Bioinformatics Analysis of Human Papillomavirus 16 Integration in Cervical Cancer: Changes in MAGI-1 Expression in Premalignant Lesions and Invasive Carcinoma.

HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression.

WhatsApp-based intervention in urban Colombia to support the prevention of arboviral diseases: a feasibility study.

Arboviral diseases remain a significant health concern worldwide, with over half the world's population at risk for dengue alone. Without a vaccine or targeted treatment, the most effective strategy of prevention is vector management with community involvement. mHealth interventions, like WhatsApp, offer promising results for engaging communities and promoting healthier behaviors. This study explores the feasibility of integrating WhatsApp in vector control activities to improve arbovirus prevention in Colombia. A mixed-methods approach was employed to assess the WhatsApp-based intervention. WhatsApp messages were sent to 45 community women for 5 weeks to increase their knowledge and practices about dengue, Zika, and chikungunya. Pre-and-post surveys and focus group discussions were conducted in community settings to measure the feasibility and acceptability of this intervention. Chat reviews were done to assess the usability of users. A total of 1566 messages were exchanged in 45 WhatsApp chats. High acceptance and good usability (82% of users used the app for replying) were reported in this study. WhatsApp messages were perceived as short, clear, and enjoyable. Users liked the frequency, and design of messages. Pre- and post-surveys demonstrated improvements in the knowledge and practices of arboviral diseases. The intention to apply this knowledge in practice was reflected in a significant improvement, particularly in cleaning the laundry tank once a week (pre 62.1% to post 89.6%, p < 0.008). This study suggests that using WhatsApp as an additional tool could be a feasible, acceptable, and affordable strategy for improving the adoption of better practices in the prevention of arboviral diseases.

Benzo[a]pyrene promotes an epithelial-to-mesenchymal transition process in MCF10A cells and mammary tumor growth and brain metastasis in female mice.

Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA-MB-231 and MCF-7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.

Bisphenol A increases the size of primary mammary tumors and promotes metastasis in a murine model of breast cancer.

Triple negative breast cancer (TNBC) is a subtype of breast tumor characterized for the absence of estrogen and progesterone receptors expression and low HER2/neu expression. Bisphenol A (BPA) is an endocrine disrupting chemical with estrogenic activity that has been associated with increasing rates of breast cancer. Moreover, BPA is a solid organic synthetic chemical employed in the manufacture of many consumer products, epoxy resins and polycarbonate plastics including baby bottles, containers for food and beverages, and the lining of beverage cans. The G-protein-coupled estrogen receptor (GPER) is activated by endogenous hormones and synthetic ligands, such as BPA. GPER is expressed in TNBC cells and its expression is associated with larger tumor size, metastasis and worse survival prognosis. In breast cancer cells, BPA induces activation of signal transduction pathways that mediates migration and invasion via GPER in human TNBC MDA-MB-231 cells. In this study, we demonstrate that BPA induces an increase of GPER expression and its translocation from cytosol to cytoplasmic membrane, metalloproteinase (MMP)-2 and MMP-9 secretion, migration and invasion in murine TNBC 4T1 cells. In a murine TNBC model "in vivo" using 4T1 cells, BPA induces the formation of mammary tumors with more weight and volume, and an increase in the number of mice with metastasis to lung and nodules in lung compared with tumors and metastasis to lung of untreated Balb/cJ mice. In conclusion, our findings demonstrate that BPA mediates the growth of mammary primary tumors and metastasis to lung in a murine model of breast cancer.

COVID-19 Y su relación con factores sociodemográficos en la etapa pre-vacunatoria, provincia de Tucumán, Argentina, 2020-2021 / COVID-19 and its relationship with sociodemographic factors in the pre-vaccination period in Tucumán Province, Argentina, 2020-2021

