Structure and function of an effector domain in antiviral factors and tumor suppressors SAMD9 and SAMD9L.

SAMD9 and SAMD9L (SAMD9/9L) are antiviral factors and tumor suppressors, playing a critical role in innate immune defense against poxviruses and the development of myeloid tumors. SAMD9/9L mutations with a gain-of-function (GoF) in inhibiting cell growth cause multisystem developmental disorders including many pediatric myelodysplastic syndromes. Predicted to be multidomain proteins with an architecture like that of the NOD-like receptors, SAMD9/9L molecular functions and domain structures are largely unknown. Here, we identified a SAMD9/9L effector domain that functions by binding to double-stranded nucleic acids (dsNA) and determined the crystal structure of the domain in complex with DNA. Aided with precise mutations that differentially perturb dsNA binding, we demonstrated that the antiviral and antiproliferative functions of the wild-type and GoF SAMD9/9L variants rely on dsNA binding by the effector domain. Furthermore, we showed that GoF variants inhibit global protein synthesis, reduce translation elongation, and induce proteotoxic stress response, which all require dsNA binding by the effector domain. The identification of the structure and function of a SAMD9/9L effector domain provides a therapeutic target for SAMD9/9L-associated human diseases.

Monodelphis domestica as a Fetal Intra-Cerebral Inoculation Model for Zika Virus Pathogenesis.

Monodelphis domestica (the laboratory opossum) is a marsupial native to South America. At birth, these animals are developmentally equivalent to human embryos at approximately 5 weeks of gestation, which, when coupled with other characteristics including the size of the animals, the development of a robust immune system during juvenile development, and the relative ease of experimental manipulation, have made M. domestica a valuable model in many areas of biomedical research. However, their suitability as models for infectious diseases, especially neurotropic viruses such as Zika virus (ZIKV), is currently unknown. Here, we describe the replicative effects of ZIKV using a fetal intra-cerebral model of inoculation. Using immunohistology and in situ hybridization, we found that opossum embryos and fetuses are susceptible to infection by ZIKV administered intra-cerebrally, that the infection persists, and that viral replication results in neural pathology and may occasionally result in global growth restriction. These results demonstrate the utility of M. domestica as a new animal model for investigating ZIKV infection in vivo and facilitate further inquiry into viral pathogenesis, particularly for those viruses that are neurotropic, that require a host with the ability to sustain sustained viremia, and/or that may require intra-cerebral inoculations of large numbers of embryos or fetuses.

Human SAMD9 is a poxvirus-activatable anticodon nuclease inhibiting codon-specific protein synthesis.

As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase that specifically cleaves phenylalanine tRNA (tRNAPhe), resulting in codon-specific ribosomal pausing and stress signaling. While SAMD9 ACNase activity is normally latent in cells, it can be activated by poxvirus infection or rendered constitutively active by SAMD9 mutations associated with various human disorders, revealing tRNAPhe depletion as an antiviral mechanism and a pathogenic condition in SAMD9 disorders. We identified the N-terminal effector domain of SAMD9 as the ACNase, with substrate specificity primarily determined by a eukaryotic tRNAPhe-specific 2'-O-methylation at the wobble position, making virtually all eukaryotic tRNAPhe susceptible to SAMD9 cleavage. Notably, the structure and substrate specificity of SAMD9 ACNase differ from known microbial ACNases, suggesting convergent evolution of a common immune defense strategy targeting tRNAs.

Mean platelet volume, platelet count, and neutrophil/lymphocyte ratio in drug-naïve patients with schizophrenia: a cross-sectional study.

Introduction: Mean platelet volume (MPV), platelet count, and neutrophil/lymphocyte ratio (NLR) have been proposed to be biomarkers of the chronic inflammatory process in schizophrenia and indicative of increased cardiovascular risk. Objective: To describe MPV, total platelet count (PLT), and NLR between healthy controls and patients with schizophrenia to determine the correlation between these parameters and the duration of untreated psychosis (DUP). Methods: In a retrospective cross-sectional study, we included 175 patients with schizophrenia who had never received psychiatric treatment, and who had undergone blood biometry and blood chemistry within 24 h of admission. Laboratory studies were determined by the impedance method on Coulter ac-T 5 diff hematological equipment. Results: Mean platelet volume levels in patients with schizophrenia were higher than in healthy controls but not statistically significant. The receiver operating characteristic curve for this parameter shows that the optimal cutoff point of agreement was 8.95 fL, with sensitivity and specificity for schizophrenia of 52% and 67%, respectively, and the area under the curve (AUC) was 0.580 (p = 0.079). DUP had no significant correlation with the blood parameters analyzed. Conclusion: The results partially support the hypothesis that MPV, platelet count, and NLR is related to schizophrenia, and further research is needed to establish whether there is an underlying chronic inflammatory process.

