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SARS-CoV-2 Mu variant emerged in Colombia in 2021 and spread globally. In 49 serum samples from vaccinees and COVID-19 survivors in Colombia, neutralization was significantly lower (p<0.0001) for Mu than a parental strain and variants of concern. Only the Omicron variant of concern demonstrated higher immune evasion.
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COVID-19 , Vacinas Virais , Humanos , Imunidade , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
BACKGROUND: Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. METHODS: Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn's Multiple Comparison and T tests. Kaplan-Meier and log-rank tests were used to determine overall survival. RESULTS: Gal-7 was constantly downregulated in our meta-analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. CONCLUSIONS: Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks, such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.
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Galectinas/metabolismo , Microambiente Tumoral/fisiologia , Neoplasias do Colo do Útero/metabolismo , Feminino , Humanos , Neoplasias do Colo do Útero/patologiaRESUMO
According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration.
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Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA/genética , Neoplasias do Colo do Útero/genética , Proteínas Wnt/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Meios de Cultivo Condicionados/farmacologia , Feminino , Células HeLa , Humanos , Interferência de RNA , RNA Interferente Pequeno , Proteínas Recombinantes/farmacologia , Neoplasias do Colo do Útero/metabolismo , Proteínas Wnt/biossíntese , Proteínas Wnt/farmacologia , Via de Sinalização Wnt/genéticaRESUMO
Infections with high-risk human papillomaviruses (HPVs) are causally involved in the development of anogenital cancer. HPVs apparently evade the innate immune response of their host cells by dysregulating immunomodulatory factors such as cytokines and chemokines, thereby creating a microenvironment that favors malignancy. One central key player in the immune surveillance interactome is interleukin-1 beta (IL-1ß) which not only mediates inflammation, but also links innate and adaptive immunity. Because of its pleiotropic physiological effects, IL-1ß production is tightly controlled on transcriptional, post-translational and secretory levels. Here, we describe a novel mechanism how the high-risk HPV16 E6 oncoprotein abrogates IL-1ß processing and secretion in a NALP3 inflammasome-independent manner. We analyzed IL-1ß regulation in immortalized keratinocytes that harbor the HPV16 E6 and/or E7 oncogenes as well as HPV-positive cervical tumor cells. While in primary and in E7-immortalized human keratinocytes the secretion of IL-1ß was highly inducible upon inflammasome activation, E6-positive cells did not respond. Western blot analyses revealed a strong reduction of basal intracellular levels of pro-IL-1ß that was independent of dysregulation of the NALP3 inflammasome, autophagy or lysosomal activity. Instead, we demonstrate that pro-IL-1ß is degraded in a proteasome-dependent manner in E6-positive cells which is mediated via the ubiquitin ligase E6-AP and p53. Conversely, in E6- and E6/E7-immortalized cells pro-IL-1ß levels were restored by siRNA knock-down of E6-AP and simultaneous recovery of functional p53. In the context of HPV-induced carcinogenesis, these data suggest a novel post-translational mechanism of pro-IL-1ß regulation which ultimately inhibits the secretion of IL-1ß in virus-infected keratinocytes. The clinical relevance of our results was further confirmed in HPV-positive tissue samples, where a gradual decrease of IL-1ß towards cervical cancer could be discerned. Hence, attenuation of IL-1ß by the HPV16 E6 oncoprotein in immortalized cells is apparently a crucial step in viral immune evasion and initiation of malignancy.
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Transformação Celular Viral/imunologia , Papillomavirus Humano 16/imunologia , Imunidade Inata , Interleucina-1beta/imunologia , Proteínas Oncogênicas Virais/imunologia , Processamento de Proteína Pós-Traducional/imunologia , Proteólise , Proteínas Repressoras/imunologia , Evasão Tumoral/imunologia , Proteína Supressora de Tumor p53/imunologia , Ubiquitina-Proteína Ligases/imunologia , Linhagem Celular Transformada , Transformação Celular Viral/genética , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Processamento de Proteína Pós-Traducional/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Evasão Tumoral/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Background/Objectives: Preterm birth (PTB) remains a significant global health challenge. Previous attempts to predict preterm birth in the first trimester using cervical length have been contradictory. The cervical consistency index (CCI) was introduced to quantify early cervical changes and has shown promise across various clinical scenarios in the mid-trimester, though testing in the first trimester is lacking. This study aims to assess the cervical consistency index performance in predicting preterm birth during the first trimester of pregnancy. Methods: In this prospective cohort study, focused exclusively on research, women with singleton pregnancies, both with and without a history of spontaneous preterm birth (sPTB), were included. The primary outcome was sPTB before 37 weeks, with a secondary outcome of sPTB before 34 weeks. CCI measurements were taken between 11+0 to 13+6 weeks of gestation. Receiver operating characteristic (ROC) curves were generated, and sensitivity and specificity were calculated for the optimal cut-off and for the 5th, 10th, and 15th percentile. Intraobserver and interobserver agreements were assessed using the intraclass correlation coefficient (ICC). Results: Among the 667 patients analyzed, the rates of sPTB before 37 and 34 weeks were 9.2% (61/667) and 1.8% (12/667), respectively. The detection rates (DRs) for CCI predicting PTB before 37 and 34 weeks were 19.7% (12/61) and 33.3% (4/12). Negative predictive values were 91.8% (546/595) and 98.7% (588/596), while the areas under the curve (AUC) for sPTB before 37 and 34 weeks were 0.62 (95% CI: 0.54-0.69) and 0.80 (95% CI: 0.71-0.89), respectively. Of the 61 patients with preterm birth, 13 (21.3%) had a preterm birth history; in this group, the CCI percentile 10th identified 39% (5/13). Intraobserver ICC was 0.862 (95% CI: 0.769-0.920), and interobserver ICC was 0.833 (95% CI: 0.722-0.902). Conclusions: This study suggests that utilizing CCI in the first trimester of pregnancy could serve as a valuable tool for predicting preterm birth before 34 weeks of gestation, demonstrating robust intraobserver and interobserver reliability.
