Salvador Fonseca-Coronado

Norovirus (NoV) es uno de los principales agentes etiológicos de gastroenteritis aguda en humanos y animales. Es un virus altamente infeccioso y de distribución mundial. La infección se realiza a través de la interacción con receptores HBGA, presentes en diferentes células epiteliales superficiales y en fluidos corporales de humanos, murinos, bovinos y murciélagos. Estos receptores también están presentes en las células epiteliales intestinales (enterocitos) de los conejos, razón por la cual se favorece la infección por NoV. La cunicultura en México surge como alternativa a la escasez de alimentos y la falta de empleo en las zonas rurales, por ello es importante apoyar en el fortalecimiento de la actividad. El objetivo de esta investigación consistió en detectar infecciones producidas por NoV en los conejos en unidades de producción cunícola del Estado de México, mediante la técnica de RT-PCR. Como resultado obtuvimos una frecuencia de 22.34% de NoV presente en conejos con signología diarreica. Estos resultados nos dan la pauta para continuar con el estudio de NoV en conejos y poder evaluar su posible potencial zoonótico que contribuya al conocimiento del estado zoosanitario y además permita la mejora en la salud pública de la población.

Rotavirus species A (RVA) is a major cause of acute viral gastroenteritis in young humans and diverse animal species. The study of the genetic characteristics of RVAs that infect rabbits (Oryctolagus cuniculus) (lapine strain [LRV]) has been limited, and, to date, the most common and epidemiologically important combinations of G/P genotypes in rabbits have been reported to be G3 P[14] and G3 P[22]. In this study, a rotavirus species A detected from an outbreak of enteritis in a Mexican commercial rabbitry was genotypically characterized. Based on sequence and phylogenetic analysis of the VP7 and VP4 genes, the strain identified in this study (C-3/15) demonstrated a G3 P[8] genotype of rotavirus, which had not previously been reported in rabbits. Moreover, both genes were closely related to human, not lapine, rotaviruses. The G3 genotype has been reported in a wide variety of hosts, including humans and rabbits, whereas the P[8] genotype has only been reported in humans. Because this combination of genotypes has never been identified in rabbits, it is proposed that the finding presented here is possibly the result of an interspecies transmission event. This is the first work to study the molecular characteristics of rotaviruses in rabbits in Mexico, as well as the identification of human G3 and P[8] genotypes in a rabbit with enteric disease.

Antihypertensive drug therapies have demonstrated their capacity to modulate the inflammatory processes associated with hypertension, leading to improvements in disease progression. Given the prevalent use of polytherapy in treating most hypertensive patients, comprehending the time‐dependent effects of combination treatments on inflammation becomes imperative. In this study, spontaneously hypertensive rats (SHR) were divided into seven groups (n = 6): (i) SHR + vehicle, (ii) SHR + nebivolol, (iii) SHR + valsartan, (iv) SHR + lisinopril, (v) SHR + nebivolol–valsartan, (vi) SHR + nebivolol–lisinopril, and (vii) WKY + vehicle. Blood pressure was measured using the tail‐cuff method. Temporal alterations in inflammatory cytokines TNF‐α, IL‐6, and IL‐10 were assessed in serum through ELISA and mRNA expression in aortic tissue via qPCR after 1, 2, and 4 weeks of treatment with nebivolol, lisinopril, valsartan, and their respective combinations. Histological alterations in the aorta were assessed. The findings indicated that combined treatments reduced systolic and diastolic blood pressure in SHR. The nebivolol and lisinopril combination demonstrated a significant decrease in IL‐6 serum and mRNA expression at both 1 week and 4 weeks into the treatment. Additionally, TNF‐α mRNA expression also showed a reduction with this combination at the same time points. Particularly, nebivolol–valsartan significantly decreased TNF‐α serum and mRNA expression after one and four weeks of treatment. Furthermore, an elevation in serum IL‐10 levels was observed with both combination treatments starting from the second week onwards. This study provides compelling evidence that concurrent administration of nebivolol with lisinopril or valsartan exerts time‐dependent effects, reducing proinflammatory cytokines TNF‐α and IL‐6 while modifying IL‐10 levels in an experimental hypertensive model.