Local Percutaneous Radiofrequency for Chronic Plantar Fasciitis.

Plantar fasciitis is the most common cause of heel pain. It accounts for 80% of the cases and has an estimated prevalence rate of up to 7% in the general population, with bilateral involvement in 20% to 30% of those patients. This condition affects people of working age, thereby limiting and diminishing their quality of life. There are a wide range of treatment options for the management of plantar fasciitis that include both conservative and surgical treatments. Although surgical treatment based on partial or total plantar fascia release has success rates of some 70% to 90%, it is not free of complications. These complications, soft-tissue healing problems, superficial infection, or longitudinal arch collapse in cases of a greater than 40% release of the fascia. Bipolar radiofrequency appears to be a safe procedure for refractory plantar fasciitis that can provide outcomes equivalent to open plantar fascia release with less morbidity. The purpose of this article is to describe the local percutaneous radiofrequency technique for patients with chronic, recalcitrant plantar fasciitis.

Infected Mosquitoes Have Altered Behavior to Repellents: A Systematic Review and Meta-analysis.

Here we conducted a systematic review and meta-analysis to reach a consensus on whether infected and uninfected mosquitoes respond differently to repellents. After screening 2,316 published studies, theses, and conference abstracts, we identified 18 studies that tested whether infection status modulated the effectiveness of repellents. Thirteen of these studies had outcomes available for meta-analysis, and overall, seven repellents were tested (typically DEET with 62% of outcomes), six mosquito species had repellence behaviors measured (typically Aedes aegypti (L.) (Diptera: Culicidae) mosquitoes with 71% of outcomes), and a broad diversity of infections were tested including Sindbis virus (Togaviridae: Alphavirus) (33% of outcomes), Dengue (Flaviviridae: Flavivirus) (31%), malaria (Plasmodium berghei Vincke & Lips (Haemospororida: Plasmodiidae) or P. falciparum Welch (Haemospororida: Plasmodiidae); 25%), Zika (Flaviviridae: Flavivirus) (7%), and microsporidia (4%). Pooling all outcomes with meta-analysis, we found that repellents were less effective against infected mosquitoes-marking an average 62% reduction in protective efficacy relative to uninfected mosquitoes (pooled odds ratio = 0.38, 95% confidence interval = 0.22-0.66; k = 96). Older infected mosquitoes were also more likely to show altered responses and loss of sensitivity to repellents, emphasizing the challenge of distinguishing between age or incubation period effects. Plasmodium- or Dengue-infected mosquitoes also did not show altered responses to repellents; however, Dengue-mosquito systems used inoculation practices that can introduce variability in repellency responses. Given our findings that repellents offer less protection against infected mosquitoes and that these vectors are the most dangerous in terms of disease transmission, then trials on repellent effectiveness should incorporate infected mosquitoes to improve predictability in blocking vector-human contact.

Relación del nivel socioeconómico con el rendimiento académico de estudiantes durante la pandemia por COVID-19 / Relationship of socioeconomic level with the academic performance of students during the COVID-19 pandemic

Introducción: el nivel socioeconómico (NSE) de las familias tiene un papel fundamentan en el desempeño académico de los estudiantes. Durante la pandemia, las familias con NSE bajo tuvieron menores oportunidades y se acrecentaron las desigualdades por limitaciones económicas y técnicas, lo cual pudo haber influido en las calificaciones y rendimiento académico de los alumnos. Objetivo: identificar la relación entre el NSE y el rendimiento académico de un grupo de estudiantes de licenciatura en enfermería durante la pandemia COVID-19. Metodología: estudio transversal, cuantitativo, analítico, con alumnos que tuvieron educación a distancia, se utilizó el instrumento denominado Nivel Socioeconómico (NSE) de la Asociación Mexicana de Agencias de Inteligencia de Mercado y Opinión Pública (AMAI), así como los promedios del semestre cursado en línea Resultados: participaron 167 alumnos, entre las variables de rendimiento académico y nivel socioeconómico se obtuvo un valor de p = 0.961, para las variables de sexo y estado civil se encontró asociación con un valor de p < 0.05. Conclusiones: no se identificó ninguna relación entre las variables del rendimiento académico y el nivel socioeconómico; sin embargo, otras variables como estado civil y sexo dieron significancia estadística, por lo que se sugiere ahondar en estas variables, así como su relación con el rendimiento académico.

