Microbiome in the nasopharynx: Insights into the impact of COVID-19 severity.

Background: The respiratory tract harbors a variety of microbiota, whose composition and abundance depend on specific site factors, interaction with external factors, and disease. The aim of this study was to investigate the relationship between COVID-19 severity and the nasopharyngeal microbiome. Methods: We conducted a prospective cohort study in Mexico City, collecting nasopharyngeal swabs from 30 COVID-19 patients and 14 healthy volunteers. Microbiome profiling was performed using 16S rRNA gene analysis. Taxonomic assignment, classification, diversity analysis, core microbiome analysis, and statistical analysis were conducted using R packages. Results: The microbiome data analysis revealed taxonomic shifts within the nasopharyngeal microbiome in severe COVID-19. Particularly, we observed a significant reduction in the relative abundance of Lawsonella and Cutibacterium genera in critically ill COVID-19 patients (p < 0.001). In contrast, these patients exhibited a marked enrichment of Streptococcus, Actinomyces, Peptostreptococcus, Atopobium, Granulicatella, Mogibacterium, Veillonella, Prevotella_7, Rothia, Gemella, Alloprevotella, and Solobacterium genera (p < 0.01). Analysis of the core microbiome across all samples consistently identified the presence of Staphylococcus, Corynebacterium, and Streptococcus. Conclusions: Our study suggests that the disruption of physicochemical conditions and barriers resulting from inflammatory processes and the intubation procedure in critically ill COVID-19 patients may facilitate the colonization and invasion of the nasopharynx by oral microorganisms.

Development of Luminescent Biosensors for Calprotectin.

Calprotectin, a metal ion-binding protein complex, plays a crucial role in the innate immune system and has gained prominence as a biomarker for various intestinal and systemic inflammatory and infectious diseases, including inflammatory bowel disease (IBD) and tuberculosis (TB). Current clinical testing methods rely on enzyme-linked immunosorbent assays (ELISAs), limiting accessibility and convenience. In this study, we introduce the Fab-Enabled Split-luciferase Calprotectin Assay (FESCA), a novel quantitative method for calprotectin measurement. FESCA utilizes two new fragment antigen binding proteins (Fabs), CP16 and CP17, that bind to different epitopes of the calprotectin complex. These Fabs are fused with split NanoLuc luciferase fragments, enabling the reconstitution of active luciferase upon binding to calprotectin either in solution or in varied immobilized assay formats. FESCA's output luminescence can be measured with standard laboratory equipment as well as consumer-grade cell phone cameras. FESCA can detect physiologically relevant calprotectin levels across various sample types, including serum, plasma, and whole blood. Notably, FESCA can detect abnormally elevated native calprotectin from TB patients. In summary, FESCA presents a convenient, low-cost, and quantitative method for assessing calprotectin levels in various biological samples, with the potential to improve the diagnosis and monitoring of inflammatory diseases, especially in at-home or point-of-care settings.

The rs11684747 and rs55790676 SNPs of ADAM17 influence tuberculosis susceptibility and plasma levels of TNF, TNFR1, and TNFR2.

Introduction: The proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation. Methods: Here, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models. Results: Our results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts. Conclusion: These findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.

Winds of change a tale of: asthma and microbiome.

The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome's role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus, and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches.

Epigenetics in non-small cell lung carcinomas / Epigenetica en carcinomas pulmonares de células no pequeñas

Abstract: Objective: To perform a systematic review of the main epigenetic aberrations involved in non-small cell lung carcinomas' (NSCLC) diagnosis, progression, and therapeutics. Materials and methods: We performed a systematic review of the scientific literature on lung cancer epigenetics, focusing on NSCLC. Results: Several advances in the molecular study of classical epigenetic mechanisms and massive studies of lung cancer epigenome have contributed relevant new evidence revealing that various molecular complexes are functionally influencing genetic-epigenetic and transcriptional mechanisms that promote lung tumorigenesis (initiation, promotion, and progression), and are also involved in NSCLC therapy-resistance mechanisms. Conclusion: Several epigenetic complexes and mechanisms must be analyzed and considered for the design of new and efficient therapies, which could be fundamental to develop an integrated knowledge to achieve a comprehensive lung cancer personalized medicine.