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PURPOSE: Preterm birth (PTB) is a public health issue. Interventions to prolong the length of gestation have not achieved the expected results, as the selection of population at risk of PTB is still a challenge. Cervical length (CL) is the most accepted biomarker, however in the best scenario the CL identifies half of the patients. It is unlikely that a single measure identifies all pregnant women who will deliver before 37 weeks of gestation, considering the multiple pathways theory. We planned this cohort to study the link between the vaginal microbiome, the proteome, metabolome candidates, characteristics of the cervix and the PTB. PARTICIPANTS: Pregnant women in the first trimester of a singleton pregnancy are invited to participate in the study. We are collecting biological samples, including vaginal fluid and blood from every patient, also performing ultrasound measurement that includes Consistency Cervical Index (CCI) and CL. The main outcome is the delivery of a neonate before 37 weeks of gestation. FINDINGS TO DATE: We have recruited 244 pregnant women. They all have measurements of the CL and CCI. A vaginal sample for microbiome analysis has been collected in the 244 patients. Most of them agreed to blood collection, 216 (89%). By August 2021, 100 participants had already delivered. Eleven participants (11 %) had a spontaneous PTB. FUTURE PLANS: A reference value chart for the first trimester CCI will be created. We will gather information regarding the feasibility, reproducibility and limitations of CCI. Proteomic and metabolomic analyses will be done to identify the best candidates, and we will validate their use as predictors. Finally, we plan to integrate clinical data, ultrasound measurements and biological profiles into an algorithm to obtain a multidimensional biomarker to identify the individual risk for PTB.
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Microbiota , Nascimento Prematuro , Biomarcadores , Colo do Útero/diagnóstico por imagem , Colômbia , Feminino , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Proteômica , Reprodutibilidade dos TestesRESUMO
Human Vgamma9Vdelta2 T cells are characterized by a unique specificity for certain tumors (e.g., Daudi), cells presenting so-called phosphoantigens such as isopentenyl pyrophosphate (IPP), or cells treated with aminobisphosphonates. We now report conversion of hematopoietic and nonhematopoietic tumor cell lines into Vgamma9Vdelta2 T cell activators by means of short hairpin RNA-mediated knockdown of expression of the IPP-consuming enzyme, farnesyl pyrophosphate synthase (FPPS). FPPS knockdown cells activated Vgamma9Vdelta2 T cells, as measured by increased levels of CD69 and CD107a, killing of FPPS knockdown cells, and induction of IFN-gamma secretion. The IPP-synthesis-inhibiting drug mevastatin reduced Vgamma9Vdelta2 T cell activation by FPPS knockdown cells but not activation by the phosphoantigen bromohydrin pyrophosphate. In conclusion, our data support the concept of Vgamma9Vdelta2 T cells as sensors of a dysregulated isoprenoid metabolism and suggest therapeutic down-modulation of FPPS expression as an additional tool to target tumor cells to Vgamma9Vdelta2 T cell-mediated immunosurveillance.
