical variables at the first 48 hours of hospitalization were independent factors. Multivariate logistic regression analyses were conducted. Results: Of the 392 patients included, 233 died (59.4%). The time between symptom onset and hospitalization, the healthcare site and sex were not related to the 30-day mortality. Three death prognostic models were developed (AUC between 0.726 and 0.807). Age, LDH, AST, and lymphocyte count were included in all models, OSI-WHO Classification (Non-invasive ventilation or high-flow oxygen, and mechanical ventilation with or without organ support/ECMO) and leukocyte count in two models, and diabetes and diarrhea in one model. Conclusion: The population evaluated had underlying deteriorated health before COVID-19 compared with regional and country population. The factors that determine the COVID-19 mortality risk in a relatively healthy population are sex, age and comorbidities. However, as this study shows, when populations have underlying poor health, some of these factors lose their associations with mortality risk, and others become more important.

Use of the Purse-String Suture to Conservatively Manage a Cornual Ectopic Pregnancy.

We report the successful management of a 31-year-old female, treated by cornual wedge resection. The patient suffered from vaginal spotting and lower abdominal pain. Transvaginal ultrasonography revealed a 4-5 cm right cornual pregnancy and beta-human chorionic gonadotropin was measured to be 614.7 IU/L. This ectopic pregnancy was removed via a laparotomy with cornual wedge resection and right salpingectomy.

Comparison of the Impact of Zika and Dengue Virus Infection, and Other Acute Illnesses of Unidentified Origin on Cognitive Functions in a Prospective Cohort in Chiapas Mexico.

Zika has been associated with a variety of severe neurologic manifestations including meningitis and encephalitis. We hypothesized that it may also cause mild to subclinical neurocognitive alterations during acute infection or over the long term. In this observational cohort study, we explored whether Zika cause subclinical or mild neurocognitive alterations, estimate its frequency and duration, and compare it to other acute illnesses in a cohort of people with suspected Zika infection, in the region of Tapachula in Chiapas, Mexico during 2016-2018. We enrolled patients who were at least 12 years old with suspected Zika virus infection and followed them up for 6 months. During each visit participants underwent a complete clinical exam, including a screening test for neurocognitive dysfunction (Montreal Cognitive Assessment score). We enrolled 406 patients [37 with Zika, 73 with dengue and 296 with other acute illnesses of unidentified origin (AIUO)]. We observed a mild and transient impact over cognitive functions in patients with Zika, dengue and with other AIUO. The probability of having an abnormal MoCA score (<26 points) was significantly higher in patients with Zika and AIUO than in those with dengue. Patients with Zika and AIUO had lower memory scores than patients with dengue (Zika vs. Dengue: -0.378, 95% CI-0.678 to -0.078; p = 0.014: Zika vs. AIUO 0.264, 95% CI 0.059, 0.469; p = 0.012). The low memory performance in patients with Zika and AIUO accounts for most of the differences in the overall MoCA score when compared with patients with dengue. Our results show a decrease in cognitive function during acute illness and provides no evidence to support the hypothesis that Zika might cause neurocognitive alterations longer than the period of acute infection or different to other infectious diseases. While effects on memory or perhaps other cognitive functions over the long term are possible, larger studies using more refined tools for neurocognitive functioning assessment are needed to identify these. Trial Registration: NCT02831699.

Oleoylethanolamide Delays the Dysfunction and Death of Purkinje Cells and Ameliorates Behavioral Defects in a Mouse Model of Cerebellar Neurodegeneration.

Oleoylethanolamide (OEA) is an endocannabinoid that has been proposed to prevent neuronal damage and neuroinflammation. In this study, we evaluated the effects of OEA on the disruption of both cerebellar structure and physiology and on the behavior of Purkinje cell degeneration (PCD) mutant mice. These mice exhibit cerebellar degeneration, displaying microtubule alterations that trigger the selective loss of Purkinje cells and consequent behavioral impairments. The effects of different doses (1, 5, and 10 mg/kg, i.p.) and administration schedules (chronic and acute) of OEA were assessed at the behavioral, histological, cellular, and molecular levels to determine the most effective OEA treatment regimen. Our in vivo results demonstrated that OEA treatment prior to the onset of the preneurodegenerative phase prevented morphological alterations in Purkinje neurons (the somata and dendritic arbors) and decreased Purkinje cell death. This effect followed an inverted U-shaped time-response curve, with acute administration on postnatal day 12 (10 mg/kg, i.p.) being the most effective treatment regimen tested. Indeed, PCD mice that received this specific OEA treatment regimen showed improvements in motor, cognitive and social functions, which were impaired in these mice. Moreover, these in vivo neuroprotective effects of OEA were mediated by the PPARα receptor, as pretreatment with the PPARα antagonist GW6471 (2.5 mg/kg, i.p.) abolished them. Finally, our in vitro results suggested that the molecular effect of OEA was related to microtubule stability and structure since OEA administration normalized some alterations in microtubule features in PCD-like cells. These findings provide strong evidence supporting the use of OEA as a pharmacological agent to limit severe cerebellar neurodegenerative processes.