RESUMEN INTRODUCCIÓN El impacto de COVID-19 en una población puede explicarse a través de los factores sociodemográficos y las respuestas de intervención. El objetivo fue evaluarlo en la provincia de Tucumán en la etapa previa a la vacunación. Se analizó la incidencia, letalidad y mortalidad de COVID-19 a nivel provincial y departamental, y se identificaron los factores sociodemográficos asociados. MÉTODOS Se realizó un estudio observacional de tipo ecológico con fuentes de datos secundarias en Tucumán. El período fue de marzo de 2020 a marzo de 2021. RESULTADOS Se registró una tasa de incidencia de COVID-19 de 4941 por 100 000 habitantes y una tasa de mortalidad de 93,29 por 100 000 habitantes. La incidencia de casos fue similar en varones y mujeres, y el grupo de 30 a 49 años presentó las tasas más altas. La tasa de mortalidad y letalidad en varones fue mayor que en mujeres, y en ambos sexos el grupo de 80 años o más presentó las mayores tasas. A nivel departamental, Capital, Tafí Viejo, Cruz Alta y Yerba Buena tuvieron las tasas de incidencia más altas. Burruyacú, Monteros y Trancas registraron las mayores tasas de mortalidad y letalidad. La incidencia de casos se vio afectada por la densidad poblacional y por el porcentaje de personas en hogares con alguna necesidad básica insatisfecha. DISCUSIÓN Se resalta la importancia de conocer la estructura, funcionalidad e identidad de las ciudades para comprender mejor su capacidad de resiliencia y adaptación frente a eventos como COVID-19.

ABSTRACT INTRODUCTION The population impact of COVID-19 can be explained by socio-demographic factors and the intervention responses. The objective was to evaluate it in the province of Tucumán in the pre-vaccination stage. Incidence, lethality and mortality of COVID-19 at province and department level were analyzed, identifying associated socio-demographic factors. METHODS An observational ecological study was conducted in Tucumán using secondary data sources. The period of study was from March 2020 to March 2021. RESULTS There was an incidence rate of COVID-19 of 4941 per 100000 inhabitants and a mortality rate of 93.29 per 100000 inhabitants. The incidence of cases was similar among males and females, and the age group between 30 and 49 years showed the highest rates. Mortality and lethality were higher in men than in women, and in both sexes the age group of 80 years and over presented the highest rates. At department level, Capital, Tafí Viejo, Cruz Alta and Yerba Buena had the highest incidence rates. Burruyacú, Monteros and Trancas had the highest mortality and lethality rates. The incidence of cases was affected by population density and by the percentage of people living in households with an unsatisfied basic need. DISCUSSION This work highlights the importance of knowing the structure, functionality and identity of cities to better understand their resilience and adaptation capacity in the face of events such as COVID-19.

Dynamic state of plasmid genomic architectures resulting from XerC/D-mediated site-specific recombination in Acinetobacter baumannii Rep_3 superfamily resistance plasmids carrying blaOXA-58 - and TnaphA6-resistance modules.

The acquisition of bla OXA genes encoding different carbapenem-hydrolyzing class-D ß-lactamases (CHDL) represents a main determinant of carbapenem resistance in the nosocomial pathogen Acinetobacter baumannii. The blaOXA-58 gene, in particular, is generally embedded in similar resistance modules (RM) carried by plasmids unique to the Acinetobacter genus lacking self-transferability. The ample variations in the immediate genomic contexts in which blaOXA-58 -containing RMs are inserted among these plasmids, and the almost invariable presence at their borders of non-identical 28-bp sequences potentially recognized by the host XerC and XerD tyrosine recombinases (pXerC/D-like sites), suggested an involvement of these sites in the lateral mobilization of the gene structures they encircle. However, whether and how these pXerC/D sites participate in this process is only beginning to be understood. Here, we used a series of experimental approaches to analyze the contribution of pXerC/D-mediated site-specific recombination to the generation of structural diversity between resistance plasmids carrying pXerC/D-bounded bla OXA-58- and TnaphA6-containing RM harbored by two phylogenetically- and epidemiologically-closely related A. baumannii strains of our collection, Ab242 and Ab825, during adaptation to the hospital environment. Our analysis disclosed the existence of different bona fide pairs of recombinationally-active pXerC/D sites in these plasmids, some mediating reversible intramolecular inversions and others reversible plasmid fusions/resolutions. All of the identified recombinationally-active pairs shared identical GGTGTA sequences at the cr spacer separating the XerC- and XerD-binding regions. The fusion of two Ab825 plasmids mediated by a pair of recombinationally-active pXerC/D sites displaying sequence differences at the cr spacer could be inferred on the basis of sequence comparison analysis, but no evidence of reversibility could be obtained in this case. The reversible plasmid genome rearrangements mediated by recombinationally-active pairs of pXerC/D sites reported here probably represents an ancient mechanism of generating structural diversity in the Acinetobacter plasmid pool. This recursive process could facilitate a rapid adaptation of an eventual bacterial host to changing environments, and has certainly contributed to the evolution of Acinetobacter plasmids and the capture and dissemination of bla OXA-58 genes among Acinetobacter and non-Acinetobacter populations co-residing in the hospital niche.