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Dimetilaliltranstransferase/metabolismo , Ácido Mevalônico/farmacologia , Neoplasias/enzimologia , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/enzimologia , Linfócitos T/imunologia , Linhagem Celular , Dimetilaliltranstransferase/genética , Regulação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/genética , Hematopoese , Humanos , Ativação Linfocitária/imunologia , Transdução de Sinais/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
In this study, changes in the electrochemical conditions of oil fields caused by biofilms with sulfate-reducing bacteria have been studied as they promote localized pitting damage, reservoir souring problems, and many other processes including well plugging that lead to increased production costs. Biofilm formation and its effects on 1020 carbon steel surfaces were evaluated in a discontinuous electrochemical reactor by using a bacterial consortium isolated from the injection water of a Colombian oil field. Sulfide concentration and pH values were observed to decrease, which was consistent with the exponential planktonic sulfate-reducing bacterial growth. The formation of a biofilm that adheres to a porous layer of corrosion products was identified using scanning electron microscopy and energy-dispersive X-ray spectroscopy. The morphology of the films revealed the presence of the biofilm and corrosion product crystals. Open circuit potential presented a negative shift in the potential during the first 24 h in a biotic cell. Electrochemical impedance spectroscopy showed a change in the behavior of the resistive zone for both systems, a charge transfer trend in the abiotic cell, and a transformation of the charge transfer process to a diffusive process in the biotic cell after 48 h. The polarization resistance showed its lowest resistivity 74.95 Ω·cm-2 during the first 48 h, while the corrosion rate was estimated as 3.37 mpy. This research contributes to the understanding of corrosion mechanisms in the metal-solution interface via detailed monitoring of biofilm growth.
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Biofilmes , Carbono/química , Técnicas Eletroquímicas/métodos , Microscopia Eletrônica de Varredura/métodos , Aço/química , Corrosão , Reprodutibilidade dos Testes , Espectrometria por Raios X , ÁguaRESUMO
BACKGROUND: Our previous studies showed that the expression of the monocyte-chemoattractant protein (MCP)-1, a chemokine, which triggers the infiltration and activation of cells of the monocyte-macrophage lineage, is abrogated in human papillomavirus (HPV)-positive premalignant and malignant cells. In silico analysis of the MCP-1 upstream region proposed a putative p53 binding side about 2.5 kb upstream of the transcriptional start. The aim of this study is to monitor a physiological role of p53 in this process. RESULTS: The proposed p53 binding side could be confirmed in vitro by electrophoretic-mobility-shift assays and in vivo by chromatin immunoprecipitation. Moreover, the availability of p53 is apparently important for chemokine regulation, since TNF-alpha can induce MCP-1 only in human keratinocytes expressing the viral oncoprotein E7, but not in HPV16 E6 positive cells, where p53 becomes degraded. A general physiological role of p53 in MCP-1 regulation was further substantiated in HPV-negative cells harboring a temperature-sensitive mutant of p53 and in Li-Fraumeni cells, carrying a germ-line mutation of p53. In both cases, non-functional p53 leads to diminished MCP-1 transcription upon TNF-alpha treatment. In addition, siRNA directed against p53 decreased MCP-1 transcription after TNF-alpha addition, directly confirming a crosstalk between p53 and MCP-1. CONCLUSION: These data support the concept that p53 inactivation during carcinogenesis also affects immune surveillance by interfering with chemokine expression and in turn communication with cells of the immunological compartment.
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Transformação Celular Neoplásica/genética , Quimiocina CCL2/genética , Regulação da Expressão Gênica , Proteína Supressora de Tumor p53/genética , Northern Blotting , Western Blotting , Linhagem Celular , Transformação Celular Neoplásica/imunologia , Quimiocina CCL2/biossíntese , Imunoprecipitação da Cromatina , Eletroforese em Gel de Poliacrilamida , Ensaio de Desvio de Mobilidade Eletroforética , Elementos Facilitadores Genéticos/genética , Humanos , Queratinócitos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
INTRODUCTION: Human papillomavirus molecular detection prevents cervical cancer (CC). To widen its use, cervical-vaginal self-collection devices are proposed. Our aim was to determine the acceptability of self-sampled cervical-vaginal protocol and the reproducibility of results using HPV detection brushes in a low-income Colombian population between 35 and 65 years old. METHODS: Cross-sectional study including women classified as medium to high-risk for developing CC by using a short-standardized survey. After receiving instructions, women self-collected a cervical-vaginal sample. Subsequently, a perception survey was conducted. RESULTS: Four hundred and twenty-three women performed self-collected sampling. The median age was 46.5 years (IQR 40-52), 56.5% were housewives, and 55.1% had finished elementary school. About 99% of the population (n=419) considered that they understood the instructions, 19.4% (n=82) reported having concerns about the self-collected sample, 9.2% (n=39) distrusted the results because of the self-collection, 7.3% (n=31) felt uncomfortable with the procedure, and 9.7% (n=41) reported some pain. The majority would recommend the procedure to others (99%), 88.5% of the sampled population preferred the self-collected method, 4% preferred conventional cytology, and 7.3% were not sure. The reasons behind favoring the self-collected procedure included privacy (n= 149, 40.1%), comfort (n=110, 29.7%), easiness (n=52, 14%), reliability (n=46, 12.4%), and less painful (n=110, 29.7%). The percentage of HPV detection agreement between the self-collected and the healthcare professional-collected procedures was 98.99% (Cohen's Kappa=0.9774). CONCLUSION: Women living in low-income households in Bucaramanga, Colombia preferred the self-sampling procedure because it was easy to use, convenient, and private, resulting in 98% acceptability, and positioning it as an excellent tool for CC prevention.