Introduction: The socioeconomic level (SES) of families has a fundamental role in the academic performance of students, during the pandemic families with a low SES had fewer opportunities and increased inequalities due to economic and technical limitations, which could influence grades and academic performance. of the students Objective: To identify th e relationship between the SES and aca demic performance of nursing undergraduate students during COVID-19. Methodology: Cross-sectional, quantitative, analytical study with students who had distance education, the instrument called Socioeconomic Level (NSE) of the Mexican Association of Market Intelligence Agencies and Public Opinion (AMAI) was used. and the averages of the semester completed online. Results: 167 students participated, between the variables of academic performance and socioeconomic level a value of p = 0.961 was obtained, for the variables of sex, marital status an association was found with a p value less than 0.05. Conclusions: No relationship was identified between the variables of academic performance and socioeconomic level, however, other variables such as marital status and sex gave statistical significance, so it is suggested to delve into these variables as well as their relationship with academic performance.

Duplicación cráneo-facial (diprosopus) con trioftalmos diagnosticado mediante ecografía obstétrica 3D / Craniofacial duplication (diprosopus) with trioftalmos, diagnosed by 3D obstetric ultrasound

La duplicación cráneo-facial (diprosopus) es el resultado de la forma menos común de gemelos acoplados. La utilización de la ecografía 3D para el diagnóstico de esta patología ha sido reportada. Se presenta el segundo caso de esta patología en Colombia. Caso clínico de hijo de madre de 28 años a quien se le realizó diagnóstico prenatal con ecografía 3D, de duplicación craneofacial y de la columna vertebral. Cariotipo prenatal bandeo G: 46, XX. Al nacimiento se encontró feto de sexo femenino con duplicación craneofacial con la presencia de tres ojos, dos narices y dos bocas, con presencia de columna vertebral duplicada hasta la región cervical con espina bífida a nivel cervical. La utilización de ecografía 3D, permite realizar un diagnóstico oportuno de esta patología, lo que permite un abordaje multidisciplinario de las gestantes(AU)

Craniofacial duplication (diprosopus) is the result of the less common form of coupled twins. The use of 3D ultrasound for diagnosis of this disease has been reported.A second case of this disease occurs in Colombia. A clinical case of a son of 28-year-old mother, who underwent prenatal diagnosis with 3D ultrasound of craniofacial duplication and spine.Prenatal karyotype banding G: 46XX. At birth, a female fetus was found with craniofacial duplication, the presence of three eyes, two noses and two mouths, the presence of duplicate backbone up to the cervical region, and spina bifida at the cervical level. The use of 3D ultrasound allows early diagnosis of this disease, allowing a multidisciplinary approach of pregnant women(AU)

Groundwater protection strategies; a guide towards implementation

Guía para desarrollar e implementar estrategias de protección de las aguas subterráneas. Afirma que no pretende ser un manual riguroso puesto que cada país de la región necesita desenvolverse de acuerdo a sus políticas y a sus circunstancias locales. Señala los requerimientos y opciones para la protección de aguas subterráneas en cuatro aspectos: control de la explotación; zonificación del terreno en relación con la implementación de una política global de protección de los acuíferos y de definición de áreas especiales de protección alrededor de las captaciones de dicho recurso; control de fuentes puntuales de contaminación, tanto las existentes como las potencialmente nuevas; y control de de las fuentes dispersas de contaminación

Estrategias para la protección de aguas subterráneas; una guía para su implementación

Señala los requerimientos y opciones para la protección de aguas subterráneas en cuatro aspectos: control de la explotación; zonificación del terreno en relación con la implementación de una política global de protección de los acuíferos y de definición de áreas especiales de protección alrededor de las captaciones de aguas subterráneas; control de fuentes puntuales de contaminación, tanto las ya existentes como las nuevas potenciales, y control de fuentes dispersas de contaminación. En vista de la diversidad de la situación institucional y las disposiciones administrativas y legales existentes en cada país, no es posible presentar un modelo rígido para la protección de las aguas subterráneas