Applicability of the Mexican ovitrap system for Aedes vector surveillance in Colombia.

Ovitraps can detect Aedes vectors at an early stage and can serve as an alarm indicator for outbreak prediction. This study aimed to summarize the available literature about the ovitrap system and to determine its feasibility, required resources and costs when installing and maintaining this vector surveillance system in the municipality of Los Patios, Colombia. A scoping review to assess the role of ovitraps as a tool for Aedes vector surveillance was conducted. The subsequent fieldwork consisted of mapping the municipality, manufacturing, and installing 40 ovitraps in 10 blocks, revising them weekly for 4 weeks by two half-time employed vector control technicians, and carrying out a cost analysis. A total of 38 studies were included in this review showing that ovitraps had a better performance than other entomological surveillance methods and a positive correlation with other entomological and disease variables. From the field results over 4 weeks, a high proportion of positive ovitraps (80%, 90%, 75%, 97.5%) and positive blocks (100%) as well as a good acceptance by house owners (76.9%), were identified. Operational indicators such as average installation time of the ovitraps (10h15 m), weekly reading and reinstallation (on average 7h27 m) and the cost of the intervention (COL$1,142,304.47/US$297) were calculated. Literature shows that ovitraps are sensitive to detect the presence of Aedes mosquitoes, providing data efficiently and timely for outbreak prediction. The field testing showed it is an affordable and feasible method in the context of a Colombian municipality and similar endemic areas.

Caveolae Microdomains Mediate STAT5 Signaling Induced by Insulin in MCF-7 Breast Cancer Cells.

Caveolae are small plasma membrane invaginations constituted for membrane proteins namely caveolins and cytosolic proteins termed cavins, which can occupy up to 50% of the surface of mammalian cells. The caveolae have been involved with a variety of cellular processes including regulation of cellular signaling. Insulin is a hormone that mediates a variety of physiological processes through activation of insulin receptor (IR), which is a tyrosine kinase receptor expressed in all mammalian tissues. Insulin induces activation of signal transducers and activators of transcription (STAT) family members including STAT5. In this study, we demonstrate, for the first time, that insulin induces phosphorylation of STAT5 at tyrosine-694 (STAT5-Tyr(P)694), STAT5 nuclear accumulation and an increase in STAT5-DNA complex formation in MCF-7 breast cancer cells. Insulin also induces nuclear accumulation of STAT5-Tyr(P)694, caveolin-1, and IR in MCF-7 cells. STAT5 nuclear accumulation and the increase of STAT5-DNA complex formation require the integrity of caveolae and microtubule network. Moreover, insulin induces an increase and nuclear accumulation of STAT5-Tyr(P)694 in MDA-MB-231 breast cancer cells. In conclusion, results demonstrate that caveolae and microtubule network play an important role in STAT5-Tyr(P)694, STAT5 nuclear accumulation and STAT5-DNA complex formation induced by insulin in breast cancer cells.

Crisis de reparación: brechas y gestión del cuidado en niños, niñas y adolescentes institucionalizados(as) / Reparation crisis: gaps and care management in institutionalized children and adolescents

INTRODUCCIÓN: La institucionalización de niños, niñas y adolescentes (NNA) es una medida frecuente en el país, pese a que la evidencia es contundente en señalar las graves consecuencias a nivel global en NNA bajo este régimen de cuidado, destacando el rezago en el desarrollo y problemas de salud mental. En este escenario, los enfermeros(as) de los equipos de Salud Mental comunitaria participan en su tratamiento y rehabilitación. OBJETIVO: Develar la gestión del cuidado en el trabajo con NNA pertenecientes a residencias Mejor Niñez, adscritos a Centros de Salud Mental, con enfoque comunitario. METODOLOGÍA: Se trabaja bajo el paradigma cualitativo, con análisis de contenido, en una población de enfermeros(as) adscritos a centros de Salud Mental, seleccionados por muestreo deliberado. Investigación autorizada por el Comité Ético-Científico de Valdivia (Chile). RESULTADOS: Se obtuvieron dos metacategorías: La gestión del cuidado de enfermeros(as) de Salud Mental en NNA institucionalizados(as), que engloba el actuar de enfermería según las realidades locales, y las brechas y nodos de las residencias Mejor Niñez: Crisis de reparación, que incluye narrativas de dilemas éticos y de coordinación. CONCLUSIONES: Existen falencias respecto del bienestar y seguridad de los niños(as) institucionalizados(as), lo cual puede generar consecuencias nocivas en el proceso de reparación. Se sugiere la incorporación de enfermeros(as) al staff de hogares institucionales, así como el empleo de protocolos de acción para el abordaje de enfermería en salud mental dirigido a esta población.