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Specimens of the African snail Achatina fulica, collected in Bucaramanga, Colombia, were examined for parasites. Numerous specimens of Caenorhabditis briggsae were collected from the digestive tract of the snails and identified by the structure of male spiculum, caudal bursa, gubernaculum and precloacal lip in males, triangular tooth in metarhabdion, and protandrous hermaphrodites with a female:male ratio of 15:1 and with morphometry. DNA sequences of the ITS2 region of the ribosomal gene array from worms in this study matched with 99% similarity to published sequences of C. briggsae. A redescription of the species is provided. This is the first record of the species in South America.
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Caenorhabditis/isolamento & purificação , Caramujos/parasitologia , Animais , Caenorhabditis/anatomia & histologia , Caenorhabditis/genética , Código de Barras de DNA Taxonômico , DNA de Helmintos/química , DNA de Helmintos/genética , DNA de Helmintos/isolamento & purificação , DNA Intergênico/química , DNA Intergênico/genética , Feminino , Larva/anatomia & histologia , Masculino , Reação em Cadeia da PolimeraseRESUMO
El cáncer de cuello uterino es causado por la infección persistente del epitelio cervical con los genotipos de alto riesgo del Virus del Papiloma Humano. Para su detección se realizan pruebas moleculares que detectan el gen L1 del VPH. Este gen puede perderse hasta en el 11 % de los casos durante la integración del ADN viral en el genoma del hospedero originando falsos negativos. Por otra parte, el oncogén E7 se expresa durante todas las etapas de progresión de la enfermedad. El objetivo de este trabajo fue estandarizar una PCR en tiempo real del oncogén E7 (E7-qPCR) para genotipificación y cuantificación de 6 VPH-AR. Los resultados muestran que la E7- qPCR amplificó VPH-16, -18, -31, -33, -35 y -45 con una alta sensibilidad con límites de detección desde 102 copias, eficiencias entre 90 y 110 %, valores R2 > 0,97 y análisis de curva de fusión que revelan productos específicos.
Cervical cancer is caused by persistent infection of the cervical epithelium with the high-risk genotypes of the Human Papilloma Virus (HR-HPV). For its detection, molecular tests are carried out that detect the L1 gene of HPV. This gene can be lost in up to 11 % of cases during the integration of viral DNA into the host genome, causing false negatives. On the other hand, the E7 oncogene is expressed during all stages of disease progression. The aim of this work was to standardize a real-time PCR of the E7 oncogene (E7-qPCR) for genotyping and quantification of 6 HR-HPV. The results show that the E7-qPCR amplified HPV-16, -18, -31, -33, -35 and -45 with high sensitivity with detection limits from 102 copies, efficiencies between 90 and 110 %, R2 values >0,97 and melting curve analysis revealing specific products.
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Humanos , Neoplasias do Colo do Útero , Infecções por Papillomavirus , Reação em Cadeia da Polimerase em Tempo Real , Papillomaviridae , Oncogenes , Técnicas de GenotipagemRESUMO
Introducción: Existen pocos reportes que evalúen la seroprevalencia contra SARS-CoV-2 en población migrante en el mundo. Estos estudios ayudan a conocer la exposición al virus en las poblaciones para implementar acciones que reduzcan el impacto de la infección por SARS-CoV-2. Objetivo: Determinar la seroprevalencia contra SARS CoV-2 en migrantes con vocación de permanencia en Bucaramanga, e identificar factores asociados a la infección previa por SARS-CoV-2. Materiales y métodos: Estudio de corte transversal analítico con muestreo consecutivo. Se incluyeron migrantes adultos en Bucaramanga durante febrero/2021. Se realizaron encuestas e inmunoensayos de quimioluminiscencia para IgM e IgG contra SARS-CoV-2 en suero. Se calcularon razones de prevalencia (RP) con regresión log-binomial. Resultados:Se incluyeron 462 participantes. La seroprevalencia de IgM fue 11,7% (IC95% 9,114,9), de IgG fue 32,9% (IC95% 28,837,3) y de IgM o IgG fue 36,1% (IC95% 31,9-40,6). Exposición a un caso confirmado (RP:1,54; IC95%1,04-2,29) o sospechoso (RP:1,56; IC95%1,13-2,16) de COVID-19, seis o más convivientes (RP:1,52; IC95%1,05-2,20), estancia en Colombia ≥2 años (RP:1,43; IC95%1,11-1,92) y presencia de síntomas (RP:1,62; IC95%1,26 - 2,10) se asociaron con mayor seroprevalencia de IgG. Discusión:En Bucaramanga, la seroprevalencia en migrantes fue similar a la de migrantes en Kuwait, pero menor que en Paris y Singapur. Conclusión: En migrantes con vocación de permanencia la seroprevalencia contra SARS-CoV-2 fue similar a la reportada en residentes de Bucaramanga. El contacto con casos sospechosos/confirmados de COVID-19 y las condiciones de hacinamiento fueron algunos de los factores asociados a la seroprevalencia.