Resumen: Objetivo: Realizar una revisión sistemática y estructurada de las principales aberraciones epigenéticas involucradas en el diagnóstico, progresión y terapia del cáncer pulmonar de células no pequeñas (CPCNP). Material y métodos: Revisión sistemática de literatura científica sobre epigenética del cáncer pulmonar del grupo CPCNP. Resultados: El estudio de los diversos mecanismos epigenéticos y su impronta epigenética en el epigenoma del cáncer pulmonar han arrojado nuevas evidencias a nivel biológico, biomédico y médico-clínico del impacto que los mecanismos epigenético-transcripcionales promueven de manera activa y reversible sobre los procesos de tumorigénesis, progresión histopatológica y mecanismos de resistencia a la terapia oncológica pulmonar. Conclusión: Deben analizarse diferentes complejos y mecanismos epigenéticos para el estudio y diseño de esquemas nuevos y eficaces de terapia epigenética, los cuales podrían ser fundamentales para desarrollar un conocimiento integral en el desarrollo de la medicina personalizada en el cáncer pulmonar del grupo CPCNP.

Cuerpos extraños en vía aerodigestiva en los niños. Experiencia de siete años, Hospital Universitario Erasmo Meoz / Foreign bodies in aerodigestive tract in children. Seven years series, Hospital Universitario Erasmo Meoz

Objetivo: Describir la población con ingesta de cuerpos extraños en vía digestiva y aérea, e identificar los métodos diagnósticos y tratamientos efectuados. Materiales y métodos: Se presenta un estudio descriptivo, retrospectivo de revisión de historias clínicas de pacientes pediátricos que ingresan por ingesta de cuerpo extraño tratados por el Servicio de Cirugía Pediátrica del Hospital Universitario Erasmo Meoz de Cúcuta, atendidos entre enero de 2000 y diciembre de 2007. Resultados: Se recopilan 158 eventos. Con mayor frecuencia de ingesta de cuerpos extraños en los hombres (70.9%). Se encontró el cuerpo extraño en el 97.5%, 72.8% en la vía digestiva, 23.4% en la vía aérea y 3.2% en cavidad bucal El sitio más frecuente en la vía digestiva fue el esófago proximal y en la vía aérea, el bronquio fuente derecho. Los cuerpos extraños más comúnmente encontrado fueron las monedas. Fueron sintomáticos el 93.7% de los pacientes, con sialorrea y vómito. Se utilizaron como métodos diagnósticos las radiografías de cuello, tórax y abdomen. Para la extracción se realizó endoscopia de vías digestivas altas en 54.7% de los pacientes; en los demás, según el caso se realizó broncoscopia o laringoscopia y extracción con pinza de MacGill. Conclusiones: La ingesta de cuerpos extraños en los niños es un evento común, por lo cual se debe tener conocimiento en cuanto al diagnóstico oportuno, manejo y prevención. Debemos reconocer su sintomatología para la rápida ejecución de la extracción, evitando así aumento de la morbilidad. [Trujillo ML, Villamizar JE. Cuerpos extraños en vía aerodigestiva en los niños. Experiencia de siete años, Hospital Universitario Erasmo Meoz. MedUNAB 2008; 11:195-200].

Objective: To describe eth infant and children population with foreign body in airway or digestive tract, and their diagnosis and treatment. Materials and methods: A descriptive, retrospective clinical record review was done, including all pediatric patients attended by foreign body ingestion history; all were treated in Pediatric Surgery Service, Hospital Universitario Erasmo Meoz, Cúcuta (Colombia), from January 2000 to December 2007. Results: 158 foreign body ingestion cases were detected; 70.9% were presented in male. In 97.5% a foreign body were found, 72.8% in digestive tract, 23.4% in airway, and 3.2% in mouth. The place most frequently affected were upper esophagus and right bronchus. Most saw foreign bodies were coins; 93.7% patients develop symptoms such as sialorrhea and vomiting. Neck, chest, and abdominal X-ray were diagnoses methods used, for treatment an extraction of foreign bodies, esophagogastroduodenoscopy, was performed in 54.7% of the patients; bronchoscopy or laringoscopy and extraction with MacGill forceps according to each case were also performed. Conclusions: Foreign body ingestion in is a very often event; it bind to have the knowledge about the opportune diagnose, treatment and prevention. We should recognize the symptoms arise to proceed quickly with the extraction to avoid increase of morbidity. [Trujillo ML, Villamizar JE. Foreign bodies in aerodigestive tract in children. Seven years series, Hospital Universitario Erasmo Meoz. MedUNAB 2008; 11:195-200].