INTRODUCTION: Institutionalization of children and adolescents (NNA) is a frequent measure in the country, though the evidence is conclusive identifying the serious consequences at a general level in children and adolescents under this care regime, especially in evelopmental problems and terms of mental health conditions. In this scenario, nurses from community mental health teams participate in the treatment and rehabilitation of these users. The purpose is to generate knowledge about care management and the challenges related to this context. METHODOLOGY: The population consisted of nurses from Mental Health centers in the South of Chile, selected by means of a non-probabilistic deliberate sampling and snowball technique. This research was authorized by the Valdivia's Ethical-Scientific Committee(Chile). RESULTS: Two meta-categories were obtained: The care management of Mental Health nurses for institutionalized children and adolescents, which includes nursing actions according to the realities of each locality; and the second meta-category is called "Mejor Niñez" residencies Gaps and nodes: Crisis of reparation, which includes accounts of ethical and coordination dilemmas. CONCLUSIONES: There are still flaws regarding the safety and well-being of institutionalized children, which may generate harmful consequences in the reparation process. The incorporation of nurses to the staff of institutional homes is suggested, as well as the use of action protocols for the mental healthnursingapproach aimed at this population.

Beyond SARS-CoV-2: epidemiological surveillance of respiratory viruses in Jalisco, Mexico.

Introduction: Respiratory viral infections represent a significant global health burden. Historically, influenza, rhinovirus, respiratory syncytial virus, and adenovirus have been the prevalent viruses; however, the landscape shifted with the widespread emergence of SARS-CoV-2. The aim of this study is to present a comprehensive epidemiological analysis of viral respiratory infections in Jalisco, Mexico. Methods: Data encompassing individuals with flu-like symptoms from July 2021 to February 2023 was scrutinized for viral diagnosis through PCR multiplex. The effect of social mobility on the increase in respiratory viral diagnosis infection was considered to estimate its impact. Additionally, sequences of respiratory viruses stored in public databases were retrieved to ascertain the phylogenetic classification of previously reported viruses in Mexico. Results: SARS-CoV-2 was the most detected virus (n = 5,703; 92.2%), followed by influenza (n = 479; 7.78%). These viruses were also found as the most common co-infection (n = 11; 50%), and for those with influenza, a higher incidence of severe disease was reported (n = 122; 90.4%; p < 0.001). Regarding comorbidities and unhealthy habits, smoking was found to be a risk factor for influenza infection but a protective factor for SARS-CoV-2 (OR = 2.62; IC 95%: 1.66-4.13; OR = 0.65; IC 95%: 0.45-0.94), respectively. Furthermore, our findings revealed a direct correlation between mobility and the prevalence of influenza infection (0.214; p < 0.001). Discussion: The study presents evidence of respiratory virus reemergence and prevalence during the social reactivation, facilitating future preventive measures.

Cancer-associated Fibroblasts Communicate with Breast Tumor Cells Through Extracellular Vesicles in Tumor Development.