Introduction:There are few reports assessing anti-SARS-CoV-2 seroprevalence in the migrant population in the world. These studies help to understand the exposure of populations to the virus to take actions to reduce the impact of SARS-CoV-2 infection. Objetive: To determine the anti-SARS-CoV-2 seroprevalence in migrants with a vocation for permanence in Bucaramanga and to identify factors associated with previous SARS-CoV-2 infection. Materials and Methods:Analytical cross-sectional study using consecutive sampling, which included adult migrants in Bucaramanga in February 2021. Surveys were conducted, and chemiluminescent immunoassays were performed to detect IgM and IgG antibodies to SARS-CoV-2 in serum samples. Prevalence ratios (PR) were estimated using a log-binomial regression model. Results:The study enrolled 462 participants. IgM seroprevalence was 11.7% (95% CI 9.114.9), IgG seroprevalence was 32.9% (95% CI 28.837.3), and IgM or IgG seroprevalence was 36.1% (95% CI 31.940.6). Contact with a confirmed case of COVID-19 (PR:1.54; 95% CI 1.04-2.29) or suspected case (PR:1.56; 95% CI 1.132.16); living with six or more people (PR: 1.52; 95% CI 1.052.20); stay in Colombia ≥ 2 years (PR:1.43; 95% CI 1.111.92), and presence of symptoms (PR:1.62; 95%CI 1.262.10) were some factors associated with higher IgG seroprevalence. Discussion: In Bucaramanga, SARS-CoV-2 seroprevalence among migrants was similar to the seroprevalences of migrants in Kuwait but lower than migrants in Paris and Singapore. Conclusions: The anti-SARS-CoV-2 seroprevalence among migrants with a vocation for permanence was similar to that reported among residents of Bucaramanga. Contact with suspected or confirmed COVID-19 cases and crowded conditions were some of the factors associated with seroprevalence.
Introdução: Existem poucos relatos que avaliam a soroprevalência contra SARS-CoV-2 na população migrante no mundo. Esses estudos ajudam a conhecer a exposição ao vírus nas populações para implementar ações que reduzam o impacto da infecção por SARS-CoV-2. Objetivo: Determinar a soroprevalência contra SARS CoV-2 em migrantes que pretendem permanecer em Bucaramanga e identificar fatores associados à infecção anterior por SARS-CoV-2. Materiais e Métodos: Estudo analítico transversal com amostragem consecutiva. Foram incluídos migrantes adultos em Bucaramanga durante fevereiro/2021. Foram realizados levantamentos e imunoensaios de quimioluminescência para IgM e IgG contra SARS-CoV-2 no soro. As razões de prevalência (RP) foram calculadas com regressão log-binomial. Resultados: foram incluídos 462 participantes. A soroprevalência de IgM foi de 11,7% (IC 95% 9,1-14,9), de IgG foi de 32,9% (IC 95% 28,8-37,3) e de IgM ou IgG foi de 36,1% (IC95% 31,9-40,6). Exposição a um caso confirmado (RP: 1,54; IC 95% 1,04-2,29) ou caso suspeito (RP: 1,56; IC 95% 1,13-2,16) de COVID-19, seis ou mais coabitantes (RP: 1,52; IC 95% 1,05 -2,20), permanência na Colômbia ≥2 anos (RP: 1,43; IC 95% 1,11-1,92) e presença de sintomas (RP: 1,62; IC95%1,26 - 2,10) foram associados a maior soroprevalência de IgG. Discussão: Em Bucaramanga, a soroprevalência em migrantes foi semelhante à de migrantes no Kuwait, mas menor do que em Paris e Cingapura. Conclusão: Em migrantes com vocação de permanência, a soroprevalência contra SARS-CoV-2 foi semelhante à relatada em residentes de Bucaramanga. O contato com casos suspeitos/confirmados de COVID-19 e as condições de superlotação foram alguns dos fatores associados à soroprevalência.
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Migrantes , Estudos Soroepidemiológicos , SARS-CoV-2RESUMO
Resumen Los interferones (IFNs) son citoquinas fundamentales en la modulación de la inmunidad innata y adaptativa del hospedero, el papel de los IFNs tipo I en el control de la infección por el Virus del Papiloma Humano (VPH) es crucial para una eficiente respuesta antiviral del huésped. Esta revisión profundiza sobre las funciones de los IFNs tipo I en la infección causada por el VPH y los mecanismos de evasión de este virus para inactivar los IFNs tipo I, todos estos mecanismos necesarios para el desarrollo y progresión de lesiones malignas en los tejidos infectados por el VPH.