Improved Survival of Leukemic Mice Treated with Sodium Caseinate in Combination with Daunorubicin without Toxicity.

In recent years, low doses of chemotherapy have been resumed and explored for the treatment of acute myeloid leukemia. Thus, CPX-351, a dual-drug liposomal encapsulation of cytarabine and daunorubicin, was approved by the US Food and Drug Administration, to deliver a synergistic 5 : 1 molar drug ratio into leukemia cells to a greater extent than normal bone marrow cells and significantly enhance survival compared with conventional treatment in older and newly diagnosed AML patients, but overall survival rate remains low; therefore, the need for new therapeutic options continues. Sodium caseinate (SC), a salt of casein, the main milk protein, has cytotoxic effect in leukemia cell lines, but promotes proliferation of hematopoietic normal cells, while its administration in leukemic mice promotes survival for more than 40 days, but bone marrow surviving mice still harbour leukemic cells, but it is not known whether the combination with cytarabine or daunorubicin can improve survival without damaging normal hematopoietic cells. Here, it is shown that, in vitro, the combination of the IC25 of SC-cytarabine or SC-daunorubicin synergizes in the elimination of leukemic cells, with evident induction of apoptosis, while the proliferation of mononuclear cells of bone marrow is not affected. In leukemic mice, the combined administration of SC-daunorubicin or SC-cytarabine promotes the highest survival rate at 40 days; in addition, no autoproliferating cells were detected in the bone marrow of survivors of more than 60 days, evidence of eradication of leukemic cells, but only the bone marrow of mice treated with the SC-daunorubicin combination proliferated in the presence of interleukin-3, which shows that this combination is not toxic to normal bone marrow cells, thus emerging as a possible antileukemic agent.

Universal influenza vaccination: a Mexican Expert Position Paper.

OBJECTIVE: Influenza is a costly disease for the population. It is a cause of seasonal morbidity and mortality, epidemics and pandemics or syndemics. Given the variability of the virus, surveillance systems are implemented in order to update the strains and include them in the annual influenza vaccine. This vaccine is currently recommended in some high-risk groups. However, universal vaccination remains controversial. To evaluate the evidence and describe the position of a panel of experts on the relevance of universal vaccination against influenza virus. MATERIAL AND METHODS: Five clinical questions were asked, whereby a systematic search of the literature in electronic sources and a Delphi panel were carried out. The evidence was analyzed, and recommendations were issued by the experts. RESULTS: The group of experts recommends vaccinating the population starting at six months of age and include people who live with egg protein allergy, with comorbidities (diabetes, obesity, cancer), health workers and pregnant women. CONCLUSIONS: Vaccination, starting with vulnerable groups, is a necessary, ethical and cost-effective strategy. However, expanding the coverage to achieve universal vaccination could reduce the transmission of the disease and its consequences in the population.

OBJETIVO: La influenza es una enfermedad costosa para la población. Es causa de morbimortalidad estacional, epidemias y pandemias o sindemias. Debido a la variabilidad del virus, se implementan sistemas de vigilancia para actualizar las cepas e incluirlas en la vacuna antiinfluenza anual. Actualmente se recomienda esta vacuna en algunos grupos de alto riesgo. Sin embargo, la vacunación universal es aún controvertida. Evaluar la evidencia y describir la posición de un panel de expertos sobre la pertinencia de la vacunación universal contra el virus de influenza. MATERIAL Y MÉTODOS: Se realizaron cinco preguntas clínicas, con las que se realizó una búsqueda sistemática de la literatura en fuentes electrónicas y un panel Delphi. Se analizó la evidencia y se emitieron recomendaciones por los expertos. RESULTADOS: El grupo de expertos recomienda vacunar a la población desde los seis meses de edad e incluir a personas que viven con alergia a la proteína del huevo, con comorbilidades (diabetes, obesidad, cáncer), trabajadores de la salud y embarazadas. CONCLUSIONES: La vacunación, iniciando con los grupos vulnerables, es una estrategia necesaria, ética y costo-efectiva. Sin embargo, extender la cobertura para lograr la vacunación universal podría disminuir la transmisión de la enfermedad y sus consecuencias en la población.