Breast cancer is the leading cause of cancer death among women worldwide. In solid tumors, the microenvironment plays a critical role in tumor development, and it has been described a communication between the different cell types that conform the stroma, including fibroblasts, pericytes, adipocytes, immune cells and cancer-associated fibroblasts. Intercellular communication is bidirectional, complex, multifactorial and is mediated by the secretion of molecules and extracellular vesicles. The extracellular vesicles are vesicles limited by two membranes that are secreted by normal and cancer cells into the extracellular space. Extracellular vesicle cargo is complex and includes proteins, miRNAs, DNA and lipids, and their composition is specific to their parent cells. Extracellular vesicles are taken up for neighboring or distant cells. Particularly, extracellular vesicles from breast cancer cells are taken up for fibroblasts and it induces the activation of fibroblasts into cancer-associated fibroblasts. Interestingly, cancer associated fibroblasts release extracellular vesicles that are taken up for breast cancer cells and promote migration, invasion, proliferation, epithelial-mesenchymal transition, changes in metabolism, chemoresistance, evasion of immune system and remodeling of extracellular matrix. In addition, the enrichment of specific cargos in extracellular vesicles of breast cancer patients has been suggested to be used as biomarkers of the disease. Here we review the current literature about the intercommunication between tumor cells and cancer associated fibroblasts through extracellular vesicles in breast cancer.

Dp71 Point Mutations Induce Protein Aggregation, Loss of Nuclear Lamina Integrity and Impaired Braf35 and Ibraf Function in Neuronal Cells.

Dystrophin Dp71 is the most abundant product of the Duchenne muscular dystrophy gene in the nervous system, and mutations impairing its function have been associated with the neurodevelopmental symptoms present in a third of DMD patients. Dp71 is required for the clustering of neurotransmitter receptors and the neuronal differentiation of cultured cells; nonetheless, its precise role in neuronal cells remains to be poorly understood. In this study, we analyzed the effect of two pathogenic DMD gene point mutations on the Dp71 function in neurons. We engineered C272Y and E299del mutations to express GFP-tagged Dp71 protein variants in N1E-115 and SH-SY5Y neuronal cells. Unexpectedly, the ectopic expression of Dp71 mutants resulted in protein aggregation, which may be mechanistically caused by the effect of the mutations on Dp71 structure, as predicted by protein modeling and molecular dynamics simulations. Interestingly, Dp71 mutant variants acquired a dominant negative function that, in turn, dramatically impaired the distribution of different Dp71 protein partners, including ß-dystroglycan, nuclear lamins A/C and B1, the high-mobility group (HMG)-containing protein (BRAF35) and the BRAF35-family-member inhibitor of BRAF35 (iBRAF). Further analysis of Dp71 mutants provided evidence showing a role for Dp71 in modulating both heterochromatin marker H3K9me2 organization and the neuronal genes' expression, via its interaction with iBRAF and BRAF5.

An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

Expression of obesity- and type-2 diabetes-associated genes in omental adipose tissue of individuals with obesity.

AIMS: Obesity and type 2 diabetes mellitus are two pathologies that share metabolic abnormalities in most of the cases; however, there are differences as well. Some studies have reported that approximately 30% of obese patients have normal glucose and lipid levels in blood despite an accumulation of abdominal adipose tissue. Here, we compare the gene expression in adipose tissue of several genes associated with obesity and/or diabetes between obese patients without T2D and obese patients with T2D. METHODS: Omental adipose tissue was collected during the patients elective bariatric surgery. Gene expression was determined by real-time PCR. Phenotypic variables were correlated with gene expression and 2^-ΔΔCt relative expression analysis between groups was performed. RESULTS: The stronger correlations in the obese without T2D or reference group was between ICAM1 and HbA1c; HP and TC and LDL while in the obese with diabetes or case group the correlation occurred between CSF1 and BMI. A correlation between HP and TC was found in the case group as well. The expression of VEGFA, CCND2, IL1R1 and PTEN was downregulated in the obese with T2D group. CONCLUSIONS: This study identified genes whose expression is different between obese subjects with and without diabetes. Those genes are related to inflammation, cholesterol transport, adipocyte differentiation/expansion and browning.

RNA Foci Formation in a Retinal Glial Model for Spinocerebellar Ataxia Type 7.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by cerebellar ataxia and retinopathy. SCA7 is caused by a CAG expansion in the ATXN7 gene, which results in an extended polyglutamine (polyQ) tract in the encoded protein, the ataxin-7. PolyQ expanded ataxin-7 elicits neurodegeneration in cerebellar Purkinje cells, however, its impact on the SCA7-associated retinopathy remains to be addressed. Since Müller glial cells play an essential role in retinal homeostasis, we generate an inducible model for SCA7, based on the glial Müller MIO-M1 cell line. The SCA7 pathogenesis has been explained by a protein gain-of-function mechanism, however, the contribution of the mutant RNA to the disease cannot be excluded. In this direction, we found nuclear and cytoplasmic foci containing mutant RNA accompanied by subtle alternative splicing defects in MIO-M1 cells. RNA foci were also observed in cells from different lineages, including peripheral mononuclear leukocytes derived from SCA7 patient, suggesting that this molecular mark could be used as a blood biomarker for SCA7. Collectively, our data showed that our glial cell model exhibits the molecular features of SCA7, which makes it a suitable model to study the RNA toxicity mechanisms, as well as to explore therapeutic strategies aiming to alleviate glial dysfunction.