Abstract The interferons (IFNs) are very important cytokines in the interface between innate and adaptive immunity of the host, the role type I IFNs in the control of HPV is pivotal for an efficient immune response, so a wide knowledge about this topic will contribute understanding HPV pathogenicity mechanism. This review focuses on the HPV evasion mechanisms for the type I IFNs which are necessary for a malignant lesion development, otherwise develops knowledge about the type I IFNs functions on the HPV infection.
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Humanos , Feminino , Interferon Tipo I , Neoplasias do Colo do Útero , Papillomaviridae , Colo do Útero , Sistema ImunitárioRESUMO
Resumen El 31 de diciembre de 2019 la comisión municipal de salud de Wuhan (provincia de Hubei, China) informa sobre un inusitado brote de casos de neumonía en la ciudad. Posteriormente se determina que se trata de un nuevo coronavirus designado inicialmente como 2019-nCoV y posteriormente, SARS-CoV-2. El SARS-CoV-2 infecta y se replica en los neumocitos y macrófagos del sistema respiratorio específicamente en el parénquima pulmonar en donde reside el receptor celular ACE-2. Esta revisión describe aspectos relacionados con la transmisión, prevención, generalidades bioquímicas del SARS-CoV-2 y métodos diagnósticos del COVID-19. Inicialmente se describe la forma de transmisión del virus y algunas recomendaciones generales para su prevención. Posteriormente, se hace una descripción detallada de los aspectos bioquímicos del SARS-CoV-2, su ciclo infeccioso y la estructura de la proteína S, la cual está involucrada con el proceso de ingreso del virus a la célula. Finalmente, se describen los métodos y pruebas de laboratorio para el diagnóstico del COVID-19.
Abstract On December 31, 2019, Wuhan Municipal Health Commission (Hubei Province, China) reports on an unusual outbreak of pneumonia cases in the city. Subsequently it is determined that it is a new coronavirus initially designated as 2019-nCoV and later, SARS-CoV-2. SARS-CoV-2 infects and replicates in pneumocytes and macrophages of the respiratory system specifically in the lung parenchyma where the ACE-2 cell receptor resides. This review describes aspects related to the transmission, prevention, biochemical generalities of SARS-CoV-2 and diagnostic methods of COVID-19. Initially, it describes the form of virus transmission and general recommendations for its prevention. Subsequently, a detailed description is made of the biochemical aspects of SARS-CoV-2, its infectious cycle and the structure of protein S, which is involved in the process of entry of the virus into the cell. Finally, the methods and laboratory tests for the diagnosis of COVID-19 are described.
Assuntos
Humanos , Coronavirus , Células Epiteliais Alveolares , Tecido Parenquimatoso , MacrófagosRESUMO
Persistent infection with human papillomavirus (HPV) induces cervical cancer. Here, we describe a sensitive, specific, and rapid assay for high-risk HPV16 and 18 detection by isothermal helicase-dependent amplification. This method can be used as cost-effective diagnostic method for low-income countries, where highest incidences worldwide of cervical cancer are registered.
Assuntos
Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Programas de Rastreamento/métodos , Sensibilidade e Especificidade , TemperaturaRESUMO
Introducción: Infección persistente con el virus de papiloma humano de alto riesgo (VPH-AR) causa cáncer de cuello uterino (CCU). Existen ensayos moleculares para la detección y la genotipificación del gen L1 de VPH, sin embargo, L1 puede perderse durante la integración viral. La expresión e integración del oncogén E7 es fundamental para el desarrollo de CCU. Objetivo: Estandarizar una PCR multiplex (mPCR) del oncogén E7 (E7-mPCR) para genotipificación de los VPH-AR de mayor frecuencia en CCU (VPH-16, -18, -31, -33, -45 y -52). Métodos: Se obtuvieron cepillados cervicales de voluntarias y se analizaron amplificando por PCR el gen L1 con subsecuente hibridación reversa. Posteriormente, se escogieron 59 muestras positivas para VPH-AR y se analizaron por E7-mPCR. Resultados: Se evidenció una elevada concordancia entre los resultados del ensayo E7-mPCR y los de la PCR de L1 (concordancia observada de 95,1 %, Kappa de Cohen = 0,88), encontrándose mayor número de infecciones por VPHAR en el 15,8 % con E7-mPCR. Conclusión: E7-mPCR es una herramienta diagnóstica con alta concordancia y económica que puede adaptarse a una plataforma de mayor complejidad para procesar y detectar mayor cantidad de muestras y genotipos de VPH-AR.