Cardiovascular disease incidence increases after menopause due to the loss of estrogen cardioprotective effects. However, there are conflicting data regarding the timing of estrogen therapy (ERT) and its effect on vascular dysfunction associated with impaired glucose metabolism. The aim of this work was to evaluate the effect of early and late ERT on blood glucose/insulin balance and vascular reactivity in aged ovariectomized Wistar rats. Eighteen-month-old female Wistar rats were randomized as follows: (1) sham, (2) 10-week postovariectomy (10 w), (3) 10 w postovariectomy+early estradiol therapy (10 w-early E2), (4) 20-week postovariectomy (20 w), and (5) 20-week postovariectomy+late estradiol therapy (20 w-late E2). Early E2 was administered 3 days after ovariectomy and late therapy after 10 weeks, in both groups. 17β-Estradiol (E2) was administered daily for 10 weeks (5μg/kg/day). Concentration-response curves to angiotensin II, KCl, and acetylcholine (ACh) were performed. Heart rate (HR), diastolic and systolic blood pressure (DBP and SBP), glucose, insulin, HOMA-IR, and nitric oxide (NO) levels were determined. Higher glucose levels were found in all groups compared to the sham group, except the 20 w-late E2 group. Insulin was increased in all ovariectomized groups compared to sham. The HOMA-IR index showed insulin resistance in all ovariectomized groups, except for the 10 w-early E2 group. The 10 w-early E2 group increased NO levels vs. the 10 w group. After 10 w postovariectomy, the vascular response to KCl and Ach increases, despite early E2 administration. Early and late E2 treatment decreased vascular reactivity to Ang II. At 20-week postovariectomy, DBP increased, even with E2 administration, while SBP and HR remained unchanged. The effects of E2 therapy on blood glucose/insulin balance and vascular reactivity depend on the timing of therapy. Early ERT may provide some protective effects on insulin resistance and vascular function, whereas late ERT may not have the same benefits.

Mycobacterium tuberculosis is an acid-fast bacterium that causes tuberculosis worldwide. The role of epistatic interactions among different loci of the M. tuberculosis genome under selective pressure may be crucial for understanding the disease and the molecular basis of antibiotic resistance acquisition. Here, we analyzed polymorphic loci interactions by applying a model-free method for epistasis detection, SpydrPick, on a pan–genome-wide alignment created from a set of 254 complete reference genomes. By means of the analysis of an epistatic network created with the detected epistatic interactions, we found that glgB (α-1,4-glucan branching enzyme) and oppA (oligopeptide-binding protein) are putative targets of co-selection in M. tuberculosis as they were associated in the network with M. tuberculosis genes related to virulence, pathogenesis, transport system modulators of the immune response, and antibiotic resistance. In addition, our work unveiled potential pharmacological applications for genotypic antibiotic resistance inherent to the mutations of glgB and oppA as they epistatically interact with fprA and embC, two genes recently included as antibiotic-resistant genes in the catalog of the World Health Organization. Our findings showed that this approach allows the identification of relevant epistatic interactions that may lead to a better understanding of M. tuberculosis by deciphering the complex interactions of molecules involved in its metabolism, virulence, and pathogenesis and that may be applied to different bacterial populations.

Objectives To analyze the role of viral infections as etiology of stillbirths in Mexico and their epidemiological impact in the context of the global Every Newborn Initiative. Methods A comprehensive literature search was performed in electronic databases related to stillbirth and viral infections published prior to January 19th 2021. Stillbirths records and causes from National Mexican databases, during 2008–2019 period were also computed. Results Only two articles with a direct relationship between viral infection and stillbirth were found, and one article with an indirect serological association was identified. During the analyzed period there were 198,076 stillbirths, with a National stillbirth rate (SBR) ranging from 6.9 to 6.5 between 2008 and 2014, with a subsequent increase to reach 7.7 in 2019. Only 19 cases were attributed to viral causes and a specific virus was identified in 11. The main causes of early stillbirth were a fetus with premature rupture of membranes and light for gestational age, and for late stillbirth these were fetus affected by oligohydramnios and slow fetal growth. The percentage classified as unspecified deaths varied from 34.4-41.9%. Conclusions In Mexico, there has been an increase in SBR during last years, but the goals of the Every Newborn Initiative is met. More than 14,500 stillbirths with at least 5,100 unspecified cases have been reported per year, and only 11 cases were attributable to a specific virus, highlighting the serious underestimation of cases and the need of implementation of routine viral diagnosis methods to improve the care of this global health problem.

Identifying the Mycobacterium tuberculosis resistance mutation patterns is of the utmost importance to assure proper patient’s management and devising of control programs aimed to limit spread of disease. Zoonotic Mycobacterium bovis infection still represents a threat to human health, particularly in dairy production regions. Routinary, molecular characterization of M. bovis is performed primarily by spoligotyping and mycobacterial interspersed repetitive units (MIRU) while next generation sequencing (NGS) approaches are often performed by reference laboratories. However, spoligotyping and MIRU methodologies lack the resolution required for the fine characterization of tuberculosis isolates, particularly in outbreak settings. In conjunction with sophisticated bioinformatic algorithms, whole genome sequencing (WGS) analysis is becoming the method of choice for advanced genetic characterization of tuberculosis isolates. WGS provides valuable information on drug resistance and compensatory mutations that other technologies cannot assess. Here, we performed an analysis of the most frequently identified mutations associated with tuberculosis drug resistance and their genetic relationship among 2,074 Mycobacterium bovis WGS recovered primarily from non-human hosts. Full-length gene sequences harboring drug resistant associated mutations and their phylogenetic relationships were analyzed. The results showed that M. bovis isolates harbor mutations conferring resistance to both first- and second-line antibiotics. Mutations conferring resistance for isoniazid, fluoroquinolones, streptomycin, and aminoglycosides were identified among animal strains. Our findings highlight the importance of molecular surveillance to monitor the emergence of mutations associated with multi and extensive drug resistance in livestock and other non-human mammals.