RT-qPCR Assays for Rapid Detection of the N501Y, 69-70del, K417N, and E484K SARS-CoV-2 Mutations: A Screening Strategy to Identify Variants With Clinical Impact.

Background: Several variants of the SARS-CoV-2 have been documented globally during the current COVID-19 pandemic. The N501Y, 69-70del, K417N, and E484K SARS-CoV-2 mutations have been documented among the most relevant due to their potential pathogenic biological effects. This study aimed to design, validate, and propose a fast real-time RT-qPCR assay to detect SARS-CoV-2 mutations with possible clinical and epidemiological relevance in the Mexican population. Methods: Targeting spike (S) gene mutations of SARS-CoV-2 (N501Y, 69-70del, K417N, and E484K), specific primers, and probes for three specific quantitative reverse transcription PCR (RT-qPCR) assays were designed, and validated using Sanger sequencing. These assays were applied in clinical samples of 1060 COVID-19 patients from Jalisco Mexico. Results: In silico analyzes showed high specificity of the three assays. Amplicons of samples were confirmed through sequencing. The screening of samples of COVID-19 patients allowed the identification of the E484K mutation in nine individuals and the identification of P.2 Brazilian variant in Mexico. Conclusion: This work provides low-cost RT-qPCR assays for rapid screening and molecular surveillance of mutations with potential clinical impact. This strategy allowed the detection of E484K mutation and P.2 variant for the first time in samples from the Mexican population.

Deciphering the epigenetic network in cancer radioresistance.

Radiotherapy, in addition to surgery and systemic chemotherapy, remains the core of the current clinical management of cancer. Radioresistance is one of the major causes of disease progression and mortality in cancer; therefore, it is a significant challenge in the treatment of locally advanced, recurrent and metastatic cancer. Epigenetic mechanisms that control hallmarks of cancer have a key role in the development of radiation resistance of cancer cells. Recent advances in DNA methylation, histone modification, chromatin remodeling and non-coding RNAs identified in the control of signal transduction pathways in cancer and cancer stem cells have provided even greater promise in the improvement of understanding cancer radioresistance. Many epigenetic drugs that target epigenetic enzymes revert the radioresistant phenotypes decreasing the possibility that resistant cancer cells will develop refractory tumors to radiotherapy. Epigenetic profiles identified as regulators of DNA damage repair, hypoxia, cell survival, apoptosis and invasion are determinants in the development of tumor radioresistance; hence, they also are promising in personalized medicine to develop novel targeted therapies or biomarkers to follow-up the effectiveness of radiotherapy. Now, it is clear that radiotherapy can influence a complex epigenetic network for transcriptional reprogramming, enabling the cells to adapt and avoid the effect of radiotherapy. This review aims to highlight the epigenetic modifications identified in cancer radioresistance and to discuss approaches to disable epigenetic networks to increase the sensitivity and specificity of radiotherapy.

Transcriptome Analysis Reveals Altered Inflammatory Pathway in an Inducible Glial Cell Model of Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1), the most frequent inherited muscular dystrophy in adults, is caused by the CTG repeat expansion in the 3'UTR of the DMPK gene. Mutant DMPK RNA accumulates in nuclear foci altering diverse cellular functions including alternative splicing regulation. DM1 is a multisystemic condition, with debilitating central nervous system alterations. Although a defective neuroglia communication has been described as a contributor of the brain pathology in DM1, the specific cellular and molecular events potentially affected in glia cells have not been totally recognized. Thus, to study the effects of DM1 mutation on glial physiology, in this work, we have established an inducible DM1 model derived from the MIO-M1 cell line expressing 648 CUG repeats. This new model recreated the molecular hallmarks of DM1 elicited by a toxic RNA gain-of-function mechanism: accumulation of RNA foci colocalized with MBNL proteins and dysregulation of alternative splicing. By applying a microarray whole-transcriptome approach, we identified several gene changes associated with DM1 mutation in MIO-M1 cells, including the immune mediators CXCL10, CCL5, CXCL8, TNFAIP3, and TNFRSF9, as well as the microRNAs miR-222, miR-448, among others, as potential regulators. A gene ontology enrichment analyses revealed that inflammation and immune response emerged as major cellular deregulated processes in the MIO-M1 DM1 cells. Our findings indicate the involvement of an altered immune response in glia cells, opening new windows for the study of glia as potential contributor of the CNS symptoms in DM1.