Influencia de alelos y haplotipos del complejo principal de histocompatibilidad en la susceptibilidad a lupus eritematoso generalizado en la población mexicana / Influence of alleles and haplotypes of the main histocompatibility complex on the susceptibility to systemic lupus erythematosus in the Mexican population

A pesar de que se han asociado algunos alelos del complejo principal de histocompatibilidad (MHC) con la susceptibilidad a lupus eritematoso generalizado (LEG) en diferentes grupos étnicos, aún se desconoce la contribución de otros genes como los HSP70 y TNF-α en la susceptibilidad a esta enfermedad. Además, las asociaciones genéticas varían con base en el grupo étnico estudiado, lo que sugiere que la etnicidad tiene un papel importante en la susceptibilidad. En este estudio se analizaron las frecuencias de los genes HLA-DRB1, DQA1, DQB1, HSP70-2 y polimorfismos del promotor de TNF-α en 81 pacientes mexicanos con LEG. Como grupo control se estudiaron 99 sujetos mexicanos mestizos sanos. El haplotipo DRB1*0301- DQA1*0501-DQB1*0201 se asoció con LEG. El alelo DRB1*1501 se encontró con mayor frecuencia en los pacientes con LEG en comparación con los grupos control. Además se observó menor frecuencia de marcadores autóctonos como el alelo DRB1*0802 en los pacientes con LEG. Los alelos del MHC asociados con LEG son poco frecuentes en las poblaciones indígenas mexicanas. Esto podría sugerir que los marcadores de susceptibilidad a LEG se incorporaron a la población mestiza mexicana por flujo genético de poblaciones no indígenas.

HLA alelles with susceptibility to systemic lupus erythematosus (SLE) have been found in many ethnic groups. In addition, some neighboring genes such as TNF-alpha and HSP70, that may contribute to this disease have also been described. Interestingly some of the genetic associations differ among several ethnic groups, which might suggest that ethnicity plays an important role in the predisposition to SLE. In this study, we analyze gene frequencies of HLA-DRB1, DQA1, DQB1, HSP70-2 alelles and the polymorphism of TNF-alpha promoter region among 81 Mexican mestizo SLE patients. A control group of 99 healthy Mexican mestizos was included. We found that the HLA-DRB1*0301-DQA1*0501-DQB1*0201 haplotype was significantly increased in SLE patients compared to healthy controls (p=0.01, OR=2.97, IC 95%=1.18-7.68). The DRB1*1501 allele was more frequent among patients than among controls. A significantly decreased frequency of the HLA-DRB1*0802 alelle in SLE patients was also observed. Since the HLA alelles associated with SLE are uncommon in Mexican ethnic groups, we performed admixture estimates analysis and found that the incorporation of SLE susceptibility markers in Mexican mestizo groups might have come from genetic admixture with Caucasian populations.

Asociación del alelo HLA-DQB1*0501 del complejo mayor de histocompatibilidad con cáncer gástrico en México / Association of the HLA-DQB*0501, Allele of the major Histocompability Complex with Gastric Cancer in Mexico