Introduction: Persistent infection with high-risk human papillomavirus (HR-HPV) causes cervical cancer (CCU). Molecular assays exist for detection and genotyping of the HPV L1 gene, however, L1 can be lost during viral integration. The expression and integration of the E7 oncogene is critical for the development of CCU. Objective: To standardize a multiplex PCR (mPCR) of the E7 oncogene (E7-mPCR) for genotyping the most frequent HR-HPVs in CCU (HPV-16, -18, -31, -33, -45 and -52). Methods: Cervical brushings were obtained from volunteers and analyzed by PCR amplification of the L1 gene with subsequent reverse hybridization. Subsequently, 59 HR-HPV-positive samples were selected and analyzed by E7-mPCR. Results: There was a high concordance between E7-mPCR and L1 PCR results (observed concordance 95.1 %, Cohen's Kappa = 0.88), with a higher number of HR-HPV infections found in 15.8 % with E7-mPCR. Conclusion: E7-mPCR is a highly concordant and cost-effective diagnostic tool that can be adapted to a more complex platform to process and detect a larger number of HR-HPV samples and genotypes.
Introdução: A infeção persistente pelo papilomavírus humano de alto risco (HR-HPV) causa cancro do colo do útero (CCU). Existem ensaios moleculares para a deteção e genotipagem do gene L1 do HPV, no entanto, o L1 pode perder-se durante a integração viral. A expressão e integração do oncogene E7 é fundamental para o desenvolvimento do CCU. Objetivo: Padronizar uma PCR multiplex (mPCR) do oncogene E7 (E7-mPCR) para genotipar os HR-HPVs mais frequentes no CCU (HPV-16, -18, -31, -33, -45 e -52). Métodos: Foram obtidas escovagens cervicais de voluntárias e analisadas por amplificação por PCR do gene L1 com subsequente hibridação inversa. Subsequentemente, foram seleccionadas 59 amostras HR-HPV-positivas e analisadas por E7-mPCR. Resultados: Verificou-se uma elevada concordância entre os resultados da E7-mPCR e da L1 PCR (concordância observada de 95,1 %, Cohen's Kappa = 0,88), com um número mais elevado de infecções por HR-HPV detectadas em 15,8 % com a E7-mPCR. Conclusão: A E7-mPCR é uma ferramenta de diagnóstico altamente concordante e económica que pode ser adaptada a uma plataforma mais complexa para processar e detetar um maior número de amostras e genótipos de HR-HPV.
Assuntos
HumanosRESUMO
Introducción: Infección persistente con el virus de papiloma humano de alto riesgo (VPH-AR) causa cáncer de cuello uterino (CCU). Existen ensayos moleculares para la detección y la genotipificación del gen L1 de VPH, sin embargo, L1 puede perderse durante la integración viral. La expresión e integración del oncogén E7 es fundamental para el desarrollo de CCU. Objetivo: Estandarizar una PCR multiplex (mPCR) del oncogén E7 (E7-mPCR) para genotipificación de los VPH-AR de mayor frecuencia en CCU (VPH-16, -18, -31, -33, -45 y -52). Métodos: Se obtuvieron cepillados cervicales de voluntarias y se analizaron amplificando por PCR el gen L1 con subsecuente hibridación reversa. Posteriormente, se escogieron 59 muestras positivas para VPH-AR y se analizaron por E7-mPCR. Resultados: Se evidenció una elevada concordancia entre los resultados del ensayo E7- mPCR y los de la PCR de L1 (concordancia observada de 95,1%, Kappa de Cohen = 0,88), encontrándose mayor número de infecciones por VPH- AR en el 15,8% con E7-mPCR. Conclusión: E7-mPCR es una herramienta diagnóstica con alta concordancia y económica que puede adaptarse a una plataforma de mayor complejidad para procesar y detectar mayor cantidad de muestras y genotipos de VPH-AR.
Introduction: The persistent infection of the high-risk Human Papiloma Virus (VPH-AR in Spanish) causes uterine cervix cancer (CCU in Spanish). There are molecular essays for detection and genotyping of gen L1 of VPH. However, L1 may get lost during the viral integration. The expression and integration of oncogene E7 is fundamental for the development of CCU. Objective: To standardize a multiplex PCR (mPCR) of oncogene E7 (E7-mPCR) for genotyping the VPH- AR of highest frequency in CCU (VPH-16, -18, -31, -33, -45 y -52). Method: We obtained cervix brushing simples from volunteers and we analyzed them by amplifying the L1 gene through PCR with a subsequent reverse hybridization. After that, we chose 59 positive VPH- AR samples and we analyzed them for E7-mPCR. Results: We found out a high concordance between the results of the essay E7-mPCR and those of L1 PC (Observed concordance was of 95.1%, Cohen's Kappa = 0.88), and we revealed a higher number of infections for VPH-AR in a 15.8% with E7-mPCR. Conclusion: E7-mPCR is an economic diagnostic tool with high concordance which can be adapted to a platform with more complexity to process and detect a higher number of samples and VPH-AR genotypes.