Asociación entre incidencia de varicela y variabilidad climática en la provincia de Tucumán, Argentina, 2005-2019 / Association between varicella incidence and climate variability in Tucumán province, Argentina, 2005-2019

INTRODUCTION: Varicella is a vaccine-preventable disease with marked seasonality. Few studies incorporate climatic variables to understand the epidemiological characteristics of this disease. The aim was to evaluate the relationship between varicella incidence and climatic variables in Tucumán (a province with temperate subtropical climate) during 2005-2019. METHODS: The relationship in pre- (2005-2014) and post-vaccination (2015-2019) periods was analyzed, identifying the associated climatic variables and the cut-off point where the risk of transmission increased. An observational ecological study was carried out with secondary data sources. R software was used. The information was split into three time series: 2005-2009, 2010-2014 and 2015-2019. For each period, a description of the time series was performed and generalized additive models (GAMs) were built using a negative binomial distribution. RESULTS: A seasonal behavior was observed, with peak incidence during spring in all periods. In the post-vaccination period, the peak occurred later (epidemiological week [EW] 46) than in the pre-vaccination periods (EW 43 and 42). Maximum temperature and relative humidity were associated during the first two periods, while minimum temperature, wind and thermal amplitude were associated in the third one. DISCUSSION: This study helped establish the relationship between climatic variables and varicella in Tucumán.

Pubertad precoz periférica / Peripheral precocious puberty

Introducción: El síndrome de Mc Cune-Albright (SMA) es una rara entidad asociada con la displasia fibrosa poliostótica, con la presencia de manchas de color café con leche y también con la hiperfunción endocrina. La alteración hormonal más frecuente es la pubertad precoz. El SMA se debe a mutaciones activadoras del gen GNAS1. Objetivo: Describir las características clínicas de una paciente con síndrome de Mc Cune-Albright con una pubertad precoz. Métodos: Se realizó una revisión de la historia clínica como fuente primaria y fueron incorporados todos los elementos clínicos, bioquímicos, imagenológicos y genéticos que conformaron la valoración integral de la paciente. Presentación de caso: Se presenta un caso poco frecuente de síndrome de Mc Cune-Albright en una niña de siete años de edad con mamas Tanner II-III, sangrado vaginal, vello axilar y pubiano escaso, manchas café con leche y lesiones óseas. Lleva tratamiento con tamoxifeno, lo que ha logrado mantener frenada la progresión del desarrollo puberal. Conclusiones: Aunque esta entidad es de carácter benigno y la prevalencia es extremadamente baja, el inicio puberal precoz y el compromiso de la talla final pueden producir impacto psicológico en la calidad de vida y en el desarrollo normal del individuo(AU)

Introduction: Mc Cune-Albright syndrome (SMA, by its acronym in Spanish) is a rare entity associated with polyostotic fibrous dysplasia, with the presence of brown spots with milk and also with endocrine hyperfunction. The most common hormonal alteration is precocious puberty. SMA is caused by GNAS1 gene´s activator mutations. Objective: Describe the clinical characteristics of a patient with Mc Cune-Albright syndrome with precocious puberty. Methods: A review of the medical history was carried out as a primary source and all the clinical, biochemical, imaging and genetic elements that made up the comprehensive assessment of the patient were incorporated. Case presentation: A rare case of Mc Cune-Albright syndrome occurs in a seven-year-old girl with Tanner II-III breasts, vaginal bleeding, axillary and pubic hair, brown spots with milk and bone lesions. She is treated with tamoxifen, which has managed to keep the progression of pubertal development slow. Conclusions: Although this entity is benign in nature and the prevalence is extremely low, early pubertal onset and the compromise of the final size can have a psychological impact on the quality of life and normal development of the individual(AU)