El cáncer gástrico está relacionado con factor es ambientales y propios del huésped. La infección por Helicobacter pylori es un factor ambiental preponderante y se ha propuesto además que, algunos genes del complejo mayor de histocompatibilidad confieren susceptibilidad o resistencia para las enfermedades gástricas relacionadas con dicha infección. Con el propósito de conocer la distribución y frecuencia de algunos genes HLA-DQ del complejo mayor de histocompatibilidad en sujetos mexicanos con enfermedades gástricas, se estudiaron 20 pacientes con cáncer gástrico y 40 pacientes con gastritis crónica asociada con Helicobacter pylori. Los diagnósticos fueron confirmados con biopsias. Se utilizaron para fines comparativos, 99 individuos sanos. La genotipificación de los alelos HLA se realizó mediante la técnica de reacción en cadena de la polimerasa. Los pacientes con cáncer gástrico tuvieron mayor frecuencia de los alelos HLA-DQA1 *0601 (p = 0.003; RM = 20.9; LC 95% = 2.11-506.2) y HLA DQB 1*0501, éste último en comparación a los pacientes con gastritis crónica (p =0.04; RM = 3.58; LC 95 % = 1.05-12.5) e individuos sanos (p = 0.002; RM = 4.5; LC 95% = 1.59-12.7). En conclusión, nuestros resultados sugieren que además de la infección por Helicobacter pylori, hay marcadores de la región HLA-DQ que son determinantes inmunogenéticamente en la susceptibilidad para desarrollar cáncer gástrico.

Etiology of gastric cancer is related to environmental and host factors, Helicobacter pylori infection is the main environmental factor, but it has been also proposed that some major histocompatibility complex genes are related to susceptibility and resistance to develop Helicobacter pylori-as so dated gastric diseases. The aim of this study was to study distribution and frequency of some HLA-DQ genes, among Mexican patients harboring gastric diseases. We studied 20 subjects suffering from gastric cancer and 40 subjects harboring Helicobacter pylori-associated chronic gastritis. Diagnosis was confirmed by biopsy. HLA genotyping was performed by a polymerase chain reaction procedure. Ninety nine healthy individuals were also utilized for comparative purposes. Patients with gastric cancer displayed high frequency of HLA-DQA 1 *0601 (p = 0.003; OR = 20.9, 95% CL = 2.11-506.2) and HLA-DQB 1*0501 alleles, the latter when compared to patients with chronic gastritis (p = 0.04; OR = 3.58, 95% CL = 1.05-12.5) and to healthy individuals (p = 0.002; OR = 4.5, 95% CL =1.59-12.7). According to our results, in addition to Helicobacter pylori infection, there are immunogeneic markers of the HLA-DQ region, which are determinant in confering susceptibility for gastric cancer.

Artritis reumatoide de casos múltiples: estudio de una familia mexicana / Multiple rheumatoid arthritis. Study of one mexican family

La artritis reumatoide(AR) es una enfermedad inflamatoria crónica de etiología desconocida y en donde numerosos estudios han encontrado asociación con los genes clase I y clase II del complejo principal de histocompatibilidad (CPH), principalmente en los locus del HLA-B y el HLA-DR y el desarrollo de AR. En este reporte se estudió una familia mexicana con AR en donde 4 mujeres estaban afectadas. El haplotipo estrechamente estrechamente asociado con est enfermedad fue el HLA-A1, B5, DR4, DRB1*0404, DQ3, DRw53. En conclusión, estos resultados confirman el papael directo que tiene los genes calse II del CPH en la susceptibilidad al desarrollo de AR y se discute la gran heterogeneidad genética localizada en el locus HLA-B, la cual varía de acuerdo al grupo étnico que se estudie

Los factores genéticos determinantes de la resistencia a la infección por VIH y del control de la progresión al SIDA: Implicaciones sobre la patogénesis y las estrategias terapéuticas para la erradicación del VIH. Una revisión

Esta revisión describe y discute los factores genéticos que al menos en parte, determinan la resistencia a la infección y que controlan el curso progresivo de la enfermedad en las personas infectadas por el virus de la inmunodeficiencia humana. Los factores genéticos podrían explicar la no progresión o la progresión lenta de la enfermedad, de una proporción de individuos infectados por VIH denominados no progresores a largo plazo. En general, este grupo permanece sin síntomas durante más de 10 años, mantiene estable sus niveles circulantes de cT CD4+ y habitualmente tiene baja carga viral. No obstante que los fenómenos de la no progresión y de la progresión rápida son aún incomprendidos, es probable que ciertos alelos de clase I y clase II del complejo principal de histocompatibilidad se asocien con un riesgo menor o mayor para desarrollar el síndrome de inmunodeficiencia adquirida...