Introdução: a infecção persistente com o virus de papiloma humano de alto risco (HPV-AR) causa cáncer de colo do útero (CCU). Existem ensaios moleculares para detecção e para a genotipificação do gene L1 de HPV; contudo, L1 pode ser perdido durante a integrado viral. A expressão e integração do oncogênese E7 é fundamental para o desenvolvimento do CCU. Objetivo: padronizar uma PCR multiplex (mPCR) do oncogênese E7 (E7-mPCR) para genotipificação dos HPV-AR de maior frequência no CCU (HPV-16, -18, -31, -33, -45 e -52). Métodos: foram realizadas raspagens com escova cervical rodada em voluntárias e foram analisadas a partir da amplificação do gene L1 por PCR com subsequente hibridação inversa. Em seguida, foram escolhidas 59 amostras positivas para HPV-AR, as quais foram analisadas por E7-mPCR. Resultados: foi evidenciada elevada concordância entre os resultados do ensaio E7-mPCR e os da PCR de L1 (concordância observada de 95,1%, Kappa de Cohen = 0,88), encontrando-se maior número de infecções por HPV-AR em 15,8% com E7-mPCR. Conclusão: E7-mPCR é uma ferramenta diagnóstica com alta concordância e económica que pode ser adaptada a uma plataforma de maior complexidade para processar e detectar maior quantidade de amostras e genótipos de HPV-AR.
RESUMO
Resumen Introducción: Para el desarrollo de cáncer de cuello de uterino la infección con el Virus de Papiloma Humano (VPH) es una causa necesaria. Sin embargo, la eliminación viral está asociada a múltiples factores, algunos modificables y otros no, que varían según las características poblacionales y áreas geográficas. Objetivo: Determinar factores asociados a la prevalencia de infección por virus de Papiloma Humano de alto riesgo en mujeres entre 35-65 años con riesgo moderado o alto de cáncer de cuello uterino de la zona norte de Bucaramanga. Metodología: Estudio analítico de corte transversal. A las mujeres clasificadas como de moderado/alto riesgo para cáncer de cuello uterino en una encuesta corta estandarizada, se les realizó una encuesta sobre factores potenciales asociados a infección, seguida de una autónoma de muestra cervical, que se utilizó para detección de DNA viral. Se realizó análisis múltiple de regresión log-binomial para obtener Razones de Prevalencia ajustadas (RPa). Resultados: Se entrevistaron 810 mujeres, de éstas 435 tuvieron moderado/alto riesgo para cáncer y se realizaron la autotoma. La prevalencia de infección por VPH de alto riesgo fue de 5,1% (IC 95% 3,2-7,6). El sedentarismo (RPa 2,51; IC95% 1,15-5,50) y el sobrepeso/obesidad (PRa 4,20; IC95% 1,00-15,51) se asociaron a mayor prevalencia. Además, hubo una tendencia de incremento en la prevalencia de infección en las usuarias de anticonceptivos inyectables; así como una tendencia de disminución de esta prevalencia según porciones de frutas y verduras consumidas diariamente. Conclusión: Factores modificables como sedentarismo y sobrepeso/obesidad, se asociaron independientemente a mayor prevalencia de infección por VPH en la población estudiada.
Abstract Introduction: Infection with Human Papillomavirus is mandatory for cervical cancer development. However, viral elimination is associated to multiple factors, according to the population characteristics and geographic areas, some are modifiable and others not. Objective: To determine the factors associated with the prevalence of high risk human papillomavirus infection in women between 35-65 years old with moderate or high risk of cervical cancer located at the northern zone of Bucaramanga. Methodology: Cross-sectional analytical study. Women classified as moderate/ high risk for cervical cancer in a short standardized survey, were surveyed on the side effects associated to chronic viral infection and self-sampling cervical test. Bivariate analysis and multiple analysis of log-binomial regression were performed. Results: 810 women were interviewed; 435 cases of high cancer risk were presented. The prevalence of high risk human papilloma virus infection was 5.1% (95% CI 3.2-7.6). The sedentary lifestyle (RPa 2.51, 95% CI 1.15-5.50) and overweight/obesity (PRa 4.20, 95% CI 1.00-15.51) were associated with higher prevalence. In addition, there was a trend of increased prevalence of infection among users of injectable contraceptives; as well as a tendency to decrease this prevalence according to portions of fruits and vegetables consumed daily. Conclusion: modifiable factors such as sedentary lifestyle and overweight / obesity were independently associated with a higher prevalence of infection by human high risk papilloma virus in the population studied.